Conditions: Epithelial Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer
Keywords: Epithelial ovarian cancer Fallopian tube cancer Primary peritoneal cancer IMGN853 ADC Antibody drug conjugate ImmunoGen Antibody Phase 1 Folate receptor alpha Mirvetuximab
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 264
Healthy volunteers: no

Brief summary:
This study comprises a Dose Escalation phase followed by a Dose Expansion phase. Dose Escalation part of the study will assess the safety and tolerability and determine the maximum tolerated dose (MTD) as the recommended Phase 2 (RP2D) dose for each regimen. Participants will be assigned to one of the 4 regimens in Dose Escalation phase: Regimen A: mirvetuximab soravtansine administered with bevacizumab; Regimen B: mirvetuximab soravtansine administered with carboplatin; Regimen C: mirvetuximab soravtansine administered with pegylated liposomal doxorubicin; or Regimen D: mirvetuximab soravtansine administered with pembrolizumab. Dose Expansion of the study will further assess safety, tolerability and preliminary anti-tumor activity of mirvetuximab soravtansine. A Dose Expansion phase is planned for Regimen A and Regimen D and will open pending Sponsor decision; participants enrolled in the Dose Expansion phase will receive study treatment at the MTD or RP2D determined during Dose Escalation. For Regimen A, participants in the Dose Expansion phase may be enrolled according to prior exposure to bevacizumab into 3 Dose Expansion Cohorts as follows: 1) Dose Expansion Cohort 1: bevacizumab naïve; 2) Dose Expansion Cohort 2: bevacizumab pretreated; and 3) Dose Expansion Cohort 3: one to three prior treatments, one of which could have been bevacizumab. A triplet Regimen (Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin) will be opened to evaluate the safety and tolerability and to assess any early signs of activity in participants dosed with the combination regimen. All mirvetuximab soravtansine doses were calculated according to adjusted ideal body weight.

Detailed description:
Participants will continue to receive mirvetuximab soravtansine and/or the combination agent until progressive disease (PD), unacceptable toxicity, or withdrawal of consent, whichever comes first, or until the Sponsor terminates the study.

Arms:
arm 1: Mirvetuximab soravtansine + Bevacizumab administered on Day 1 of each 21-day cycle in Dose Escalation and Dose Expansion phase. arm 2: Mirvetuximab soravtansine + Carboplatin administered on Day 1 of each 21-day cycle in Dose Escalation phase. arm 3: Mirvetuximab soravtansine + Pegylated liposomal doxorubicin administered on Day 1 of each 28-day cycle in Dose Escalation Phase. arm 4: Mirvetuximab soravtansine + Pembrolizumab administered on Day 1 of each 21-day cycle in Dose Escalation and Dose Expansion phase. arm 5: Mirvetuximab soravtansine + Bevacizumab + Carboplatin administered on Day 1 of each 21-day cycle in Dose Expansion phase.

Interventions: intervention 1: Mirvetuximab soravtansine intervention 2: Bevacizumab intervention 3: Carboplatin intervention 4: Pegylated Liposomal Doxorubicin intervention 5: Pembrolizumab
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 1b/2 Study to Evaluate the Safety, Tolerability and 
Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in 
Combination with Bevacizumab, Carboplatin, Pegylated 
Liposomal Doxorubicin, Pembrolizumab, or 
Bevacizumab + Carboplatin, in Adults with Folate Receptor 
Alpha Positive Advanced Epithelial Ovarian Cancer, Primary 
Peritoneal Cancer, or Fallopian Tube Cancer 
Study Number 
IMGN853-0402 
Study Phase: 
1b/2
Product Name: 
Mirvetuximab soravtansine (IMGN853) 
Indication: 
Folate Receptor Alpha Positive Advanced Epithelial Ovarian 
Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer 
Investigators: 
Multicenter 
Sponsor: 
ImmunoGen, Inc. 
830 Winter Street 
Waltham, MA 02451 USA 
Sponsor Contact: 
Phone:
E-mail:
Original Protocol Date: 
11 Aug 2015 
Amendment No. and Date: 
Amendment 1: 23 Sep 2015 
Amendment 1A: 11 Feb 2016 
Amendment 1B: 13 May 2016 
Amendment 2: 21 Jun 2016 
Amendment 3: 26 Jun 2017 
Amendment 4: 14 Nov 2017 
Amendment 5: 21 Sep 2018 
Confidential Statement 
This document is the proprietary and confidential property of ImmunoGen, Inc. 
NCT #NCT02606305


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
2 
SPONSOR SIGNATURE PAGE  
 
 
 
 
 
 
 
 
 
830 Winter Street 
Waltham, MA 02451 
United States of America 
Tel:
 
FAX:
 
 
 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
3 
INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator Brochure for mirvetuximab soravtansine (IMGN853). 
I have read the ImmunoGen Protocol IMGN853-0402 and agree to conduct the study as outlined 
and in conformance with Good Clinical Practice (GCP) and applicable regulatory requirements. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol. 
 
 
 
 
Printed Name, Institution, and Address of Investigator 
 
 
Signature of Investigator 
 
 
Date 
 
 
 
 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
4 
LIST OF ABBREVIATIONS 
Abbreviation or 
Specialist Term 
Explanation 
ADA 
Anti-drug antibody 
ADC 
Antibody drug conjugate 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
AE 
Adverse event 
AESI 
Adverse events of special interest 
AIBW 
Adjusted ideal body weight 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
aPTT 
Activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
Aspartate aminotransferase 
AUC 
Area under the time-concentration curve 
BUN 
Blood urea nitrogen 
CAP 
College of American Pathologists 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
Clearance 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
Maximum plasma concentration 
CNS 
Central nervous system 
CR 
Complete response/remission 
CRC 
Cohort Review Committee 
CRF 
Case report form 
CRO 
Clinical Research Organization  
CT 
Computed Tomography 
CTCAE  
Common Terminology Criteria for Adverse Events 
DLT 
Dose limiting toxicity 
DM4 
N2’-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2’-
deacetylmaytansine 
DM4-Me 
Methylated-N2’-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-
sulfopentyl]-N2’-deacetylmaytansine 
DOR 
Duration of response 
ECG 
Electrocardiogram 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
5 
Abbreviation or 
Specialist Term 
Explanation 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EOC 
Epithelial ovarian cancer 
FDA 
Food and Drug Administration 
FIH 
First in human 
FRα 
Folate receptor α 
GCIG 
Gynecologic Cancer Intergroup  
GCP 
Good clinical practice 
GI 
Gastrointestinal 
HFS 
Hand-foot syndrome 
HGSOC 
High-grade serous ovarian carcinoma 
IBW 
Ideal body weight 
IC50 
50% inhibitory concentration 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization  
IEC 
Independent ethics committee 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IMGN 
ImmunoGen 
IMGN853 
Mirvetuximab soravtansine 
INR 
International normalized ratio 
irAE 
Immune-related adverse event 
IRB 
Institutional review board 
irRECIST 
Immune-related Response Evaluation Criteria in Solid Tumors 
IV 
Intravenous 
LDH 
Lactic acid dehydrogenase 
mAb 
Monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
mRNA 
Messenger ribonucleic acid 
MTD 
Maximum tolerated dose 
MUGA 
Multigated acquisition 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
6 
Abbreviation or 
Specialist Term 
Explanation 
NCI 
National Cancer Institute 
NSCLC 
Non-small cell lung cancer 
ORR 
Objective response rate 
PD 
Progressive disease 
PD-1 
Programmed death receptor-1 
PD-L1 
Programmed cell death ligand 1 
PD-L2 
Programmed cell death ligand 2 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PFT 
Pulmonary function tests 
PgP 
P-glycoprotein 
PK 
Pharmacokinetics 
PO 
Per orem (by mouth) 
PR 
Partial response/remission 
PRES 
Posterior reversible encephalopathy syndrome 
PS 
Performance status 
PT 
Prothrombin time 
PTT 
partial thromboplastin time 
Q2W 
Every 2 weeks 
Q3W 
Every 3 weeks 
RBC 
Red blood cell (count) 
RP2D 
Recommended Phase 2 dose 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse event 
SD 
Stable disease 
SLD 
Sum of the longest diameters 
SUSAR 
Suspected unexpected serious adverse reaction 
t½ 
Half-life 
T1DM 
Type 1 diabetes mellitus 
T3 
Triiodothyronine 
T4 
Thyroxine 
TEAE 
Treatment-emergent adverse event 
tmax 
Time that maximum plasma concentration occurs 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
7 
Abbreviation or 
Specialist Term 
Explanation 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of the normal range 
UPC 
Urine protein creatinine ratio 
US 
United States 
Vss 
Volume of distribution at steady state 
WBC 
White blood cell (count) 
WCBP 
Woman of childbearing potential 
WHO-DD 
World Health Organization – Drug Dictionary 
WNL 
Within normal limits 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
8 
PROTOCOL SYNOPSIS 
Title of Study: A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of 
Mirvetuximab soravtansine (IMGN853) in Combination with Bevacizumab, Carboplatin, Pegylated 
Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab + Carboplatin in Adults with Folate Receptor 
Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube 
Cancer 
Study center(s): approximately 16 in the United States (US), Spain, Belgium, and Canada 
Study period (months): approximately 48 months 
(including treatment and 30-Day Follow-up visit) 
First patient enrolled: December 2015 
Phase of development: 1b/2 
Purpose/rationale: Mirvetuximab soravtansine, also known as IMGN853, is a targeted antibody-drug 
conjugate (ADC) that binds with high affinity to folate receptor alpha (FRα), a glycophosphatidylinositol-
linked protein that shows limited normal tissue expression and high expression in several solid tumors 
(Kelemen 2006), most notably serous epithelial ovarian cancer (EOC) (Miotti 1987, O’Shannessy 
2013). Mirvetuximab soravtansine consists of a humanized anti-FRα monoclonal antibody (mAb) 
attached via a cleavable disulfide containing linker to the cytotoxic maytansinoid DM4. Once released 
within the target cell, DM4 acts as an anti-mitotic agent that inhibits tubulin polymerization and 
microtubule assembly, resulting in cell cycle arrest and apoptosis.  
In vitro studies have demonstrated that mirvetuximab soravtansine binds cell surface FRα with high 
apparent affinity (≤ 0.1 nM) and shows potent (50% inhibitory concentration ≤ 1 nM) and selective 
cytotoxicity against tumor cells expressing FRα. Mirvetuximab soravtansine demonstrates significant 
activity against FRα-positive xenografts, with partial and complete remissions observed in ovarian 
models (Ab 2015). The in vitro and in vivo pharmacologic properties of mirvetuximab soravtansine, 
along with the high expression of FRα in EOC, provided the rationale for exploring mirvetuximab 
soravtansine in a clinical setting. 
In the first-in-human (FIH) Phase 1 study (Study IMGN853-0401) of single-agent mirvetuximab 
soravtansine, objective responses were observed in patients with heavily pretreated FRα-positive EOC 
(≥ 25% of cells with ≥ 2+ staining intensity by immunohistochemistry [IHC]) and endometrial cancer. As 
of February 2018, mirvetuximab soravtansine had a 27% objective response rate (ORR) (95% CI, 
18.5%, 37.1%) and median progression-free survival (PFS) of 4.2 months (95% CI, 3.7, 5.4 months) in 
the 96 patients with platinum-resistant EOC in the patient expansion cohort in Study 0401. The ORR 
was 47% (95% CI, 30.4%, 64.5%) and the median PFS was 6.7 months (95% CI, 4.1, 8.3 months) in 
the subset of 36 patients with FRα-positive (medium/high expression [≥ 50% of cells with ≥ 2+ 
intensity]) platinum-resistant EOC with one to three prior regimens treated as part of a 96-patient 
expansion cohort in Study 0401 (clinical study report Table 16). Similarly, results of a pooled analysis of 
113 patients showed an ORR of 30% (95% CI, 21.8%, 39.4%), a median PFS of 4.3 months (95% CI, 
3.9, 5.4), and a duration of response of 19.3 weeks (95% CI, 18, 34 weeks). Treatment-related adverse 
events (AEs) occurring in > 20% of patients in this cohort included diarrhea, blurred vision, fatigue, 
nausea, and increased aspartate aminotransferase (AST), and were mostly low grade. Blurred vision 
was likely related to the development of corneal keratopathy, transient microcysts that form in the 
corneal epithelium, causing temporary symptoms.  
Bevacizumab, carboplatin, and pegylated liposomal doxorubicin are currently in use for the treatment of 
EOC. Doublet combinations of mirvetuximab soravtansine with bevacizumab, carboplatin, and 
pegylated liposomal doxorubicin have all demonstrated additive activity in nonclinical models.  
Pembrolizumab, an anti-programmed death receptor-1 (PD-1) mAb, is approved for the treatment of 
melanoma, non–small-cell lung cancer, head and neck squamous cell cancer, classical Hodgkin 
lymphoma, urothelial carcinoma, microsatellite instability high solid tumors, and 
gastric/gastroesophageal junction adenocarcinoma and has shown preliminary anti-tumor activity as a 
single agent in EOC (Varga 2015). 
The mirvetuximab soravtansine + bevacizumab and mirvetuximab soravtansine + carboplatin dose 
escalation cohorts in this study have been completed, with dose levels explored to the highest 
allowable per this protocol. The safety and tolerability data show that each of the doublets was 
generally well tolerated; no new safety signals were observed at the highest dose levels explored. The 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
9 
safety profile is consistent with the reference safety profile information for each drug and in line with 
expectations for a population of previously treated ovarian cancer patients. 
Furthermore, initial signs of anti-tumor activity were seen both doublet combinations explored in this 
study. The ORR and the median PFS observed in the mirvetuximab soravtansine + bevacizumab 
combination across all dose levels and FRα expression levels (n = 14) were 29% (95% CI, 8, 58) and 
9.5 months (95% CI, 3.5, 15.2), respectively (O’Malley 2017). The observed anti-tumor activity in a 
heavily pre-treated (median of 6 prior lines of therapy [range, 2-8]), platinum-resistant population 
compares favorably with what has been demonstrated in less heavily pre-treated, platinum-resistant 
ovarian cancer patients following treatment with bevacizumab + standard chemotherapy (Pujade-
Lauraine 2014). The ORR and median PFS observed in the mirvetuximab soravtansine + carboplatin 
combination across all dose levels and FRα expression levels (n = 17) were 65% (95% CI, 38, 86) and 
12.1 months (95% CI, 9.0, 15.0) (O’Malley 2017). The observed anti-tumor activity in a pre-treated 
(median 3 prior regimens [range 1-5]), platinum-sensitive (72% with a PFS 6-12 months) population 
compared favorably with what has been demonstrated in standard platinum-based doublets in a 
recurrent platinum-sensitive setting (Aghajanian 2012, Coleman 2017, and Gladieff 2012). 
Bevacizumab, in combination with carboplatin-based doublets, has been approved for frontline 
treatment of patients with EOC in the European Union since 2011; more recently (December 2016) the 
use of bevacizumab + carboplatin–based doublet regimens have been approved in the US for the 
treatment of patients with recurrent, platinum-sensitive EOC. These approvals have supported an 
increased and broader use of triplet therapy for platinum-sensitive EOC. Therefore, given the 
preliminary safety and initial anti-tumor activity of mirvetuximab soravtansine both with bevacizumab 
and with carboplatin, and the increased use of bevacizumab and carboplatin in triplet therapy, this 
study will explore the safety and anti-tumor activity of the triplet therapy mirvetuximab soravtansine + 
bevacizumab + carboplatin in patients with recurrent platinum-sensitive EOC. Because of the 
successful full dose experiences with each of the combination partners as doublets with mirvetuximab 
soravtansine, the triplet therapy will initially explore a combination using full doses of all 3 agents. The 
dose will be explored in a stepwise manner, with a pause to review safety data after the first six and 
then 12 patients have completed their first cycle of treatment. 
The study is designed to establish the maximum tolerated dose (MTD) and determine the 
recommended Phase 2 dose (RP2D) of mirvetuximab soravtansine when administered in combination 
with either bevacizumab, carboplatin, pegylated liposomal doxorubicin, or pembrolizumab. The study 
will also investigate activity signals and safety and tolerability of a triplet dose regimen of mirvetuximab 
soravtansine + bevacizumab + carboplatin. All study treatments will be administered intravenously (IV) 
to adult patients with FRα-positive ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. 
The safety, tolerability, immunogenicity of mirvetuximab soravtansine, and preliminary anti-tumor 
activity of mirvetuximab soravtansine in combination with bevacizumab, carboplatin, pegylated 
liposomal doxorubicin, pembrolizumab, or bevacizumab + carboplatin will be characterized. The 
pharmacokinetics (PK) and immunogenicity of mirvetuximab soravtansine will be characterized along 
with bevacizumab, carboplatin, and pegylated liposomal doxorubicin concentrations. Pembrolizumab 
concentrations may be evaluated, if warranted, because of a safety signal.  
Primary Objectives  
Dose Escalation (Regimens A Through D) 
• 
Evaluate the safety and tolerability of mirvetuximab soravtansine when given in 
combination with bevacizumab, carboplatin, or pegylated liposomal doxorubicin, or 
pembrolizumab (Regimens A, B, C and D, respectively) in patients with EOC, primary 
peritoneal cancer, or fallopian tube cancer 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) 
• 
Assess preliminary response-based anti-tumor activity of mirvetuximab soravtansine when 
administered in combination with bevacizumab (Regimen A) or pembrolizumab 
(Regimen D) and in combination with bevacizumab and carboplatin (Regimen E) in 
patients with EOC, primary peritoneal cancer, or fallopian tube cancer 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
10 
Primary Endpoints 
Dose Escalation (Regimens A Through D) 
• 
Treatment-emergent AEs, laboratory test results, physical examination, electrocardiograms 
(ECGs), and vital signs  
Dose Expansion (Regimens A and D) and Regimen E (Triplet) 
• 
Objective response rate, defined as percentage of patients with confirmed response 
(complete response/remission [CR] + partial response/remission [PR]) as assessed by 
Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1  
Secondary Objectives 
• 
Evaluate the safety and tolerability of mirvetuximab soravtansine when administered in 
combination with bevacizumab or pembrolizumab (Dose Expansion, Regimens A and D, 
respectively) and in combination with bevacizumab and carboplatin (Regimen E [Triplet]) in 
patients with EOC, primary peritoneal cancer, or fallopian tube cancer 
• 
Assess preliminary response-based anti-tumor activity of the combination Regimens (Dose 
Escalation, Regimens A through D) 
• 
Assess PFS 
• 
Measure duration of response (DOR): the time from first objective response (CR/PR) to the 
time of progressive disease (PD) among those who have achieved a PR or CR  
• 
Assess Gynecologic Cancer Intergroup (GCIG) CA125 response rate of the combination 
Regimens 
• 
Characterize PK of mirvetuximab soravtansine when used in combination Regimens 
• 
Evaluate bevacizumab, carboplatin, and pegylated liposomal doxorubicin concentrations 
when administered in combination with mirvetuximab soravtansine  
• 
Characterize immunogenicity of mirvetuximab soravtansine  
Secondary Endpoints 
• 
Treatment-emergent AEs, changes in laboratory test results, physical examination, ECGs, 
and vital signs (Dose Expansion [Regimens A and D] and Regimen E [Triplet]). 
• 
Objective response rate, defined as percentage of patients with confirmed response (CR + 
PR) as assessed by RECIST Version 1.1 (Dose Escalation, Regimens A through D)  
• 
Progression-free survival, defined as time from first dose to PD or death, whichever occurs 
first 
• 
Duration of response, defined as the time from first objective response (CR/PR) to the time 
of PD among those who have achieved a PR or CR  
• 
Number of patients with GCIG CA125 criteria clinical responses  
• 
Mirvetuximab soravtansine PK parameters for intact ADC, total antibody, DM4, and S-
methyl DM4 include, but are not limited to, Cycle 1 and Cycle 3 maximum plasma 
concentration (Cmax), area under the time-concentration curve (AUC), terminal half-life (t½), 
clearance (CL), volume of distribution at steady state (Vss), and time that Cmax occurs (tmax) 
• 
Concentration data of bevacizumab, carboplatin, and pegylated liposomal doxorubicin will 
be measured before and after bevacizumab, carboplatin, and pegylated liposomal 
doxorubicin infusions (Cycle 1 through Cycle 6) 
• 
Immunogenicity: presence of anti-drug antibodies to mirvetuximab soravtansine   
Exploratory Objectives  
• 
Assess any association between FRα expression levels and clinical response 
• 
Identify or evaluate potential biomarkers in blood and tumor tissue that might predict 
response to each of the four combinations  
• 
Evaluate pembrolizumab concentrations if warranted by a safety signal (Regimen D only) 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
11 
• 
Assess anti-tumor activity of the combination with pembrolizumab per immune-related 
RECIST (irRECIST) (Regimen D only) 
Exploratory Endpoints  
• 
Correlation of FRα expression, by IHC (protein), quantitative reverse transcriptase-
polymerase chain reaction (mRNA), or other quantitative methods, to clinical endpoints 
• 
Measure biomarkers in blood and tumor tissue including, but not limited to, mutational and 
genomic alterations of tumor samples; expression and activation of oncogenic genes and 
pathways in tumor samples; expression and polymorphism of drug transporters such as 
multidrug-resistance protein-1 (p-glycoprotein); the genotype of FcγR; expression and of 
immune-related genes and gene signatures (Regimen D only), and infiltration of tumor-
related immune cells (Regimen D only) 
• 
Concentration data for pembrolizumab if warranted by a safety signal (Regimen D only)  
• 
Evaluate efficacy endpoints per irRECIST (Regimen D only)  
– Progression-free survival, ORR, and DOR per irRECIST are defined as specified for the 
respective endpoints using RECIST Version 1.1 above, except that a confirmation 
assessment of PD (at least 4 weeks after the initial PD assessment) is required for 
subjects who remain on treatment after documented PD per RECIST Version 1.1. 
Subjects who discontinue treatment after documented PD assessment per RECIST 
Version 1.1 will be counted as having PD on the date of the documented PD 
assessment.  
Note: Unless specifically warranted by relevance to safety or efficacy endpoints, the exploratory 
endpoints will not be reported in the clinical study report. 
Number of patients (planned): It is estimated that approximately 311 to 355 patients will be enrolled 
into the study. 
Dose Escalation Phase:  
• 
Regimen A (mirvetuximab soravtansine + bevacizumab): approximately 16 patients; 
additional patients will be recruited to ensure that 10 patients are treated at the MTD 
• 
Regimen B (mirvetuximab soravtansine + carboplatin): approximately 22 patients; 
additional patients will be recruited to ensure that 10 patients are treated at the MTD 
• 
Regimen C (mirvetuximab soravtansine + pegylated liposomal doxorubicin): 
approximately 22 patients; additional patients, up to 10 patients, will be recruited and treated at 
the MTD 
• 
Regimen D (mirvetuximab soravtansine + pembrolizumab): approximately 16 patients; 
additional patients will be recruited to ensure that 10 patients are treated at the MTD 
Dose Expansion Phase:  
Regimen A: mirvetuximab soravtansine + bevacizumab 
Patients enrolled in this phase may be assigned to one of three Dose Expansion Cohorts according to 
previous exposure to bevacizumab as follows:  
1. Dose Expansion Cohort 1: bevacizumab naïve; will enroll approximately 20 patients  
2. Dose Expansion Cohort 2: bevacizumab pretreated; may enroll approximately 35 patients 
3. Dose Expansion Cohort 3: patients with at least one but no more than three prior systemic 
treatment regimens, where prior regimens may have included bevacizumab; may enroll 
approximately 60 patients 
Regimen D: mirvetuximab soravtansine +pembrolizumab 
The Dose Expansion phase will enroll sufficient patients to ensure that 35 patients are FRα ≥ 50% of 
tumor staining at ≥ 2 + intensity 
Regimen E (Triplet): mirvetuximab soravtansine + bevacizumab + carboplatin 
This cohort will enroll approximately 50 patients to ensure that 40 patients will be treated at the MTD. 
The estimated study duration is approximately 48 months for patient accrual, dosing, treatment and 
follow-up. 
Study Design Overview and Schema: This is an open label, Phase 1/2b, non-randomized 
combination study of mirvetuximab soravtansine with bevacizumab, carboplatin, pegylated liposomal 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
12 
doxorubicin, pembrolizumab, or bevacizumab + carboplatin in adult patients with FRα-positive 
advanced EOC, primary peritoneal cancer, or fallopian tube cancer.  
The treatment regimens and planned dose levels for the dose escalation phase of the study are 
outlined below and in Table 1, Table 2, Table 3, and Table 4.  
Intermediate or lower dose levels of pegylated liposomal doxorubicin, bevacizumab, or carboplatin may 
be explored if dose-limiting toxicities (DLTs) can be attributed to their mechanism of action. Higher 
doses of pegylated liposomal doxorubicin (up to 50 mg/m2) and carboplatin (AUC6) also may be 
considered. The maximum allowable doses of each study drug are as follows: mirvetuximab 
soravtansine 6.0 mg/kg adjusted ideal body weight (AIBW) every 3 weeks (Q3W), mirvetuximab 
soravtansine 6.0 mg/kg every 4 weeks (Q4W), bevacizumab 15 mg/kg Q3W, carboplatin AUC6 Q3W, 
pegylated liposomal doxorubicin 50 mg/m2 Q4W, and pembrolizumab 200 mg Q3W. 
If a patient is eligible for more than one Regimen, the investigator will assign the patient to a Regimen 
on the basis of the patient’s medical history, prior treatment, and/or patient preference.  
Regimen A: mirvetuximab soravtansine + bevacizumab administered on Day 1 of each 21-day cycle  
Regimen B: mirvetuximab soravtansine + carboplatin administered on Day 1 of each 21-day cycle 
Regimen C: mirvetuximab soravtansine + pegylated liposomal doxorubicin administered on Day 1 of 
each 28-day cycle 
Regimen D: mirvetuximab soravtansine + pembrolizumab administered on Day 1 of each 21-day 
cycle 
A triplet cohort will be opened because enrollment and safety from Regimens A and B have been 
established, and Regimen A (Dose Expansion Cohorts) enrollment is currently ongoing. The planned 
doses for patients receiving the triplet dose (Regimen E) are derived from all available data in 
Regimens A and B and shown in Table 5 below. 
Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin administered on Day 1 of each 
21-day cycle 
Table 1: Planned Dose Levels (Dose Escalation) for Regimen A 
Dose Level 
Regimen A 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Bevacizumabc 
(mg/kg, D1q3W) 
-1 
4 
15 
1 
5 
15 
2 
6 
15 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of bevacizumab is 15 mg/kg. 
Table 2: Planned Dose Levels (Dose Escalation) for Regimen B 
Dose Level 
Regimen B 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Carboplatinc 
(AUC, D1q3W) 
-1 
4 
AUC4 
1 
5 
AUC4 
2 
5 
AUC5 
3 
6 
AUC5 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of carboplatin is AUC6, subject to Cohort Review Committee review. 
 
 
 
 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
13 
 
Table 3: Planned Dose Levels (Dose Escalation) for Regimen C 
Dose Level 
Regimen C 
Mirvetuximab Soravtansinea 
(mg/kg, D1q4W)b  
Pegylated Liposomal Doxorubicinc 
(mg/m2, D1q4W) 
-1 
4 
30 
1 
5 
30 
2 
5 
40 
3 
6 
40 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 4 weeks. 
c The approved dose of pegylated liposomal doxorubicin for ovarian cancer is 50 mg/m2; however, a decrease 
in the incidence of hand-foot syndrome was observed at a dose of 40 mg/m2 without significant loss in 
efficacy. Maximum allowable dose is 50 mg/m2, subject to Cohort Review Committee review. 
Table 4: Planned Dose Levels (Dose Escalation) for Regimen D 
Dose Level 
Regimen D 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Pembrolizumabc 
(mg, D1q3W) 
-1 
4 
200 
1 
5 
200  
2 
6 
200 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of pembrolizumab is 200 mg. 
Table 5: Planned Dose Levels (Triplet Cohort) for Regimen E 
Dose Level 
Regimen E 
Mirvetuximab 
Soravtansinea 
(mg/kg, D1q3W)b 
Bevacizumab 
(mg/kg, D1q3W) 
Carboplatinc 
(AUC, D1q3W) 
-2 
5 
15 
AUC 4 
-1d 
6 
15 
AUC 4 
-1e 
5 
15 
AUC 5 
1 
6 
15 
AUC 5 
a Mirvetuximab soravtansine dose calculated using AIBW. 
b Day 1, every 3 weeks. 
c Carboplatin dose may be reduced to AUC4 if safety data from the first six or 12 patients suggest that the 
triplet dose is not being tolerated. 
d Dose reduction of carboplatin due to carboplatin-associated toxicity. 
e Dose reduction of mirvetuximab soravtansine due to mirvetuximab soravtansine–associated toxicity. 
The starting dose of mirvetuximab soravtansine will be 5 mg/kg, with the dose calculated using AIBW, 
which is one dose level lower than the RP2D (6 mg/kg using AIBW) defined in the FIH Study IMGN853-
0401. All mirvetuximab soravtansine doses will be calculated according to AIBW. Regimens A 
through D, inclusive, will be evaluated in parallel and independently.  
This Phase 1b study comprises a Dose Escalation phase followed by an MTD Expansion phase to 
further characterize the safety profile and confirm the MTD as the RP2D. A triplet Regimen 
(Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin) will be opened to evaluate the 
safety and tolerability and to assess any early signs of activity in patients dosed with the combination 
Regimen.  
The Dose Escalation phase will follow a standard 3 + 3 cohort design. No intra-patient dose-escalation 
will be allowed. The MTD will be determined from the assessment of DLTs during the first treatment 
cycle (Table 6). The primary aim of the Dose Escalation phase is to evaluate the safety and tolerability 
of the four dosing Regimens, and to identify the MTD and characterize the PK of mirvetuximab 
soravtansine, bevacizumab, carboplatin, and pegylated liposomal doxorubicin. The PK profile of 
pembrolizumab may be characterized if warranted because of a safety signal. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
14 
Table 6: DLT Definitions 
Toxicity 
DLT Definition Criteriaa 
Dose delays 
Failure to meet re-treatment criteria within the specified time frame 
Hematology 
• 
CTCAE Grade 4 neutropenia ≥ 7 days 
• 
CTCAE ≥ Grade 3 febrile neutropenia, defined as ANC < 1,000/mm3 with 
a single temperature reading of > 38.3°C or sustained temperature of 
≥ 38°C for > 1 hour 
• 
CTCAE Grade 3 thrombocytopenia, associated with clinically significant 
bleeding that requires transfusion therapy 
• 
CTCAE Grade 4 thrombocytopenia  
Non-hematologic and 
other DLTs 
• 
CTCAE ≥ Grade 3 nausea or vomiting despite the use of optimal 
anti-emetic treatments 
• 
CTCAE ≥ Grade 3 diarrhea despite the use of optimal anti-
diarrheal treatments 
• 
CTCAE Grade 2 diarrhea lasting > 14 days (Regimen D only) 
• 
CTCAE ≥ Grade 3 ocular AEs 
• 
CTCAE ≥ Grade 3 pneumonitis 
• 
Other non-hematologic toxicities of CTCAE ≥ Grade 3 except for 
the following: 
– AEs related to underlying disease. 
– CTCAE Grade 3 fatigue. 
– Isolated, asymptomatic Grade 3 abnormalities in biochemistry 
laboratory values that last for ≤ 7 days. This includes electrolyte 
abnormalities that respond to medical intervention. 
a An AE meeting criteria is considered a DLT if the event occurred during the first cycle. 
For any dose-limiting hepatic toxicity, evaluations should be performed to determine the underlying etiology and 
rule out drug-induced liver injury (Hy’s Law).  
ANC = absolute neutrophil count, CTCAE = Common Terminology Criteria for Adverse Events. 
To better characterize safety, 10 patients may receive mirvetuximab soravtansine and the assigned 
combination agent at the MTD established for Regimens A, B, C, and D.  
The Dose Expansion phase of the trial, which is planned for mirvetuximab soravtansine in combination 
with bevacizumab (Regimen A) and for mirvetuximab soravtansine in combination with pembrolizumab 
(Regimen D), will open after the Cohort Review Committee (CRC) reviews safety data from Dose 
Escalation and agrees the dose is safe to proceed to Expansion. Dose Expansion will commence 
enrollment pending Sponsor decision. In addition, the CRC will assess safety of the triplet after six and 
then 12 patients have completed Cycle 1 at each dose levels evaluated. 
 
Regimen A (mirvetuximab soravtansine + bevacizumab) 
Patients in the dose expansion phase may be assigned according to prior exposure to bevacizumab 
and disease diagnosis into three dose expansion cohorts as follows:  
1. Dose Expansion Cohort 1: bevacizumab naïve; will enroll approximately 20 patients  
2. Dose Expansion Cohort 2: bevacizumab pretreated; may enroll 35 patients  
3. Dose Expansion Cohort 3: with one to three prior systemic therapies, and one prior therapy 
could have been bevacizumab; may enroll 60 patients 
Regimen D (mirvetuximab soravtansine + pembrolizumab): 
The Dose Expansion phase will enroll sufficient patients such that 35 patients are FRα ≥ 50% of tumor 
staining at ≥ 2+ intensity in the Dose Expansion phase. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
15 
The aims of the Dose Expansion phase are to further evaluate the safety, tolerability, and anti-tumor 
activity of mirvetuximab soravtansine in combination with bevacizumab or pembrolizumab.  
The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03 will be used to grade AEs. 
Regimen E (triplet dose: mirvetuximab soravtansine + bevacizumab + carboplatin) 
This cohort may enroll up to approximately 50 patients, as exploration of alterative doses is required to 
enroll approximately 40 planned patients to be dosed at the maximum dose level determined to be 
safe.  
The aims of this cohort are to evaluate safety and tolerability of the combination and to assess for early 
signs of activity. The starting doses used in this cohort will be derived from all evaluable data from 
Regimens A and B. The MTD will be determined from the assessment of DLTs during the first 
treatment cycle (Table 6). 
Initially, six patients will be dosed at the target triplet dose (Table 5). If there are < 2 Cycle 1 DLTs 
(total), another six patients will be dosed. If there are < 4 Cycle 1 DLTs (total) in all 12 patients, the 
remaining 28 patients will be enrolled for a total of approximately 40 planned patients. 
If either ≥ 2 DLTs or ≥ 4 DLTs are observed in the first six or 12 patients, respectively, either the 
mirvetuximab soravtansine dose or the carboplatin dose will be reduced. The reduced triplet doses will 
always be explored in the same step-wise manner as detailed above. A total of 12 patients (6 + 6 
patients) will be assessed at a dose before the remaining 28 patients being enrolled. The decision of 
whether to reduce the mirvetuximab soravtansine dose or the carboplatin dose will be made according 
to the DLTs observed, and the new dose levels will be explored as follows: 
a. For DLTs that cannot solely be attributable to mirvetuximab soravtansine, the carboplatin dose 
will be reduced. 
b. For DLTs that are solely attributable to mirvetuximab soravtansine, the mirvetuximab 
soravtansine dose will be reduced. 
If after the doses of carboplatin (a) or mirvetuximab soravtansine (b) are reduced, ≥ 2 DLTs or 
≥ 4 DLTs are observed in the first six or 12 patients, respectively, the dose of the other agent 
(mirvetuximab soravtansine [for a] or carboplatin [for b]) will also be reduced. The triplet dose with the 
reduced mirvetuximab soravtansine and carboplatin doses will then be evaluated. 
 
 
 
 
 
 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
16 
Study Design Schema 
a Enrolled 46 patients to ensure 35 patients with tumors expressing FRα at ≥ 50% of tumor staining at intensity 
≥ 2+ and 11 patients with a FRα 25%-49% of tumor staining at intensity ≥ 2+. 
b Enroll approximately 50 patients to evaluate 40 patients at the MTD. 
Study Eligibility Criteria:  
Inclusion Criteria  
Inclusion Criteria for All Patients (Dose Escalation and Dose Expansion, Regimen-Specific) 
1. Pathologically documented advanced EOC (including primary peritoneal cancer and fallopian 
tube cancer). 
2. Female and ≥ 18 years of age at the time of the first screening visit. 
3. Eastern Cooperative Oncology Group performance status 0 or 1. 
4. Measurable disease: 
a. 
Dose Escalation: Patients may have measurable or non-measurable disease.  
b. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet): Patients must have at least 
one lesion that meets the definition of measurable disease according to RECIST 
Version 1.1. 
5. Willing to provide an archival tumor tissue block or slides, or a new biopsy if archival tumor 
tissue is unavailable. 
a. 
Regimen D only: Patients must be willing to undergo two tumor biopsy collections using a 
non-significant risk procedure (see Section 2.1.1). The first biopsy will be taken before the 
first dose of study treatment and the second, taken on Cycle 2 Day 8 (± 3 days).  
6. Confirmation of FRα positivity by IHC. If the archival tumor tissue does not meet FRα criteria, a 
new tumor biopsy may be submitted and used to meet this criterion. FRα expression levels 
must meet the following criteria: 
a. 
Dose Escalation (Regimens A through D): ≥ 25% of tumor staining at ≥ 2+ intensity 
b. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet): ≥ 50% of tumor staining at 
≥ 2+ intensity 
7. Time from prior therapy: 
a. 
Systemic anti-neoplastic therapy: five half-lives or 4 weeks, whichever is shorter. 
Hormonal therapy is not considered anti-neoplastic therapy. 
b. 
Radiotherapy: wide-field radiotherapy (eg, > 30% of marrow-bearing bones) completed at 
least 4 weeks, or focal radiation completed at least 2 weeks, before starting study 
treatment. 
8. Recovered or stabilized to NCI CTCAE ≤ Grade 2 from all therapy-related toxicities (Regimens 
A through C and Regimen E). 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
17 
9. Resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except 
alopecia). If patient received major surgery or radiation therapy of > 30 Gy, they must have 
recovered from the toxicity and/or complications from the intervention (Regimen D only). 
10. Platinum sensitivity: 
a. 
Dose Escalation and Dose Expansion: Regimens A (Cohorts 1 and 2) and D and Dose 
Escalation Regimen C: Patients must have disease that is resistant to platinum therapy. 
Platinum-resistant disease is defined as disease that responded to primary platinum 
therapy and then progressed within 6 months (182 days) after the date of the last dose of 
platinum therapy, or disease that progressed during or within 6 months (182 days) after 
the date of the last dose of the subsequent platinum therapy. 
b. 
Dose Escalation, Regimen B: Patients must have platinum-sensitive disease. Platinum-
sensitive disease is disease that responded to the last platinum therapy received before 
study entry and did not progress within 6 months (182 days) after the date of the last dose 
of platinum therapy. 
c. 
Regimen E (Triplet): Patients must have platinum-sensitive disease. Platinum-sensitive 
disease is disease that responded to the last platinum therapy received before study entry 
and did not progress within 6 months (182 days) after the date of the last dose of platinum 
therapy. The requirements to demonstrate platinum sensitivity (responsiveness and time 
to progression) apply to each of the patient’s prior platinum-containing regimens.  
d. 
Dose Expansion: Regimen A, Cohort 3: Patients may have either platinum-resistant 
disease or platinum-sensitive disease, where a non-platinum doublet is an appropriate 
next line of therapy. 
11. Number of prior therapies (where adjuvant ± neoadjuvant will be considered one regimen and 
maintenance therapy will be considered to be part of the preceding regimen; hormonal therapy 
counts as a separate line of therapy unless given as maintenance): 
a. 
Dose Escalation (Regimens A through D): There is no upper limit to the number of prior 
treatment regimens received. 
b. 
Dose Expansion Regimen A, Cohort 1: Patients must have received ≤ two prior systemic 
treatment regimens. 
c. 
Dose Expansion Regimen A, Cohort 2: Patients must have received at least one but not 
more than five prior systemic treatment regimens. At least one of the prior systemic 
treatment regimens must have included bevacizumab. 
d. 
Dose Expansion Regimen A, Cohort 3: Patients must have received at least one but no 
more than three prior systemic treatment regimens, where prior regimens may have 
included bevacizumab. 
e. 
Dose Expansion Regimen D: Patients must have received at least two but not more than 
four prior systemic treatment regimens. 
f. 
Regimen E (Triplet): Patients must have received at least one but not more than two prior 
systemic treatment regimens; prior systemic treatment regimens may have included 
vascular endothelial growth factor inhibitors (including bevacizumab) and must have 
included at least one platinum-based chemotherapy. 
12. Prior folate receptor–targeting investigational agents treatment: 
a. 
Dose Escalation (Regimens A through C): Prior treatment with folate receptor–targeting 
investigational agents, including mirvetuximab soravtansine (provided it was not 
discontinued because of AEs), is allowed.  
b. 
Dose Escalation (Regimen D), Dose Expansion (Regimens A and D), and Regimen E 
(Triplet): Patients who have received prior mirvetuximab soravtansine are excluded.  
13. Major surgery (not including placement of vascular access device or tumor punch/scrape 
biopsies) must be completed 4 weeks before Day 1. Patients must have recovered or stabilized 
from the side effects before study treatment. 
14. Adequate hematologic, kidney, and liver function as defined by the following parameters: 
a. 
Absolute neutrophil count ≥ 1.5 × 109/L (1,500/μL). 
b. 
Platelet count ≥ 100 × 109/L (100,000/μL); must not be transfused within previous 10 days. 
c. 
Hemoglobin ≥ 9.0 g/dL. 
d. 
Serum creatinine ≤ 1.5 times the upper limit of the normal range (ULN) or 24-hour 
creatinine clearance of ≥ 60 mL/minute. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
18 
e. 
AST ≤ 2.5 times the ULN; alanine aminotransferase ≤ 2.5 times the ULN. 
f. 
Serum bilirubin ≤ 1.5 times the ULN (patients with documented diagnosis of Gilbert 
syndrome are eligible if total bilirubin is < 3.0 times the ULN). 
g. 
International normalized ratio or prothrombin time (PT) ≤ 1.5 times the ULN unless patient 
is receiving anticoagulant therapy, as long as PT or partial thromboplastin time (PTT) is 
within therapeutic range of intended use of anticoagulants. 
h. 
Activated partial thromboplastin time ≤ 1.5 times the ULN unless patient is receiving 
anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of 
anticoagulants. 
i. 
Dose Escalation and Dose Expansion (Regimen D): thyroid-stimulating hormone within 
normal limits (WNL). If TSH is not WNL, the patient is eligible if total triiodothyronine (T3) 
or free T3 and free thyroxine (T4) are WNL.  
15. Willing and able to sign the informed consent form and to adhere to the study visit schedule 
and other protocol requirements. 
16. Woman of childbearing potential (WCBP), defined as a sexually mature woman who has not 
undergone surgical sterilization or who has not been naturally postmenopausal for at least 
12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive 
months) must agree to use effective contraceptive methods. Acceptable single methods 
include intrauterine device, vasectomy of a female patient’s male partner, and contraceptive 
rod implanted into the skin. Abstinence (relative to heterosexual activity) can be used as the 
sole method of contraception if it is consistently employed as the patient’s preferred and usual 
lifestyle and if considered acceptable by local regulatory agencies and independent ethics 
committees/institutional review boards. Periodic abstinence (eg, calendar, ovulation, sympto-
thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 
Acceptable combination methods (requiring use of two of the following) are acceptable: 
diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide); 
cervical cap with spermicide (nulliparous women only); contraceptive sponge (nulliparous 
women only); male condom or female condom (cannot be used together); hormonal 
contraceptive such as oral contraceptive pill, estrogen/progestin pill, or progestin-only pill; 
contraceptive skin patch; vaginal contraceptive ring; or subcutaneous contraceptive injection. 
Acceptable methods of contraception must be used while on study treatment and for at least 
12 weeks after the last dose of mirvetuximab soravtansine, for at least 6 months after the last 
dose of bevacizumab, carboplatin, or pegylated liposomal doxorubicin, and for at least 
4 months after the last dose of pembrolizumab. 
17. WCBP must have a negative pregnancy test within 3 days before the first dose of study 
treatment. 
Exclusion Criteria  
1. Male patients. 
2. Primary platinum-refractory disease. Platinum refractory is defined as disease that has not 
responded to a primary platinum-based regimen or progressed within 30 days after primary 
platinum-based therapy. 
3. Clear-cell, mucinous histology, mixed histology with mucinous component, sarcoma, 
sarcomatous component, or low-grade ovarian cancer. 
4. Active or chronic corneal disorders, including but not limited to the following: Sjogren 
syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, 
active herpetic keratitis, monocular vision, and/or other active ocular conditions requiring 
ongoing treatment/monitoring, such as wet age-related macular degeneration requiring 
intravitreal injections, active diabetic retinopathy with macular edema, and/or presence of 
papilledema. 
5. > Grade 1 peripheral neuropathy.  
6. Serious concurrent illness or clinically relevant active infection (testing not required), including 
but not limited to the following: 
a. Known active hepatitis B or C  
b. Known HIV infection 
c. 
Varicella-zoster virus (shingles)  
d. Cytomegalovirus infection  


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
19 
e. Any other known concurrent infectious disease requiring IV antibiotics within 2 weeks 
before study enrollment 
7. Clinically significant cardiac disease including any one of the following: 
a. Recent myocardial infarction (≤ 6 months before Day 1) 
b. Unstable angina pectoris 
c. 
Uncontrolled congestive heart failure (New York Heart Association > Class II)  
d. Uncontrolled hypertension (≥ CTCAE Version 4.03 Grade 3) 
e. History of hypertensive crisis or hypertensive encephalopathy 
f. 
Uncontrolled cardiac arrhythmias 
g. Clinically significant vascular disease (eg, aortic aneurysm or dissecting aneurysm) 
h. Severe aortic stenosis 
i. 
Clinically significant peripheral vascular disease 
j. 
≥ Grade 3 cardiac toxicity following prior chemotherapy 
k. 
Heart rate–corrected QT interval > 470 msec on the screening ECG 
8. History of multiple sclerosis or other demyelinating disease and/or Eaton-Lambert syndrome 
(para-neoplastic syndrome).  
9. History of hemorrhagic or ischemic stroke within the last 6 months.  
10. History of cirrhotic liver disease. 
11. History of non-infectious interstitial lung disease, including non-infectious pneumonitis that 
required steroids or current pneumonitis.  
12. Prior hypersensitivity to monoclonal antibodies and/or severe hypersensitivity (≥ Grade 3) to 
pembrolizumab and/or any of its excipients. 
13. Women who are pregnant or lactating or expecting to conceive children within the projected 
duration of the trial, starting with the screening visit through 6 months after the last dose of 
study treatment (Regimens A, B, and C only). 
14. Carcinomatous meningitis, untreated central nervous system (CNS) disease, or symptomatic 
CNS metastasis. Patients with previously treated CNS metastasis (excluding carcinomatous 
meningitis) may participate if their disease is stable (without evidence of progression by 
imaging, using identical imaging modality at each assessment, for at least 4 weeks before the 
first dose of study treatment), have no evidence of new or emerging CNS metastasis, and are 
not using steroids for at least 7 days before the first dose of study treatment. 
15. History or evidence of thrombotic or hemorrhagic disorders within 6 months before the first 
dose of study treatment. 
16. Required used of folate-containing supplements (eg, folate deficiency). 
17. Known additional malignancy that is progressing or required active treatment within 3 years 
before the first dose of study treatment, excluding adjuvant hormonal therapy for breast cancer 
that was completed. Other exceptions include basal cell carcinoma of the skin, squamous cell 
carcinoma of the skin that has undergone potentially curative therapy, and other in situ 
cancers.  
Additional Exclusion Criteria for Regimen A and Regimen E 
18. History of bowel obstruction (including sub-occlusive disease) related to underlying disease 
within 6 months before the start of study treatment. 
19. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess, or 
evidence of rectosigmoid involvement by pelvic examination, bowel involvement on computed 
tomography scan, or clinical symptoms of bowel obstruction.  
20. Prior radiotherapy to the pelvis or abdomen (Dose Escalation phase only). 
21. Surgery (including open biopsy) within 4 weeks before starting study therapy (within 24 hours 
for minor surgical procedures) or anticipated need for major surgery during study treatment. 
22. Non-healing wound, ulcer, or bone fracture.  
23. Hemoptysis ≥ 0.5 teaspoon of red blood within 4 weeks before first study treatment. 
24. History of posterior reversible encephalopathy syndrome. 
25. Clinically significant proteinuria: urine-protein (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; 
patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine collection and 
must show result ≤ 1 gram of protein in 24-hour period. 
26. History of pulmonary embolization. 
27. History of Grade 4 thromboembolic events. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
20 
Additional Exclusion Criteria for Regimen C 
28. Prior treatment with pegylated liposomal doxorubicin and/or doxorubicin. 
29. Left ventricular ejection fraction defined by multigated acquisition scan/echocardiogram that is 
below the institutional lower limit of normal. 
Additional Exclusion Criteria for Regimen D 
30. Received a live vaccine within 30 days before study enrollment. Seasonal flu vaccines that do 
not contain live virus are permitted. 
31. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of 
immunosuppressive therapy within 7 days before the first dose of study treatment. The use of 
physiologic doses of corticosteroids may be approved after consultation with the Sponsor. 
32. Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with 
use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement 
therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or 
pituitary insufficiency) is not considered a form of systemic treatment. 
33. Prior anti-cancer mAb within 4 weeks before study Day 1 or has not recovered (ie, ≤ Grade 1 at 
baseline) from AEs due to agents administered more than 4 weeks earlier. 
34. Received transfusion of blood products (including platelets or red blood cells) or administration 
of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte-
macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks before 
study Day 1. 
35. Known psychiatric or substance abuse disorders that would interfere with cooperation with the 
requirements of the trial. 
36. Pregnant or breastfeeding or expecting to conceive children within the projected duration of the 
trial, starting with the screening visit through 120 days after the last dose of study treatment. 
37. Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
Investigational product, dosage, and mode of administration: Mirvetuximab soravtansine–
containing combination regimens will be investigated: 
Regimen A (mirvetuximab soravtansine + bevacizumab): Mirvetuximab soravtansine will be 
given IV on Day 1 of a 21-day cycle (Q3W); bevacizumab will be administered IV after completion of 
the mirvetuximab soravtansine infusion.  
Regimen B (mirvetuximab soravtansine + carboplatin): Mirvetuximab soravtansine will be given 
IV on Day 1; carboplatin will be administered IV after completion of the mirvetuximab soravtansine 
infusion; cycles will repeat every 21 days (Q3W). 
Regimen C (mirvetuximab soravtansine + pegylated liposomal doxorubicin): Mirvetuximab 
soravtansine will be given IV on Day 1; pegylated liposomal doxorubicin will be administered IV after 
completion of the mirvetuximab soravtansine infusion; cycles will repeat every 28 days (Q4W). 
Regimen D (mirvetuximab soravtansine + pembrolizumab): Mirvetuximab soravtansine will be 
given IV on Day 1; pembrolizumab will be administered IV after completion of the mirvetuximab 
soravtansine infusion; cycles will repeat every 21 days (Q3W).  
 
 
 
Regimen E (mirvetuximab soravtansine + bevacizumab + carboplatin): Mirvetuximab 
soravtansine will be given IV on Day 1 of a 21-day cycle (Q3W). Bevacizumab will be administered 
IV after completion of the mirvetuximab soravtansine infusion on Day 1 of a 21-day cycle (Q3W). 
Carboplatin will be administered IV after completion of the bevacizumab infusion; cycles will repeat 
every 21 days (Q3W). 
For all dosing regimens, the dose of mirvetuximab soravtansine will be calculated using AIBW. 
Duration of treatment: The period of observation extends from the time the patient receives the first 
dose of study treatment until the final follow-up study visit. Patients will continue to receive study 
treatment until they develop PD per RECIST Version 1.1, unacceptable toxicity, or withdraw consent, 
whichever comes first, or until the Sponsor terminates the study. Pembrolizumab (Regimen D) will be 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
21 
continued for up to 2 years. Patients who discontinue study drug for reasons other than PD will be 
followed until PD, start of new anti-cancer therapy, or death, whichever occurs first. 
Statistical methods: All statistical analyses will be performed using the most recently released SAS 
statistical software, unless otherwise noted. Patient disposition, patient demographics, and baseline 
characteristics will be tabulated. Pharmacokinetic parameters and plasma concentrations will also be 
presented (if available).  
No formal interim analysis is planned for this study. However, a review of safety data and available 
preliminary PK data will be conducted by the CRC upon completion of each Dose Escalation Cohort.  
A statistical analysis plan will fully describe the planned analyses for this study.  
Sample size: Ascending doses of mirvetuximab soravtansine and combination therapy will be 
evaluated to identify the MTD for each of the four doublet combination regimens. The actual number of 
patients accrued during the Dose Escalation phase will be determined largely by the findings observed 
during the course of their treatment. Regimen A (mirvetuximab soravtansine + bevacizumab) and 
Regimen D (mirvetuximab soravtansine + pembrolizumab) are expected to enroll 16 patients, whereas 
Regimen B (mirvetuximab soravtansine + carboplatin) and Regimen C (mirvetuximab soravtansine + 
pegylated liposomal doxorubicin) are expected to enroll 22 patients. Additional patients will be recruited 
into each regimen to ensure that 10 patients are treated at the MTD. Overall, the Dose Escalation 
phase of the study is expected to enroll approximately 76 to 120 patients.  
Following MTD determination, there will be a Dose Expansion phase for Regimens A and D.  
Regimen A (mirvetuximab soravtansine + bevacizumab): 
Patients enrolled in the Dose Expansion phase will be assigned to three Dose Expansion Cohorts 
according to prior exposure to bevacizumab as follows: 1) Dose Expansion Cohort 1: bevacizumab 
naïve; 2) Dose Expansion Cohort 2: bevacizumab pretreated; and 3) Dose Expansion Cohort 3: with 
one to three prior therapies including one prior therapy with bevacizumab (per Protocol Amendment 5).  
For the bevacizumab-naïve Cohort (Cohort 1), assuming a response rate of 55%, there is a 94.2% 
probability of detecting at least 8 responders if 20 patients are recruited. The response rate assumption 
is based on an ORR of 53% observed with the standard of care therapy of paclitaxel in combination 
with bevacizumab in patients with platinum-resistant EOC. 
For the bevacizumab-pretreated Cohort (Cohort 2), assuming a response rate of 50%, there is a 91.2% 
probability of detecting at least 14 responders if 35 patients are recruited.  
For the bevacizumab expansion Cohort (Cohort 3), assuming a response rate of 50%, there is a 95.4% 
probability of detecting at least 24 responders if 60 patients are recruited. In addition, the 90% 
confidence interval for true ORR is given in the table below if the observed number of responders is 
20 to 40 of 60 patients. 
 
 
Responses Observed, 60 Patients 
90% Exact Confidence Interval for True ORR 
20/60 (33%) 
(23%, 45%) 
21/60 (35%) 
(25%, 46%) 
22/60 (37%) 
(26%, 48%) 
23/60 (38%) 
(28%, 50%) 
24/60 (40%) 
(29%, 51%) 
25/60 (42%) 
(31%, 53%) 
26/60 (43%) 
(32%, 55%) 
27/60 (45%) 
(34%, 56%) 
28/60 (47%) 
(36%, 58%) 
29/60 (48%) 
(37%, 60%) 
30/60 (50%) 
(39%, 61%) 
31/60 (52%) 
(40%, 63%) 
32/60 (53%) 
(42%, 64%) 
33/60 (55%) 
(44%, 66%) 
34/60 (57%) 
(45%, 68%) 
35/60 (58%) 
(47%, 69%) 
36/60 (60%) 
(49%, 71%) 
37/60 (62%) 
(50%, 72%) 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
22 
38/60 (63%) 
(52%, 74%) 
39/60 (65%) 
(54%, 75%) 
40/60 (67%) 
(55%, 77%) 
Regimen D (mirvetuximab soravtansine + pembrolizumab): 
In the Dose Expansion phase for Regimen D, a total of 35 patients will be enrolled at FRα > 50% of 
tumor staining at intensity ≥ 2+ and 11 patients with a FRα 25% to 49% of tumor staining at intensity 
≥ 2+. Assuming a response rate of 50%, there is a 91.2% probability of detecting at least 14 
responders if 35 patients are recruited. In addition, the 90% confidence interval for true ORR is given in 
the table below if the observed number of responders is 12 to 18 of 35 patients. 
Responses Observed, 35 Patients 
90% Exact Confidence Interval for True ORR 
12/35 (34%) 
(21%, 50%) 
13/35 (37%) 
(24%, 52%) 
14/35 (40%) 
(26%, 55%) 
15/35 (43%) 
(29%, 58%) 
16/35 (46%) 
(31%, 61%) 
17/35 (49%) 
(34%, 64%) 
18/35 (51%) 
(36%, 66%) 
Regimen E (mirvetuximab soravtansine + bevacizumab + carboplatin): 
In Regimen E (Triplet), approximately 50 patients will be enrolled to ensure that 40 patients will be 
treated at the MTD. Assuming a response rate of 60%, there is a 92.6% probability of detecting at least 
20 responders if 40 patients are recruited. In addition, the 90% confidence interval for true ORR is 
given in the table below if the observed number of responders is 20 to 26 of 40 patients. 
Responses Observed, 40 Patients 
90% Exact Confidence Interval for True ORR 
20/40 (50%) 
(36%, 64%) 
21/40 (52.5%) 
(38%, 66%) 
22/40 (55%) 
(41%, 69%) 
23/40 (57.5%) 
(43%, 71%) 
24/40 (60%) 
(46%, 73%) 
25/40 (62.5%) 
(48%, 75%) 
26/40 (65%) 
(51%, 77%) 
Overall, the Dose Expansion phase is expected to enroll up to 211 patients. Assuming that 
approximately 90% of enrolled patients in the Dose Expansion phase will be evaluable, the study is 
expected to accrue approximately 311 to 355 patients. 
 
 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
23 
TABLE OF CONTENTS 
SPONSOR SIGNATURE PAGE ....................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................4 
PROTOCOL SYNOPSIS ................................................................................................................8 
TABLE OF CONTENTS ...............................................................................................................23 
LIST OF TABLES .........................................................................................................................30 
LIST OF FIGURES .......................................................................................................................32 
1. 
INTRODUCTION ......................................................................................................33 
1.1. 
Target Background .....................................................................................................33 
1.2. 
Mirvetuximab Soravtansine (IMGN853) ...................................................................33 
1.3. 
Epithelial Ovarian Cancer ...........................................................................................34 
1.4. 
Current Therapies .......................................................................................................35 
1.4.1. 
Bevacizumab ...............................................................................................................35 
1.4.2. 
Carboplatin .................................................................................................................35 
1.4.3. 
Topotecan ...................................................................................................................36 
1.4.4. 
Pegylated Liposomal Doxorubicin .............................................................................36 
1.5. 
Investigational Therapies ............................................................................................37 
1.5.1. 
Pembrolizumab ...........................................................................................................37 
1.6. 
Nonclinical Studies of Mirvetuximab Soravtansine ...................................................37 
1.6.1. 
Pharmacology .............................................................................................................37 
1.6.2. 
Pharmacokinetics ........................................................................................................38 
1.6.3. 
Toxicology ..................................................................................................................38 
1.7. 
Clinical Studies of Mirvetuximab Soravtansine .........................................................39 
1.7.1. 
First-in-Human Phase 1 Study: Study IMGN853-0401 .............................................39 
1.8. 
Rationale for the Starting Dose...................................................................................39 
1.8.1. 
Mirvetuximab Soravtansine ........................................................................................39 
1.8.2. 
Pembrolizumab ...........................................................................................................40 
1.9. 
Safety Rationale for the Triplet Combination ............................................................41 
1.10. 
Rationale for the Study Plan .......................................................................................41 
1.10.1. 
Rationale for FRα Expression Levels .........................................................................43 
2. 
TRIAL OBJECTIVES AND ENDPOINTS ...............................................................44 
2.1. 
Primary Objectives .....................................................................................................44 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
24 
2.1.1. 
Dose Escalation (Regimens A Through D) ................................................................44 
2.1.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) ................................44 
2.2. 
Primary Endpoints ......................................................................................................44 
2.2.1. 
Dose Escalation (Regimens A Through D) ................................................................44 
2.2.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) ................................44 
2.3. 
Secondary Objectives .................................................................................................44 
2.4. 
Secondary Endpoints ..................................................................................................45 
2.5. 
Exploratory Objectives ...............................................................................................45 
2.6. 
Exploratory Endpoints ................................................................................................46 
3. 
STUDY POPULATION .............................................................................................46 
3.1. 
Inclusion Criteria ........................................................................................................46 
3.1.1. 
Inclusion Criteria for All Patients (Dose Escalation and Dose Expansion, 
Regimen-Specific) ......................................................................................................46 
3.1.2. 
Exclusion Criteria .......................................................................................................49 
3.1.2.1. 
Additional Exclusion Criteria for Regimen A and Regimen E ..................................51 
3.1.2.2. 
Additional Exclusion Criteria for Regimen C ............................................................51 
3.1.2.3. 
Additional Exclusion Criteria for Regimen D ............................................................51 
4. 
INVESTIGATIONAL PLAN .....................................................................................52 
4.1. 
Study Design ...............................................................................................................52 
4.1.1. 
Overview and Schema ................................................................................................52 
4.1.2. 
Cohort Review Committee .........................................................................................54 
4.1.3. 
Dose Escalation Guidelines ........................................................................................54 
4.1.3.1. 
Dose Levels and Regimens .........................................................................................54 
4.1.3.2. 
Dose Escalation Rules (3 + 3 Design) ........................................................................56 
4.1.4. 
Definition of Dose-Limiting Toxicity ........................................................................57 
4.1.5. 
Dose Expansion Phase ................................................................................................58 
5. 
STUDY TREATMENT ..............................................................................................60 
5.1. 
Description of Study Treatment ..................................................................................60 
5.2. 
Mirvetuximab Soravtansine Packaging ......................................................................60 
5.3. 
Storage, Handling, and Accountability .......................................................................60 
5.4. 
Study Treatment Compliance .....................................................................................61 
5.5. 
Assignment of Patient Number ...................................................................................61 
5.5.1. 
Enrolled Patient Definition .........................................................................................61 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
25 
5.5.2. 
Patient Assignment to Dosing Regimens ...................................................................62 
5.6. 
Blinding ......................................................................................................................62 
5.7. 
Study Treatment Administration ................................................................................62 
5.7.1. 
Study Treatment Overview and Schedule ..................................................................62 
5.8. 
Study Drug Preparation and Administration ..............................................................62 
5.8.1. 
Premedication for Study Treatment ............................................................................62 
5.8.2. 
Prophylactic Use of Corticosteroid Eye Drops ...........................................................62 
5.8.3. 
Lubricating Artificial Tears ........................................................................................63 
5.8.4. 
Preparation and Administration of Mirvetuximab Soravtansine ................................63 
5.8.4.1. 
Calculation for Adjusted Ideal Body Weight .............................................................63 
5.8.4.2. 
Preparation of Mirvetuximab Soravtansine ................................................................63 
5.8.4.3. 
Administration of Mirvetuximab Soravtansine ..........................................................63 
5.8.5. 
Preparation and Administration of Bevacizumab .......................................................64 
5.8.6. 
Preparation and Administration of Carboplatin ..........................................................64 
5.8.7. 
Preparation and Administration of Pegylated Liposomal Doxorubicin .....................64 
5.8.8. 
Preparation and Administration of Pembrolizumab ...................................................64 
5.9. 
Monitoring and Management of Adverse Events .......................................................65 
5.9.1. 
Potential Infusion-Related Reactions .........................................................................65 
5.9.2. 
Monitoring and Management of Treatment-Emergent Ocular Disorders ..................66 
5.9.2.1. 
Monitoring of Potential Ocular Disorders ..................................................................66 
5.9.2.2. 
Management Guidelines for Ocular Disorders ...........................................................67 
5.9.3. 
Monitoring of Non-infectious Pneumonitis After Administration of Study 
Treatment ....................................................................................................................69 
5.9.4. 
Monitoring and Management of Diarrhea After Administration of Study 
Treatment ....................................................................................................................70 
5.9.4.1. 
Mirvetuximab Soravtansine–Associated Diarrhea .....................................................70 
5.9.4.2. 
Pembrolizumab-Associated Diarrhea and/or Colitis ..................................................71 
5.9.4.3. 
Diarrhea Associated With Mirvetuximab Soravtansine and Pembrolizumab ............71 
5.9.5. 
Monitoring and Management of Nausea and Vomiting After Administration 
of Study Treatment .....................................................................................................71 
5.9.6. 
Monitoring of Bevacizumab-Associated Posterior Reversible 
Encephalopathy Syndrome .........................................................................................72 
5.9.7. 
Monitoring and Management of Bevacizumab-Associated Hypertension .................72 
5.9.8. 
Monitoring and Management of Bevacizumab-Associated Proteinuria .....................72 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
26 
5.9.9. 
Monitoring and Management of Bevacizumab-Associated Bleeding ........................73 
5.9.10. 
Monitoring and Management of Bevacizumab-Associated Gastrointestinal 
Fistula/Perforation ......................................................................................................73 
5.9.11. 
Monitoring and Management of Peripheral Neuropathy ............................................73 
5.9.12. 
Monitoring and Management of Pembrolizumab-Associated Type 1 
Diabetes Mellitus ........................................................................................................75 
5.9.13. 
Monitoring and Management of Pembrolizumab-Associated Hypophysitis ..............75 
5.9.14. 
Monitoring and Management of Pembrolizumab-Associated 
Hyperthyroidism or Hypothyroidism .........................................................................75 
5.9.15. 
Monitoring and Management of Pembrolizumab-Associated Hepatic 
Adverse Events ...........................................................................................................76 
5.9.16. 
Monitoring and Management of Pembrolizumab-Associated Renal Failure or 
Nephritis .....................................................................................................................76 
5.10. 
Treatment Guidelines ..................................................................................................76 
5.10.1. 
Re-treatment Criteria ..................................................................................................76 
5.10.2. 
Follow-up for Dose-Limiting Toxicities and Adverse Events Leading to 
Discontinuation ...........................................................................................................77 
5.10.3. 
Criteria for Re-initiation of Study Treatment After Occurrence of a Dose-
Limiting Toxicity ........................................................................................................78 
5.10.4. 
Dose Modification Guidelines ....................................................................................78 
5.10.4.1. 
Mirvetuximab Soravtansine Dose Reduction After a Dose-Limiting Toxicity ..........78 
5.10.4.2. 
Bevacizumab Dose Modification Guidelines .............................................................78 
5.10.4.3. 
Pegylated Liposomal Doxorubicin Dose Modification Guidelines for 
Non-hematologic Adverse Events ..............................................................................79 
5.10.4.4. 
Carboplatin Dose Modification Guidelines ................................................................80 
5.10.4.5. 
Dose Modification and Toxicity Management for Immune-Related Adverse 
Events Associated With Pembrolizumab ....................................................................80 
5.10.4.6. 
Dose Modification and Toxicity Management of Infusion Reactions Related 
to Pembrolizumab .......................................................................................................85 
5.10.4.7. 
Hierarchy of Dose Reductions/Discontinuations ........................................................88 
5.10.5. 
Discontinuation of Study Treatment Due to Adverse Events .....................................90 
5.10.6. 
Additional Discontinuation Guidelines ......................................................................91 
5.10.6.1. 
Pegylated Liposomal Doxorubicin Discontinuation ...................................................91 
5.10.6.2. 
Bevacizumab Discontinuation ....................................................................................91 
5.10.6.3. 
Carboplatin Discontinuation .......................................................................................91 
5.10.6.4. 
Pembrolizumab Discontinuation ................................................................................91 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
27 
5.11. 
Removal of the Patient From the Study or From Study Drug Administration ...........93 
5.11.1. 
Replacement of Patients Who Are Withdrawn Before the End of Cycle 1 ................94 
5.12. 
Period of Observation .................................................................................................94 
5.13. 
Concomitant Medications and Procedures .................................................................94 
5.13.1. 
Antiemetic and Antidiarrheal Medications .................................................................94 
5.13.2. 
Folate-Containing Vitamins........................................................................................94 
5.13.3. 
Antineoplastic Therapy ...............................................................................................94 
5.13.4. 
Hematopoietic Growth Factors ...................................................................................95 
5.13.5. 
Medications Metabolized Through Cytochrome P450 3A .........................................95 
5.13.6. 
Vaccinations (Regimen D Only) ................................................................................95 
5.13.7. 
Systemic Steroids (Regimen D Only).........................................................................95 
5.13.8. 
Other Concomitant Medications .................................................................................95 
5.14. 
Overdose and Medication Error ..................................................................................96 
5.14.1. 
Overdose .....................................................................................................................96 
5.14.2. 
Medication Error .........................................................................................................96 
6. 
PHARMACOKINETIC AND IMMUNOGENEICITY ASSESSMENTS ................96 
6.1. 
Pharmacokinetic Assessments ....................................................................................96 
6.1.1. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen A 
(Mirvetuximab Soravtansine + Bevacizumab) ...........................................................97 
6.1.2. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen B 
(Mirvetuximab Soravtansine + Carboplatin) ..............................................................98 
6.1.3. 
Pharmacokinetic Assessments for 4-Week Cycle Regimen C (Mirvetuximab 
Soravtansine + Pegylated Liposomal Doxorubicin) ...................................................99 
6.1.4. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen D 
(Mirvetuximab Soravtansine + Pembrolizumab)........................................................99 
6.1.5. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen E 
(Mirvetuximab Soravtansine + Bevacizumab + Carboplatin) ..................................100 
6.2. 
Immunogenicity Assessments of Mirvetuximab Soravtansine .................................101 
7. 
TRANSLATIONAL RESEARCH STUDIES ..........................................................101 
7.1. 
Correlation Between FRα Expression and Mirvetuximab Soravtansine Anti-
tumor Activity ...........................................................................................................101 
7.1.1. 
Evaluation of FRα Expression in Tumor Tissue During Dose Escalation and 
Dose Expansion ........................................................................................................102 
7.2. 
Exploratory Biomarker Studies ................................................................................102 
7.2.1. 
Potential Markers of Drug Response ........................................................................103 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
28 
7.2.2. 
Potential Markers of Drug Resistance ......................................................................103 
7.2.3. 
Potential Mechanism of Synergy Between Mirvetuximab Soravtansine and 
Pembrolizumab .........................................................................................................103 
8. 
STUDY PROCEDURES ..........................................................................................104 
8.1. 
Informed Consent .....................................................................................................104 
8.2. 
Inclusion and Exclusion Criteria ..............................................................................104 
8.3. 
Confirmation of Disease Diagnosis ..........................................................................104 
8.4. 
Demographic/Medical History .................................................................................104 
8.5. 
Physical Examination, Weight, and Height ..............................................................104 
8.6. 
Vital Signs ................................................................................................................104 
8.7. 
Electrocardiogram .....................................................................................................105 
8.8. 
Pulse Oximetry .........................................................................................................105 
8.9. 
Pulmonary Function Tests ........................................................................................105 
8.10. 
Laboratory Assessments ...........................................................................................105 
8.10.1. 
Clinical Laboratory Panels .......................................................................................106 
8.11. 
Pregnancy Screen ......................................................................................................106 
8.12. 
Eastern Cooperative Oncology Group Performance Status ......................................106 
8.13. 
Radiologic Imaging ..................................................................................................106 
8.14. 
Echocardiogram/Multigated Acquisition Scan .........................................................107 
8.15. 
Tumor Response Assessment ...................................................................................107 
8.15.1. 
RECIST and CA125 .................................................................................................107 
8.15.2. 
Immune-Related RECIST (Regimen D Only) ..........................................................107 
8.16. 
Eligibility Based on FRα Expression ........................................................................108 
8.17. 
Biopsy of Tumor (Regimen D Only) ........................................................................108 
9. 
ASSESSMENT OF SAFETY ...................................................................................108 
9.1. 
Recording Adverse Events .......................................................................................108 
9.1.1. 
Definition of Adverse Events ...................................................................................109 
9.1.1.1. 
Adverse Event ...........................................................................................................109 
9.1.1.2. 
Serious Adverse Event ..............................................................................................109 
9.1.1.3. 
Adverse Events of Special Interest ...........................................................................110 
9.1.1.4. 
Mirvetuximab Soravtansine ......................................................................................110 
9.1.1.5. 
Pembrolizumab .........................................................................................................110 
9.1.2. 
Classification of Adverse Events ..............................................................................111 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
29 
9.2. 
Reporting of Adverse Events ....................................................................................112 
9.2.1. 
Reporting of Serious Adverse Events and/or Adverse Events of Special 
Interest ......................................................................................................................112 
9.2.2. 
Reporting of Disease Progression .............................................................................113 
9.2.3. 
Reporting a Pregnancy ..............................................................................................113 
10. 
STUDY ACTIVITIES ..............................................................................................114 
10.1. 
Screening Visit ..........................................................................................................114 
10.1.1. 
Standard of Care Assessments ..................................................................................114 
10.2. 
End of Treatment Visit .............................................................................................114 
10.3. 
Follow-up Assessments ............................................................................................115 
10.3.1. 
Safety Follow-up ......................................................................................................115 
10.3.2. 
Response Follow-up .................................................................................................115 
11. 
STATISTICAL METHODS .....................................................................................115 
11.1. 
Sample Size ..............................................................................................................115 
11.2. 
Pharmacokinetic Analyses ........................................................................................117 
11.3. 
Immunogenicity Assessment ....................................................................................118 
11.4. 
Safety Analyses ........................................................................................................118 
11.5. 
Anti-tumor Activity ..................................................................................................118 
12. 
QUALITY CONTROL AND ASSURANCE ..........................................................119 
13. 
ADMINISTRATIVE CONSIDERATIONS, STUDY MONITORING, AND 
DATA MANAGEMENT .........................................................................................119 
13.1. 
Investigators and Study Administrative Structure ....................................................119 
13.2. 
Institutional Review Board or Independent Ethics Committee Approval ................119 
13.3. 
Ethical Conduct of the Study ....................................................................................120 
13.4. 
Patient Information and Consent ..............................................................................120 
13.5. 
Patient Confidentiality ..............................................................................................121 
13.6. 
Study Monitoring ......................................................................................................121 
13.7. 
Case Report Forms and Study Reports .....................................................................121 
13.8. 
Critical Documents ...................................................................................................121 
13.9. 
Protocol Violations/Deviations .................................................................................122 
13.10. 
End of Study .............................................................................................................123 
13.11. 
Study Termination ....................................................................................................123 
13.11.1. 
Study Termination ....................................................................................................123 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
30 
13.11.2. 
Site Termination .......................................................................................................123 
13.12. 
Access to Source Documentation .............................................................................123 
13.13. 
Data Generation and Analysis ..................................................................................123 
13.14. 
Retention of Data ......................................................................................................124 
13.15. 
Financial Disclosure .................................................................................................124 
13.16. 
Publication and Disclosure Policy ............................................................................124 
14. 
LIST OF REFERENCES ..........................................................................................125 
APPENDIX A. SCHEDULE OF CLINICAL ASSESSMENTS – REGIMENS A, B, 
AND E ......................................................................................................................130 
APPENDIX B. SCHEDULE OF CLINICAL ASSESSMENTS – REGIMEN C ....................133 
APPENDIX C. SCHEDULE OF CLINICAL ASSESSMENTS – REGIMEN D ....................136 
APPENDIX D. BLOOD SAMPLE COLLECTION FOR PHARMACOKINETICS, 
IMMUNOGENICITY, AND BIOMARKER ASSESSMENTS – 
REGIMENS A, B, C, D, AND E ..............................................................................139 
APPENDIX E. PEMBROLIZUMAB BACKGROUND ..........................................................140 
APPENDIX F. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS SCALE .......................................................................142 
APPENDIX G. RESPONSE DEFINITION (RECIST VERSION 1.1) ....................................142 
APPENDIX H. GYNECOLOGIC CANCER INTERGROUP CRITERIA FOR 
EVALUATION OF CA125 ......................................................................................147 
APPENDIX I. RESPONSE DEFINITION (IMMUNE-RELATED RECIST) 
(REGIMEN D ONLY) .............................................................................................148 
APPENDIX J. CALVERT FORMULA FOR CARBOPLATIN DOSING ..............................150 
APPENDIX K. BODY SURFACE AREA CALCULATION..................................................150 
APPENDIX L. ADJUSTED IDEAL BODY WEIGHT CALCULATION ..............................151 
APPENDIX M. COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS 
VERSION 4.03 GRADING FOR SELECTED ADVERSE EVENTS ....................152 
APPENDIX N. EXAMPLES OF SENSITIVE IN VIVO CYTOCHROME P450 
SUBSTRATES AND CYTOCHROME P450 SUBSTRATES WITH 
NARROW THERAPEUTIC RANGE (28 JULY 2011) ..........................................153 
APPENDIX O. SCHEMA FOR ADMINISTRATION OF STUDY-REQUIRED EYE 
DROPS .....................................................................................................................153 
 
LIST OF TABLES 
Table 1: 
Planned Dose Levels (Dose Escalation) for Regimen A (Mirvetuximab 
Soravtansine + Bevacizumab) ....................................................................................54 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
31 
Table 2: 
Planned Dose Levels (Dose Escalation) for Regimen B (Mirvetuximab 
Soravtansine + Carboplatin) .......................................................................................55 
Table 3: 
Planned Dose Levels (Dose Escalation) for Regimen C (Mirvetuximab 
Soravtansine + Pegylated Liposomal Doxorubicin) ...................................................55 
Table 4: 
Planned Dose Levels (Dose Escalation) for Regimen D (Mirvetuximab 
Soravtansine + Pembrolizumab) .................................................................................55 
Table 5: 
Dose-Limiting Toxicity Definitions ...........................................................................58 
Table 6: 
Planned Doses for Regimen E ....................................................................................60 
Table 7: 
Management Guidelines for Potential Infusion-Related Reactions ............................66 
Table 8: 
Schedule for Ophthalmic Assessments .......................................................................67 
Table 9: 
Management of Ocular Disorders ...............................................................................68 
Table 10: Management of Non-infectious Pneumonitis .............................................................69 
Table 11: Management of Nausea and Vomiting .......................................................................71 
Table 12: Management of Hypertension After Bevacizumab Administration ............................72 
Table 13: Management of Bevacizumab-Associated Proteinuria ...............................................72 
Table 14: Management Guidelines for Peripheral Neuropathy ..................................................74 
Table 15: Mirvetuximab Soravtansine Dose Modification Guidelines ......................................78 
Table 16: Bevacizumab Dose Modification Guidelines .............................................................79 
Table 17: Dose Modification Guidelines for Pegylated Liposomal Doxorubicin for 
Non-hematologic Adverse Events ..............................................................................79 
Table 18: Pegylated Liposomal Doxorubicin Dose Reduction for Hematologic Adverse 
Events .........................................................................................................................79 
Table 19: Pegylated Liposomal Doxorubicin Dose Modification Guidelines for Hand 
and Foot Syndrome and Mucositis .............................................................................80 
Table 20: Dose Modification Guidelines for Carboplatin ..........................................................80 
Table 21: Dose Modification and Toxicity Management Guidelines for Immune-
Related Adverse Events Associated With Pembrolizumab ........................................82 
Table 22: Pembrolizumab Infusion Reaction Dose Modification and Treatment 
Guidelines ...................................................................................................................86 
Table 23: Agent to be Dose Reduced/Discontinued First on the Basis of Reported 
Compound-Specific Treatment-Related Adverse Events ...........................................89 
Table 24: Adverse Events Requiring Permanent Discontinuation of Bevacizumab ..................91 
Table 25: Adverse Events Requiring Discontinuation of Pembrolizumab .................................93 
Table 26: Vital Sign Measurements ..........................................................................................105 
Table 27: Clinical Laboratory Tests .........................................................................................106 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
32 
Table 28: Adverse Event Severity ............................................................................................111 
Table 29: Adverse Event Casual Relationship to Study Drug ..................................................112 
 
LIST OF FIGURES 
Figure 1: Study Design Schema .....................................................................................................53 
 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
33 
1. 
INTRODUCTION 
1.1. 
Target Background 
Folate receptor alpha (FRα) (gene symbol FOLR1) is a glycophosphatidylinositol-linked protein 
that shows limited normal tissue expression and high expression in several solid tumors 
(Kelemen 2006), most notably serous epithelial ovarian cancer (EOC) (Miotti 1987, 
O’Shannessy 2013). FRα binds and internalizes folate, which is an essential co-factor for one-
carbon transfer reactions that are required for DNA and RNA synthesis, cell growth, and 
proliferation. Marked upregulation of FRα occurs during neonatal development and in cancer, 
suggesting that the receptor functions primarily under conditions of high folate demand. In 
contrast, normal adult tissues generally lack FRα expression and employ alternative transporters 
such as folate receptor β, reduced folate carrier, and proton-coupled folate transporter for folate 
uptake (Weitman 1992, Mantovani 1994, Elnakat 2004).  
Several additional studies have further validated FRα as a target in serous ovarian cancer. First, 
quantitative polymerase chain reaction studies show ubiquitous FRα messenger RNA (mRNA) 
expression in serous ovarian cancer (Hoskins 2001, Hough 2001), and high levels of FRα mRNA 
correlate with poor response to chemotherapy and decreased disease-free survival (Chen 2012). 
Second, both Kalli et al and Crane et al have demonstrated that recurrent tumors retain FRα 
expression comparably to primary tumors as shown by serial biopsy sampling and 
immunohistochemistry (IHC) (Kalli 2008, Crane 2012). Third, studies with FRα-specific 
imaging agents have demonstrated real-time FRα expression at primary and metastatic tumor 
sites (Fisher 2008, Garcia 2013, Garin-Chesa 1993, and van Dam 2011). Finally, a truncated 
form of FRα has been detected in ascites and blood of ovarian cancer patients (Basal 2009, 
Mantovani 1994), further confirming expression in this disease and suggesting that the receptor 
may serve as a circulating biomarker. Collectively, these data suggest that FRα is a promising 
target in solid tumors, particularly EOC. 
1.2. 
Mirvetuximab Soravtansine (IMGN853) 
Because of its tumor-specific expression and capacity to internalize small and large molecule 
ligands, FRα has emerged as a promising target for antibody-drug conjugate (ADC) therapy. 
ADCs combine the specificity of monoclonal antibodies (mAbs) to tumor antigens with the 
extraordinary cytotoxicity of maytansine derivatives, which are potent anti-microtubule agents 
that target proliferating cells. Mirvetuximab soravtansine, also known as IMGN853, is a targeted 
ADC that binds with high affinity to FRα, a glycophosphatidylinositol-linked protein that shows 
limited normal tissue expression and high expression in several solid tumors (Kelemen 2006), 
most notably serous EOC (Miotti 1987, O’Shannessy 2013). This ADC consists of a humanized 
anti-FRα mAb attached via a cleavable disulfide containing linker to the cytotoxic maytansinoid 
DM4. Maytansinoids are anti-mitotic agents that inhibit tubulin polymerization and microtubule 
assembly, resulting in cell cycle arrest and apoptosis. The antibody component of mirvetuximab 
soravtansine is composed of two immunoglobulin (Ig) G1 heavy chains of 447 amino acids and 
two kappa light chains of 218 amino acids and has a molecular weight of 145,676 Da 
(non-glycosylated form). Each antibody molecule is conjugated to an average of three to four 
molecules of DM4. 
In vitro studies have demonstrated that mirvetuximab soravtansine binds cell surface FRα with 
high apparent affinity (≤ 0.1 nM) and shows potent (50% inhibitory concentration [IC50] ≤ 1 nM) 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
34 
and selective cytotoxicity against tumor cells expressing FRα. Cytotoxic effects of mirvetuximab 
soravtansine in vitro correlate with the level of cell-surface expression of FRα. Mirvetuximab 
soravtansine demonstrates significant activity against FRα-positive tumor xenografts, with 
partial and complete remissions observed in ovarian models (Ab 2015). The in vitro and in vivo 
pharmacologic properties of mirvetuximab soravtansine, along with the high expression of FRα 
in EOC, provided the rationale for exploring mirvetuximab soravtansine in a clinical setting. 
1.3. 
Epithelial Ovarian Cancer  
This study will enroll patients with FRα-positive EOC. 
Epithelial ovarian cancer is the most lethal of gynecologic cancers worldwide. There are an 
estimated 22,240 new cases of ovarian cancer and 14,070 deaths expected in 2018 in the United 
States (US) (National Cancer Institute - SEER 2018), and in the European Union and North 
America, 89,113 new cases of ovarian cancer with 59,754 deaths are estimated 
(GLOBOCAN 2012). Because of the lack of effective screening tools and the non-specific nature 
of the presenting symptoms, more than 70% of patients with EOC are diagnosed with recurrent 
disease (Stage 3C and Stage 4) (Timmermans 2017). Late-stage EOC is rarely curable despite 
intensive adjuvant or neo-adjuvant chemotherapy and optimal surgical resection. Heintz et al 
reported the 5-year survival for patients with Stage 3C and Stage 4 disease as 32.5% and 18.6% 
respectively. Similarly, Timmermans et al reported that patients with recurrent disease have an 
expected 5-year survival rate of 24%. In patients who have developed platinum-resistant disease, 
the median overall survival is < 12 months (Naumann 2011). 
Key signs and symptoms of EOC at presentation include persistent bloating, pelvic or abdominal 
pain, urinary symptoms (urgency or frequency), decreased appetite, and feeling full quickly. 
Other symptoms can include fatigue, indigestion, constipation, back pain, pain with intercourse, 
and menstrual irregularities. Many of these symptoms are frequently seen in women who do not 
have EOC, making symptom-based diagnosis difficult.  
Risk factors associated with development of EOC include age (approximately 50% of women 
with EOC are > 63 years of age), weight (body mass index ≥ 30), germline BRCA1 and BRCA2 
mutations (in about 15% of ovarian cancer [Risch 2001]), and reproductive history (eg, increased 
risk with fertility treatment and decreased risk with birth control pills 
[American Cancer Society 2016]).  
Ovarian tumors are derived from one of three common cell types: epithelial cells (accounting for 
90% of all cases [Rosen 2009]), germ cells, or stromal cells. Recent studies indicate that ovarian, 
peritoneal, and fallopian tube cancers are not distinct entities, but represent a spectrum of 
diagnoses that originate in the mullerian tissue. Primary fallopian tube carcinoma and peritoneal 
cancers are now included in the ovarian cancer staging classification (Cobb 2015, Grant 2010, 
Naumann 2011, O’Shannessy 2013) and are considered to be part of EOC with the same 
treatment and outcomes. 
Epithelial ovarian cancer is staged according to the International Federation of Gynecology and 
Obstetrics staging system. At Stage I, the tumor is confined to either one or both ovaries or 
fallopian tubes, the ovary capsule may be ruptured, and there could be tumor on the ovarian 
surface; malignant cells may be found in the ascites or peritoneal washings. At Stage II, the 
tumor involves one or both ovaries or fallopian tubes with pelvic extension (below the pelvic 
brim) or primary peritoneal cancer. At Stage III, the tumor may involve one or both ovaries, or 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
35 
fallopian tubes, or primary peritoneal cancer with either cytologically or histologically confirmed 
metastasis to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph 
nodes. Stage IV consists of distant metastasis, excluding peritoneal metastases (Prat 2015). 
Epithelial ovarian cancer is also classified by histology and grade. Serous ovarian carcinomas, 
which account for 75% of EOC tumors, are graded as either low-grade serous ovarian carcinoma 
(approximately 3% of all serous EOC) or high-grade serous ovarian carcinoma (HGSOC) 
(approximately 97% of all serous EOC [Bergstrom 2017]). Other histologic subtypes (eg, 
endometrioid) are graded 1 through 3, high differentiation through low differentiation, 
respectively (ASCO 2017). HGSOCs are associated with the poorest outcomes. Despite a typical 
rapid response to frontline platinum-based therapy, HGSOC is associated with rapid relapse and 
development of platinum resistance (Alkema 2016).  
1.4. 
Current Therapies 
Current management of advanced-stage EOC typically involves surgical de-bulking either before 
or after platinum-based chemotherapy (commonly carboplatin and paclitaxel). However, most 
patients will experience recurrence of disease (Garcia 2013). Patients who relapse > 6 months 
after platinum-based treatments are considered platinum sensitive and typically will be re-treated 
with a platinum-based combination regimen, with or without maintenance therapy. Patients who 
relapse ≤ 6 months after treatment are considered platinum-resistant. Almost all platinum-
sensitive patients will eventually develop resistance, at which point they are considered to have 
acquired secondary platinum-resistant disease. Patients with platinum-resistant disease may be 
treated with a variety of agents, including topotecan, bevacizumab, and pegylated liposomal 
doxorubicin alone or in combination with weekly paclitaxel.  
1.4.1. 
Bevacizumab 
Bevacizumab is a humanized mAb that binds to vascular endothelial growth factor A and has 
antiangiogenic activity. Bevacizumab is approved for use in combination with chemotherapy 
both in the EOC frontline setting (Burger 2011, Perren 2012) and in the platinum-resistant 
setting with up to 2 prior treatments (Pujade-Lauraine 2014). In two frontline trials (GOG218 
and ICON7) in EOC, the addition of bevacizumab to carboplatin and paclitaxel, followed by 
maintenance therapy with bevacizumab, was shown to significantly prolong progression-free 
survival (PFS) compared with carboplatin and paclitaxel (GOG218: 14.1 vs 10.3 months; 
ICON7: 19.0 vs 17.3 months) (Burger 2011, Perren 2012). In patients with platinum-sensitive 
disease at first relapse, the addition of bevacizumab to carboplatin and gemcitabine demonstrated 
a PFS advantage of 4 months. The AURELIA trial demonstrated a 3.3-month improvement in 
PFS for patients who received bevacizumab in combination with chemotherapy, followed by 
maintenance with bevacizumab, compared with those who received chemotherapy alone 
(Pujade-Lauraine 2014). 
1.4.2. 
Carboplatin 
Carboplatin is often used in relapsed ovarian cancer that remains potentially platinum sensitive, 
based on a platinum-free interval of > 6 months, and may be used as a single agent or in 
combination (Aghajanian 2012, Raja 2012). Conventional frontline chemotherapy for EOC 
consists of paclitaxel and carboplatin administered every 3 weeks (Q3W) for six cycles. 
Although the outcomes are comparable, carboplatin in combination with docetaxel or pegylated 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
36 
liposomal doxorubicin has a better tolerability profile than that of carboplatin in combination 
with paclitaxel. For instance, carboplatin and pegylated liposomal doxorubicin have been 
associated with a lower frequency of alopecia, neuropathies, hypersensitivity reactions, and 
arthralgia compared with the carboplatin and paclitaxel combination. Carboplatin in combination 
with pegylated liposomal doxorubicin has been evaluated in platinum-sensitive or partially 
sensitive patients with gynecological malignancies. Patients with platinum-sensitive EOC treated 
with this regimen had a lower frequency of alopecia, neuropathies, hypersensitivity reactions, 
and arthralgia compared with those treated with carboplatin in combination with paclitaxel. 
Carboplatin given at either AUC6 or AUC5 and pegylated liposomal doxorubicin administered at 
either 40 mg/m2 or 50 mg/m2 every 28 days resulted in objective response rates (ORRs) of 60% 
to 70%, PFS of 9.2 to 11.2 months, and median overall survival of 23 months in platinum-
sensitive or partially sensitive patients (Ferrero 2004, Vorobiof 2004). 
1.4.3. 
Topotecan 
Topotecan inhibits topoisomerase 1, leading to both single- and double-stranded DNA breaks 
that eventually promote apoptosis. Topotecan (administered once daily for the first 5 days of 
21-day cycles) was approved for treatment of EOC after failure of initial or subsequent 
chemotherapy. This approval was based on a Phase 3 trial that showed it to be at least as 
effective as paclitaxel, with a response rate of 21% versus 13%, and median PFS of 23 weeks 
versus 14 weeks, respectively (ten Bokkel Huinink 1997). Unfortunately, topotecan treatment led 
to severe bone marrow suppression, with 80% Grade 4 neutropenia, 25% Grade 4 
thrombocytopenia, and 41% Grade 3 or 4 anemia (ten Bokkel Huinink 1997). 
As such toxicities are often dose limiting, multiple clinical trials have studied alternative dosing 
schedules to improve the tolerability of topotecan treatment (Armstrong 2004, Hoskins 1998). 
For example, one Phase 2 trial tested the effect of the standard dosing of topotecan (1.5 mg/m2 
daily for the first 5 days of 21-day cycles) compared with an alternative dosing regimen (1.75 
mg/m2 once weekly for 4 weeks, repeated every 6 weeks) in patients with recurrent EOC. The 
alternative dosing regimen led to a lower response rate (9.6% compared with 22.6% in the 
standard dosing arm) but also decreased myelotoxicity (52% of patients had Grade 3 or 4 
granulocytopenia in comparison with 94% in the standard dosing arm) (Hoskins 1998). A 
subsequent Phase 2 trial tested the effect of yet another dosing schedule (1.5 mg/m2 daily for the 
first 3 days of 21-day cycles) (Markman 2000). Compared with historical controls, this 
alternative dosing regimen seemed to decrease the toxicity of topotecan. In a meta-analysis of 
various clinical trials, it was concluded that modification of the topotecan dose, and potentially 
the dosing schedule, can indeed reduce hematologic toxicity without decreasing the efficacy of 
the drug (Armstrong 2004). 
1.4.4. 
Pegylated Liposomal Doxorubicin 
Pegylated liposomal doxorubicin is approved as monotherapy for relapsed ovarian cancer 
(Pisano 2013) and has also been combined with carboplatin in the frontline setting with similar 
activity (Gladieff 2012). Studies with single-agent pegylated liposomal doxorubicin in patients 
with platinum-resistant ovarian cancer have yielded ORRs of approximately 10% to 20%. 
Palmar-plantar erythrodysesthesia (hand-foot syndrome [HFS]) and mucositis were the most 
commonly reported toxicities and the most common cause of dose reduction and treatment 
discontinuation (Pisano 2013). Decreased rates of HFS and stomatitis/mucositis and comparable 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
37 
response rates and outcomes have been observed when pegylated liposomal doxorubicin is 
administered at a dose of 40 mg/m2 every 28 days compared with the approved dose of 50 mg/m2 
given on a similar schedule (Pisano 2013). Pegylated liposomal doxorubicin administered in 
combination with various agents has demonstrated increased activity compared with pegylated 
liposomal doxorubicin alone. Pegylated liposomal doxorubicin in combination with oxaliplatin 
has been associated with an ORR of 60% to 70%, whereas ORRs of 30% to 40% have been 
observed in patients treated with pegylated liposomal doxorubicin in combination with 
gemcitabine, topotecan, paclitaxel, vinorelbine, or ifosfamide (Pisano 2013). The tolerability 
profile of these combinations was good, except for pegylated liposomal doxorubicin/topotecan, 
which was associated with unacceptable levels of hematologic toxicity. 
1.5. 
Investigational Therapies  
1.5.1. 
Pembrolizumab  
Pembrolizumab is a potent humanized IgG4 mAb with high specificity of binding to the 
programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell 
death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on nonclinical in 
vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD-1. 
Pembrolizumab has an acceptable nonclinical safety profile and is in clinical development as an 
intravenous (IV) immunotherapy for advanced malignancies. Pembrolizumab is indicated for the 
treatment of patients across several indications. For more details on specific indications, refer to 
the Appendix E. 
Refer to Appendix E and the approved labeling for detailed background information on 
pembrolizumab. 
1.6. 
Nonclinical Studies of Mirvetuximab Soravtansine  
1.6.1. 
Pharmacology 
Results of nonclinical pharmacology studies demonstrate the following that support single-agent 
and combination studies: 
• FRα has limited normal tissue expression and marked expression in epithelial tumors, 
particularly serous and EOCs and serous endometrial cancers, as assessed by IHC 
(Investigator Brochure). 
• In vitro studies demonstrated that mirvetuximab soravtansine binds cell surface FRα 
with apparent high affinity (≤ 0.1 nM) and shows potent (IC50 ≤ 1 nM) and selective 
cytotoxicity against cells expressing FRα. Mirvetuximab soravtansine–mediated 
cytotoxicity involves binding, internalization, and degradation of mirvetuximab 
soravtansine 3, which releases DM4. DM4 and a second catabolite, S-methyl-DM4, 
then inhibit tubulin polymerization and microtubule assembly, causing cell death. The 
lipophilic molecules S-methyl DM4 and DM4 can also diffuse to neighboring cells 
and induce bystander killing.  
• In vitro cytotoxicity studies suggest that cells sensitive to mirvetuximab soravtansine 
express higher levels of FRα and release 10- to 100-fold more cytotoxic maytansinoid 
than cells resistant to mirvetuximab soravtansine.  


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
38 
• Mirvetuximab soravtansine retains the inherent activities of its antibody moiety, 
M9346A, including binding affinity (apparent affinity ≤ 0.1 nM) and selectivity for 
FRα, capacity for uptake, internalization and degradation by FRα-positive target cells, 
and ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.  
• Mirvetuximab soravtansine demonstrates significant activity against FRα-positive 
xenografts. Partial and/or complete regressions in xenograft models of EOC were 
seen at doses of mirvetuximab soravtansine well below its maximum tolerated dose 
(MTD).  
• Mirvetuximab soravtansine shows significant in vivo efficacy against ovarian 
(IGROV-1, OVCAR-3, and OV-90 models) and non–small-cell lung carcinoma 
(NSCLC) (NCI-H2110 model) tumor xenografts.  
• Combination mirvetuximab soravtansine + bevacizumab is more efficacious than 
either agent administered as a monotherapy in ovarian (OV90 and IGROV-1) tumor 
xenografts and in an ovarian cancer patient–derived xenograft model (ST088). In the 
patient-derived xenograft model, the mirvetuximab soravtansine + bevacizumab 
combination is more efficacious than combination therapy consisting of paclitaxel + 
bevacizumab. 
• Combination mirvetuximab soravtansine + carboplatin is more efficacious than either 
agent administered as a monotherapy in the OV90 ovarian tumor xenograft model. 
Combination mirvetuximab soravtansine + carboplatin is more efficacious than 
carboplatin + paclitaxel in the model.  
• Combination mirvetuximab soravtansine + pegylated liposomal doxorubicin is more 
efficacious than either agent administered as a monotherapy in the ST088 ovarian 
cancer patient–derived xenograft model. 
Pharmacology studies are further detailed in the mirvetuximab soravtansine 
Investigator Brochure. 
1.6.2. 
Pharmacokinetics 
Nonclinical studies with mirvetuximab soravtansine cross-reactive (monkey) and non–cross-
reactive (mouse) species were conducted to define pharmacokinetic (PK) parameters and to 
determine the stability of the linker and impact of conjugation on antibody clearance. An 
additional PK study with free DM4 was conducted in monkeys. Pharmacokinetic studies 
demonstrated the stability of mirvetuximab soravtansine in circulation, showed clearance via a 
distribution phase lasting about 24 hours followed by a slower terminal elimination phase after 
IV administration, and suggested linear PK. These studies are further detailed in the 
mirvetuximab soravtansine Investigator Brochure.  
1.6.3. 
Toxicology 
Mirvetuximab soravtansine was evaluated for toxicity after a single IV injection in cross-reactive 
(monkey) and non–cross-reactive (mouse) species. Results of these studies supported the 
first-in-human (FIH) trial exploring the safety and tolerability of mirvetuximab soravtansine 
when administered Q3W to patients with advanced solid tumors. Potential risks suggested by 
these studies and by clinical experience with other maytansinoid ADCs include hematologic 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
39 
abnormalities, electrolyte alterations, injection site reactions, infusion reactions, 
immunogenicity, hepatic abnormalities, and peripheral neuropathy. Toxicology studies are 
further detailed in the mirvetuximab soravtansine Investigator Brochure. 
1.7. 
Clinical Studies of Mirvetuximab Soravtansine  
1.7.1. 
First-in-Human Phase 1 Study: Study IMGN853-0401 
The FIH Phase 1 study evaluated the safety, PK, and pharmacodynamics of single-agent 
mirvetuximab soravtansine in patients with EOC and other FRα-positive tumors. Mirvetuximab 
soravtansine was administered using two dosing schedules: Q3W (A) and on Days 1, 8, and 15 
of a 28-day cycle (B). Pharmacokinetic data and treatment-emergent adverse events (TEAEs) 
reported by patients enrolled in the dose escalation cohorts are listed in the 
Investigator Brochure.  
The recommended Phase 2 dose (R2PD) for single-agent mirvetuximab 
soravtansine administered Q3W was determined to be 6 mg/kg adjusted ideal body weight 
(AIBW). As of February 2018, mirvetuximab soravtansine had a 27% ORR (95% CI, 18.5%, 
37.1%) and median PFS of 4.2 months (95% CI, 3.7, 5.4 months) in the 96 patients with 
platinum-resistant EOC in the patient expansion cohort in Study 0401.  
The ORR was 47% (95% CI, 30.4%, 64.5%) and the median PFS was 6.7 months (95% CI, 4.1, 
8.3 months) in the subset of 36 patients with FRα-positive (medium/high expression [≥ 50% of 
cells with ≥ 2+ intensity]) platinum-resistant EOC with one to three prior regimens treated as 
part of a 96-patient Expansion Cohort in Study 0401 (clinical study report Table 16). Similarly, 
results of a pooled analysis of 113 patients showed an ORR of 30% (95% CI, 21.8%, 39.4%), a 
median PFS of 4.3 months (95% CI, 3.9, 5.4), and a median duration of response of 19.3 weeks 
(95% CI, 18, 34 weeks). 
Treatment-related adverse events (AEs) occurring in > 20% of patients in this cohort included 
diarrhea, blurred vision, fatigue, nausea, and increased aspartate aminotransferase (AST), and 
were mostly low grade. Blurred vision was likely related to the development of corneal 
keratopathy, transient microcysts that form in the corneal epithelium, causing temporary 
symptoms. 
1.8. 
Rationale for the Starting Dose  
1.8.1. 
Mirvetuximab Soravtansine  
The starting dose of mirvetuximab soravtansine in this Phase 1b/2 study will be 5 mg/kg, with 
the dose calculated using AIBW, which is one dose level lower than the RP2D (6 mg/kg using 
AIBW) defined in the FIH Study 0401. The expected exposure of patients treated at this dose 
level is within the range of exposure observed in patients with objective responses. Analysis of 
safety, tolerability, PK, and preliminary anti-tumor activity data will help guide future 
development of mirvetuximab soravtansine. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
40 
1.8.2. 
Pembrolizumab 
The dose of pembrolizumab planned for this trial is 200 mg Q3W. The dose recently approved in 
the United States and several other countries for treatment of patients with melanoma is 2 mg/kg 
Q3W. Information on the rationale for selecting 200 mg Q3W is summarized below. 
KEYNOTE-001 is an open-label Phase 1 study conducted to evaluate the safety, tolerability, PK 
and pharmacodynamics, and anti-tumor activity of pembrolizumab when administered as 
monotherapy. The dose escalation portion of this trial evaluated three dose levels, 1 mg/kg, 
3 mg/kg, and 10 mg/kg, administered every 2 weeks (Q2W), and dose expansion cohorts 
evaluated 2 mg/kg administered Q3W and 10 mg/kg Q3W in patients with advanced solid 
tumors. All dose levels were well tolerated, and no dose-limiting toxicities (DLTs) were 
observed. This FIH study of pembrolizumab showed evidence of target engagement and 
objective evidence of tumor size reduction at all dose levels. No MTD has been identified. In 
addition, two randomized cohort evaluations of patients with melanoma receiving 
pembrolizumab at a dose of 2 mg/kg versus 10 mg/kg Q3W have been completed, and one 
randomized cohort evaluating 10 mg/kg Q3W versus 10 mg/kg Q2W has been completed. The 
clinical efficacy and safety data demonstrate a lack of important differences in efficacy or safety 
profile across doses.  
An integrated body of evidence suggests that 200 mg Q3W is expected to provide similar 
response as 2 mg/kg Q3W, 10 mg/kg Q3W, and 10 mg/kg Q2W. A flat pembrolizumab 
exposure-response relationship for efficacy and safety has been found in subjects with melanoma 
in the range of doses between 2 mg/kg and 10 mg/kg. Exposures for 200 mg Q3W are expected 
to lie within this range and will be close to those obtained with 2 mg/kg Q3W.  
A population PK model, which characterized the influence of body weight and other patient 
covariates on exposure, was developed. The PK profile of pembrolizumab was consistent with 
that of other humanized mAbs, which typically have a low clearance and a limited volume of 
distribution. The distribution of exposures from the 200 mg fixed dose are predicted to 
considerably overlap those obtained with the 2 mg/kg dose and, importantly, will maintain 
individual patient exposures within the exposure range established in melanoma as associated 
with maximal clinical response. Pharmacokinetic properties of pembrolizumab, and specifically 
the weight dependency in clearance and volume of distribution, are consistent with no 
meaningful advantage of weight-based dosing versus fixed dosing.  
In translating to other tumor indications, similarly flat exposure-response relationships for 
efficacy and safety as observed in patients with melanoma can be expected, as the anti-tumor 
effect of pembrolizumab is driven through immune system activation rather than through a direct 
interaction with tumor cells, rendering it independent of the specific tumor type. In addition, 
available PK results in subjects with melanoma, NSCLC, and other tumor types support a lack of 
meaningful difference in PK exposures obtained at tested doses among tumor types. Thus, the 
200 mg Q3W fixed-dose regimen is considered an appropriate fixed dose for other tumor 
indications.  
A fixed-dose regimen will simplify the dosing regimen to be more convenient for physicians and 
to reduce potential for dosing errors. A fixed-dosing scheme will also reduce complexity in the 
logistical chain at treatment facilities and reduce waste. The existing data suggest that 200 mg 
Q3W is the appropriate dose for pembrolizumab. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
41 
1.9. 
Safety Rationale for the Triplet Combination 
Preliminary safety data from the mirvetuximab soravtansine + bevacizumab and the 
mirvetuximab soravtansine + carboplatin combinations exhibit TEAEs consistent with the nature 
and severity of the most common preferred terms listed in the respective reference safety 
information for each drug. The doublet combinations were generally well tolerated, and no new 
safety signals were observed at the highest dose levels explored per protocol.  
As of July 2017, TEAEs occurring in > 20% of patients in the mirvetuximab soravtansine + 
bevacizumab combination (n = 41) included nausea, fatigue, blurred vision, diarrhea, peripheral 
neuropathy, headache, hypertension, vomiting, constipation, myalgia, abdominal pain, and 
decreased appetite; the TEAEs were typically ≤ Grade 2. One patient, who was dosed at the 
highest dose level, reported two Grade 2 DLTs (neutropenia and thrombocytopenia). 
Treatment-emergent AEs occurring in > 20% of patients in the mirvetuximab soravtansine + 
carboplatin combination (n = 18) included nausea, thrombocytopenia, diarrhea, vision blurred, 
neutropenia, fatigue, hypokalemia, vomiting, hypomagnesaemia, neuropathy peripheral, 
decreased appetite, headache, dyspnea, anemia, constipation, myalgia, alanine aminotransferase 
(ALT) increased, AST increased, pneumonitis, and pyrexia. The TEAEs were typically ≤ Grade 
2. One DLT (vasculitis, Grade 3) was recorded in one patient in the highest dose level cohort 
(6 mg/kg mirvetuximab soravtansine + AUC 5 carboplatin). Of the 10 patients dosed at the 
highest dose level, six patients required at least one dose delay of carboplatin for a 
myelosuppression event, and four patients required a dose reduction of carboplatin from AUC5 
to AUC4 within the first six cycles of treatment because of a TEAE. Two of the four TEAEs that 
led to a dose reduction of carboplatin were myelosuppressive (Grade 2 thrombocytopenia and 
neutropenia). 
1.10. 
Rationale for the Study Plan 
This is an open-label, Phase 1b/2, non-randomized combination study of mirvetuximab 
soravtansine in adult patients with advanced EOC, primary peritoneal cancer, or fallopian tube 
cancer. Bevacizumab, carboplatin, and pegylated liposomal doxorubicin were selected as 
combination agents on the basis of nonclinical studies showing that the activity of these agents 
was additive with mirvetuximab soravtansine (Section 1.6.1). Pembrolizumab, an anti–PD-1 
monoclonal antibody (mAb), is approved for the treatment of melanoma, NSCLC, head and neck 
squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite 
instability high solid tumors, and gastric/gastroesophageal junction adenocarcinoma and has 
shown preliminary anti-tumor activity as a single agent in EOC (Varga 2015). 
This study is designed to establish the MTD and determine the RP2D of mirvetuximab 
soravtansine when administered in combination with bevacizumab, carboplatin, pegylated 
liposomal doxorubicin or pembrolizumab; and to evaluate the triplet combination of 
mirvetuximab soravtansine at the RP2D with bevacizumab + carboplatin. All study treatments 
will be administered IV. The safety, tolerability, immunogenicity to mirvetuximab soravtansine, 
and preliminary anti-tumor activity of mirvetuximab soravtansine in combination with 
bevacizumab, carboplatin, pegylated liposomal doxorubicin, pembrolizumab, or bevacizumab + 
carboplatin will be characterized. The PK of mirvetuximab soravtansine will be characterized 
along with bevacizumab, carboplatin, and pegylated liposomal doxorubicin concentrations. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
42 
Concentrations of pembrolizumab may be characterized if warranted because of a safety signal. 
Five dosing Regimens will be evaluated in this study:  
Regimen A: mirvetuximab soravtansine + bevacizumab administered on Day 1 of each 
21-day cycle  
Regimen B: mirvetuximab soravtansine + carboplatin administered on Day 1 of each 21-day 
cycle 
Regimen C: mirvetuximab soravtansine + pegylated liposomal doxorubicin administered on 
Day 1 of each 28-day cycle 
Regimen D: mirvetuximab soravtansine + pembrolizumab administered on Day 1 of each 
21-day cycle 
Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin administered on Day 1 
of each 21-day cycle 
Doublet Dosing (Escalation and Expansion) 
The patient population for the Dose Escalation phase (Regimens A through D) and the triplet 
dose (Regimen E) will include patients with EOC, primary peritoneal cancer, or fallopian tube 
cancer.  
In the Dose Escalation phase, patients will be enrolled in groups of three to six until the MTD is 
defined for each Regimen. To further evaluate the safety of each Regimen (Regimens A 
through D), up to 10 patients will be treated at the MTD. Dose Expansion is planned for 
Regimen A and Regimen D to further evaluate the mirvetuximab soravtansine and bevacizumab 
combination and mirvetuximab soravtansine and pembrolizumab combination, respectively, in 
patients with platinum-resistant, advanced EOC.  
Triplet Dosing 
Triplet dosing (Regimen E) will evaluate the mirvetuximab soravtansine + bevacizumab + 
carboplatin combination in patients with platinum-sensitive, advanced EOC. Regimen E may 
enroll approximately 50 patients, as exploration of alternative doses is required to enroll 
approximately 40 patients to be dosed at the maximum dose level determined to be safe. 
The aims of triplet dosing (Regimen E) are to evaluate safety and tolerability of the combination 
and to assess for early signs of activity. The starting doses used in triplet dosing (Regimen E) 
will be derived from all evaluable data from Regimens A and B. The MTD will be determined 
from the assessment of DLTs during the first treatment cycle. Patients will be enrolled in a 
stepwise manner: Initially, six patients will be dosed at the target triplet dose. If that dose is 
considered tolerable, a further six patients will be dosed, followed by the remaining 28 patients.  
Should the initial six or 12 patients not tolerate the starting dose, either the mirvetuximab 
soravtansine dose or the carboplatin dose will be reduced. The reduced triplet doses will always 
be explored in the same stepwise manner as detailed above. A total of 12 patients (6 + 6 patients) 
will be assessed at a dose before the remaining 28 patients are enrolled. The decision of whether 
to reduce the mirvetuximab soravtansine dose or the carboplatin dose will be made according to 
the DLTs.  
Regimen A Cohorts 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
43 
Regimen A initially included bevacizumab-naïve patients (Cohort 1) and bevacizumab 
pre-treated patients (Cohort 2) in the recurrent EOC, platinum-resistant population. On the basis 
of the preliminary results from Regimen A Cohorts 1 and 2 (O’Malley 2018), a third Cohort 
(Cohort 3) will be added to further evaluate the mirvetuximab soravtansine + bevacizumab 
combination in a defined subset of patients with ovarian cancer. Approximately 60 patients will 
be enrolled. The purpose of Cohort 3 is to further explore and confirm the safety and efficacy of 
the mirvetuximab soravtansine + bevacizumab combination in the recurrent EOC patient 
population, including primary peritoneal and fallopian tube cancers. Cohort 3 will include 
patients with one to three prior therapies who may be either platinum resistant or platinum 
sensitive if, in the opinion of the Investigator, a platinum-free doublet is an appropriate next line 
of therapy. Patients with platinum-sensitive EOC often, but not always, receive a platinum-based 
therapy. Platinum-free regimens are used when patients have had unmanageable toxicity with 
platinum-containing chemotherapy, when the maximum lifetime cisplatin dose has been reached, 
when an allergic reaction to carboplatin is of concern, and/or per patient preference. Patients in 
Regimen A Cohort 3 may or may not have received prior therapy with bevacizumab because the 
MITO B16/MaNGO study has demonstrated benefit of bevacizumab re-treatment in patients 
with ovarian cancer. 
1.10.1. 
Rationale for FRα Expression Levels 
Nonclinical data demonstrate that mirvetuximab soravtansine anti-tumor activity correlates with 
FRα expression: The higher the FRα expression, the greater the anti-tumor activity observed in 
nonclinical models (Investigator Brochure). Consistent with these nonclinical data, preliminary 
analysis of single-agent data across low, medium, and high FRα expression subsets, in the FIH 
mirvetuximab soravtansine study, confirmed that the most significant benefit (PFS and ORR) 
was seen in the medium and high subsets. This has led to restriction of eligibility to the medium 
and high subsets of FRα expression in the Forward I single-agent registration-enabling study for 
mirvetuximab soravtansine. 
The initial hypothesis for Study IMGN853-0402 was that while low FRα expression (≥ 25% to 
< 50% cells with at least 2+ staining by IHC) may not be sufficient for maximal anti-tumor 
activity with mirvetuximab soravtansine monotherapy, it might be sufficient for anti-tumor 
activity when mirvetuximab soravtansine is combined with other anti-cancer agents. This 
hypothesis was based on additive/synergistic anti-tumor activity seen when mirvetuximab 
soravtansine is combined with other anti-cancer agents (Investigator Brochure). Data emerging 
from all four combinations (Regimens A through D) in the Dose Escalation phase of Study 
IMGN853-0402 reveal that, as has been observed with mirvetuximab soravtansine monotherapy, 
the higher the FRα expression, the greater the anti-tumor activity in terms of depth of response 
and duration of tumor shrinkage. While the numbers are small, the consistency of data across all 
combination Regimens in Dose Escalation does not support the initial hypothesis. Therefore, the 
Sponsor revised the eligibility criterion in the Dose Expansion phase of Study IMGN853-0402 
(patients enrolled under Protocol Amendment 4 or later) to include patients with medium or high 
FRα expression (at least 50% of cells with at least 2+ staining by IHC), who are most likely to 
benefit from mirvetuximab soravtansine in combination with bevacizumab, pembrolizumab, or 
bevacizumab in combination with carboplatin (Section 3.1). 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
44 
2. 
TRIAL OBJECTIVES AND ENDPOINTS 
All objectives apply to all dosing Regimens and all Cohorts within a Regimen unless otherwise 
noted. 
2.1. 
Primary Objectives 
2.1.1. 
Dose Escalation (Regimens A Through D) 
• Evaluate the safety and tolerability of mirvetuximab soravtansine when given in 
combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin, or 
pembrolizumab (Regimens A, B, C, and D, respectively) in patients with EOC, 
primary peritoneal cancer, or fallopian tube cancer 
2.1.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) 
• Assess preliminary response-based anti-tumor activity of mirvetuximab soravtansine 
when administered in combination with bevacizumab (Regimen A) or 
pembrolizumab (Regimen D) and in combination with bevacizumab and carboplatin 
(Regimen E) in patients with EOC, primary peritoneal cancer, or fallopian tube 
cancer 
2.2. 
Primary Endpoints 
2.2.1. 
Dose Escalation (Regimens A Through D) 
• Treatment-emergent AEs, laboratory test results, physical examination, 
electrocardiograms (ECGs), and vital signs  
2.2.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) 
• Objective response rate, defined as percentage of patients with confirmed response 
(complete response/remission [CR] + partial response/remission [PR]) as assessed by 
Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Appendix G)  
2.3. 
Secondary Objectives 
• Evaluate the safety and tolerability of mirvetuximab soravtansine when administered 
in combination with bevacizumab or pembrolizumab (Dose Expansion, Regimens A 
and D, respectively) and in combination with bevacizumab and carboplatin 
(Regimen E [Triplet]) in patients with EOC, primary peritoneal cancer, or fallopian 
tube cancer 
• Assess preliminary response-based anti-tumor activity of the combination Regimens 
(Dose Escalation, Regimens A through D) 
• Assess PFS 
• Measure duration of response (DOR): the time from first objective response (CR/PR) 
to the time of progressive disease (PD) among those who have achieved a PR or CR  


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
45 
• Assess Gynecologic Cancer Intergroup (GCIG) CA125 response rate of the 
combination Regimens 
• Characterize PK of mirvetuximab soravtansine when used in combination Regimens 
• Evaluate bevacizumab, carboplatin, and pegylated liposomal doxorubicin 
concentrations when administered in combination with mirvetuximab soravtansine  
• Characterize immunogenicity of mirvetuximab soravtansine  
2.4. 
Secondary Endpoints 
• Treatment-emergent AEs, changes in laboratory test results, physical examination, 
ECGs, and vital signs (Dose Expansion [Regimens A and D] and Regimen E 
[Triplet]) 
• Objective response rate, defined as percentage of patients with confirmed response 
(CR + PR) as assessed by RECIST Version 1.1 (Dose Escalation, Regimens A 
through D) (Appendix G) 
• Progression-free survival, defined as the time from first dose to PD or death, 
whichever occurs first 
• Duration of response, defined as the time from first objective response (CR/PR) to the 
time of PD among those who have achieved a PR or CR  
• Number of patients with GCIG CA125 criteria clinical responses (Appendix H) 
• Mirvetuximab soravtansine PK parameters for intact ADC, total antibody, DM4, and 
S-methyl DM4 include, but are not limited to, Cycle 1 and Cycle 3 maximum plasma 
concentration (Cmax), area under the time-concentration curve (AUC), terminal half-
life (t½), clearance (CL), volume of distribution at steady state (Vss), and time that 
Cmax occurs (tmax) 
• Concentration data of bevacizumab, carboplatin, and pegylated liposomal 
doxorubicin will be measured before and after bevacizumab, carboplatin, and 
pegylated liposomal doxorubicin infusions (Cycle 1 through Cycle 6) 
• Immunogenicity: presence of anti-drug antibodies (ADA) to mirvetuximab 
soravtansine   
2.5. 
Exploratory Objectives  
• Assess any association between FRα expression levels and clinical response 
• Identify or evaluate potential biomarkers in blood and tumor tissue that might predict 
response to each of the four combinations  
• Evaluate pembrolizumab concentrations if warranted by a safety signal (Regimen D 
only) 
• Assess anti-tumor activity of the combination with pembrolizumab per 
immune-related RECIST (irRECIST) (Regimen D only) 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
46 
2.6. 
Exploratory Endpoints  
• Correlation of FRα expression, by IHC (protein), quantitative reverse transcriptase-
polymerase chain reaction (mRNA), or other quantitative methods, to clinical 
endpoints 
• Measure biomarkers in blood and tumor tissue including, but not limited to, 
mutational and genomic alterations of tumor samples; expression and activation of 
oncogenic genes and pathways in tumor samples; expression and polymorphism of 
drug transporters such as multidrug resistance protein-1 (p-glycoprotein [PgP]); the 
genotype of FcγR; expression and of immune-related genes and gene signatures 
(Regimen D only), and infiltration of tumor-related immune cells (Regimen D only) 
• Concentration data for pembrolizumab if warranted by a safety signal (Regimen D 
only)  
• Evaluate efficacy endpoints per irRECIST (Appendix I) (Regimen D only)  
− Progression-free survival, ORR, and DOR per irRECIST are defined as specified 
for the respective endpoints using RECIST Version 1.1 above, except that a 
confirmation assessment of PD (at least 4 weeks after the initial PD assessment) is 
required for subjects who remain on treatment after documented PD per RECIST 
Version 1.1. Subjects who discontinue treatment after documented PD assessment 
per RECIST Version 1.1 will be counted as having PD on the date of the 
documented PD assessment.  
Note: Unless specifically warranted by relevance to safety or efficacy endpoints, the exploratory 
endpoints will not be reported in the clinical study report. 
3. 
STUDY POPULATION 
3.1. 
Inclusion Criteria  
3.1.1. 
Inclusion Criteria for All Patients (Dose Escalation and Dose Expansion, 
Regimen-Specific) 
1. Pathologically documented advanced EOC (including primary peritoneal cancer and 
fallopian tube cancer). 
2. Female and ≥ 18 years of age at the time of the first screening visit. 
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. 
4. Measurable disease: 
a. Dose Escalation: Patients may have measurable or non-measurable disease.  
b. Dose Expansion (Regimens A and D) and Regimen E (Triplet): Patients must have at 
least one lesion that meets the definition of measurable disease according to RECIST 
Version 1.1. 
5. Willing to provide an archival tumor tissue block or slides, or a new biopsy if archival 
tumor tissue is unavailable. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
47 
a. Regimen D only: Patients must be willing to undergo two tumor biopsy collections 
using a non-significant risk procedure (see Section 2.1.1). The first biopsy will be 
taken before the first dose of study treatment and the second, taken on Cycle 2 Day 8 
(± 3 days).  
6. Confirmation of FRα positivity by IHC. If the archival tumor tissue does not meet FRα 
criteria, a new tumor biopsy may be submitted and used to meet this criterion. FRα 
expression levels must meet the following criteria: 
a. Dose Escalation (Regimens A through D): ≥ 25% of tumor staining at ≥ 2+ intensity 
b. Dose Expansion (Regimens A and D) and Regimen E (Triplet): ≥ 50% of tumor 
staining at ≥ 2+ intensity 
7. Time from prior therapy: 
a. Systemic anti-neoplastic therapy: five half-lives or 4 weeks, whichever is shorter. 
Hormonal therapy is not considered anti-neoplastic therapy. 
b. Radiotherapy: wide-field radiotherapy (eg, > 30% of marrow-bearing bones) 
completed at least 4 weeks, or focal radiation completed at least 2 weeks, before 
starting study treatment. 
8. Recovered or stabilized to National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) ≤ Grade 2 from all therapy-related toxicities 
(Regimens A through C and Regimen E). 
9. Resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less 
(except alopecia). If patient received major surgery or radiation therapy of > 30 Gy, they 
must have recovered from the toxicity and/or complications from the intervention 
(Regimen D only). 
10. Platinum sensitivity: 
a. Dose Escalation and Dose Expansion: Regimens A (Cohorts 1 and 2) and D and Dose 
Escalation Regimen C: Patients must have disease that is resistant to platinum 
therapy. Platinum-resistant disease is defined as disease that responded to primary 
platinum therapy and then progressed within 6 months (182 days) after the date of the 
last dose of platinum therapy, or disease that progressed during or within 6 months 
(182 days) after the date of the last dose of the subsequent platinum therapy. 
b. Dose Escalation, Regimen B: Patients must have platinum-sensitive disease. 
Platinum-sensitive disease is disease that responded to the last platinum therapy 
received before study entry and did not progress within 6 months (182 days) after the 
date of the last dose of platinum therapy. 
c. Regimen E (Triplet): Patients must have platinum-sensitive disease. Platinum-
sensitive disease is disease that responded to the last platinum therapy received before 
study entry and did not progress within 6 months (182 days) after the date of the last 
dose of platinum therapy. The requirements to demonstrate platinum sensitivity 
(responsiveness and time to progression) apply to each of the patient’s prior platinum-
containing regimens.  
d. Dose Expansion: Regimen A, Cohort 3: Patients may have either platinum-resistant 
disease or platinum-sensitive disease, where a non-platinum doublet is an appropriate 
next line of therapy. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
48 
11. Number of prior therapies (where adjuvant ± neoadjuvant will be considered one regimen 
and maintenance therapy will be considered to be part of the preceding regimen; 
hormonal therapy counts as a separate line of therapy unless given as maintenance): 
a. Dose Escalation (Regimens A through D): There is no upper limit to the number of 
prior treatment regimens received. 
b. Dose Expansion Regimen A, Cohort 1: Patients must have received ≤ two prior 
systemic treatment regimens. 
c. Dose Expansion Regimen A, Cohort 2: Patients must have received at least one but 
not more than five prior systemic treatment regimens. At least one of the prior 
systemic treatment regimens must have included bevacizumab. 
d. Dose Expansion Regimen A, Cohort 3: Patients must have received at least one but 
no more than three prior systemic treatment regimens, where prior regimens may 
have included bevacizumab. 
e. Dose Expansion Regimen D: Patients must have received at least two but not more 
than four prior systemic treatment regimens. 
f. Regimen E (Triplet): Patients must have received at least one but not more than two 
prior systemic treatment regimens; prior systemic treatment regimens may have 
included vascular endothelial growth factor inhibitors (including bevacizumab) and 
must have included at least one platinum-based chemotherapy. 
12. Prior folate receptor–targeting investigational agents treatment: 
a. Dose Escalation (Regimens A through C): Prior treatment with folate receptor–
targeting investigational agents, including mirvetuximab soravtansine (provided it 
was not discontinued because of AEs), is allowed.  
b. Dose Escalation (Regimen D), Dose Expansion (Regimens A and D), and Regimen E 
(Triplet): Patients who have received prior mirvetuximab soravtansine are excluded.  
13. Major surgery (not including placement of vascular access device or tumor punch/scrape 
biopsies) must be completed 4 weeks before Day 1. Patients must have recovered or 
stabilized from the side effects before study treatment. 
14. Adequate hematologic, kidney, and liver function as defined by the following parameters: 
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1,500/μL). 
b. Platelet count ≥ 100 × 109/L (100,000/μL); must not be transfused within previous 
10 days. 
c. Hemoglobin ≥ 9.0 g/dL. 
d. Serum creatinine ≤ 1.5 times the upper limit of the normal range (ULN) or 24-hour 
creatinine clearance of ≥ 60 mL/minute. 
e. AST ≤ 2.5 times the ULN; ALT ≤ 2.5 times the ULN. 
f. Serum bilirubin ≤ 1.5 times the ULN (patients with documented diagnosis of Gilbert 
syndrome are eligible if total bilirubin is < 3.0 times the ULN). 
g. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the ULN 
unless patient is receiving anticoagulant therapy, as long as PT or partial 
thromboplastin time (PTT) is within therapeutic range of intended use of 
anticoagulants. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
49 
h. Activated partial thromboplastin time (aPTT) ≤ 1.5 times the ULN unless patient is 
receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of 
intended use of anticoagulants. 
i. Dose Escalation and Dose Expansion (Regimen D): thyroid-stimulating hormone 
(TSH) within normal limits (WNL). If TSH is not WNL, the patient is eligible if total 
triiodothyronine (T3) or free T3 and free thyroxine (T4) are WNL.  
15. Willing and able to sign the informed consent form (ICF) and to adhere to the study visit 
schedule and other protocol requirements. 
16. Woman of childbearing potential (WCBP), defined as a sexually mature woman who has 
not undergone surgical sterilization or who has not been naturally postmenopausal for at 
least 12 consecutive months (ie, who has had menses any time in the preceding 
12 consecutive months) must agree to use effective contraceptive methods. Acceptable 
single methods include intrauterine device, vasectomy of a female patient’s male partner, 
and contraceptive rod implanted into the skin. Abstinence (relative to heterosexual 
activity) can be used as the sole method of contraception if it is consistently employed as 
the patient’s preferred and usual lifestyle and if considered acceptable by local regulatory 
agencies and independent ethics committees (IECs)/institutional review boards (IRBs). 
Periodic abstinence (eg, calendar, ovulation, sympto-thermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception. Acceptable combination 
methods (requiring use of two of the following) are acceptable: diaphragm with 
spermicide (cannot be used in conjunction with cervical cap/spermicide); cervical cap 
with spermicide (nulliparous women only); contraceptive sponge (nulliparous women 
only); male condom or female condom (cannot be used together); hormonal contraceptive 
such as oral contraceptive pill, estrogen/progestin pill, or progestin-only pill; 
contraceptive skin patch; vaginal contraceptive ring; or subcutaneous contraceptive 
injection. Acceptable methods of contraception must be used while on study treatment 
and for at least 12 weeks after the last dose of mirvetuximab soravtansine; for at least 
6 months after the last dose of bevacizumab, carboplatin, or pegylated liposomal 
doxorubicin; and for at least 4 months after the last dose of pembrolizumab. 
17. WCBP must have a negative pregnancy test within 3 days before the first dose of study 
treatment. 
3.1.2. 
Exclusion Criteria  
1. Male patients. 
2. Primary platinum-refractory disease. Platinum refractory is defined as disease that has not 
responded to a primary platinum-based regimen or progressed within 30 days after 
primary platinum-based therapy. 
3. Clear-cell, mucinous histology, mixed histology with mucinous component, sarcoma, 
sarcomatous component, or low-grade ovarian cancer. 
4. Active or chronic corneal disorders, including but not limited to the following: Sjogren 
syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal 
transplantation, active herpetic keratitis, monocular vision, and/or other active ocular 
conditions requiring ongoing treatment/monitoring, such as wet age-related macular 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
50 
degeneration requiring intravitreal injections, active diabetic retinopathy with macular 
edema, and/or presence of papilledema. 
5. > Grade 1 peripheral neuropathy.  
6. Serious concurrent illness or clinically relevant active infection (testing not required), 
including but not limited to the following: 
a. Known active hepatitis B or C  
b. Known HIV infection 
c. Varicella-zoster virus (shingles)  
d. Cytomegalovirus infection  
e. Any other known concurrent infectious disease requiring IV antibiotics within 
2 weeks before study enrollment 
7. Clinically significant cardiac disease including any one of the following: 
a. Recent myocardial infarction (≤ 6 months before Day 1) 
b. Unstable angina pectoris 
c. Uncontrolled congestive heart failure (New York Heart Association > Class II)  
d. Uncontrolled hypertension (≥ CTCAE Version 4.03 Grade 3) 
e. History of hypertensive crisis or hypertensive encephalopathy 
f. Uncontrolled cardiac arrhythmias 
g. Clinically significant vascular disease (eg, aortic aneurysm or dissecting aneurysm) 
h. Severe aortic stenosis 
i. Clinically significant peripheral vascular disease 
j. ≥ Grade 3 cardiac toxicity following prior chemotherapy 
k. Heart rate–corrected QT interval > 470 msec on the screening ECG 
8. History of multiple sclerosis or other demyelinating disease and/or Eaton-Lambert 
syndrome (para-neoplastic syndrome).  
9. History of hemorrhagic or ischemic stroke within the last 6 months.  
10. History of cirrhotic liver disease. 
11. History of non-infectious interstitial lung disease, including non-infectious pneumonitis 
that required steroids or current pneumonitis.  
12. Prior hypersensitivity to monoclonal antibodies and/or severe hypersensitivity (≥ Grade 
3) to pembrolizumab and/or any of its excipients. 
13. Women who are pregnant or lactating or expecting to conceive children within the 
projected duration of the trial, starting with the screening visit through 6 months after the 
last dose of study treatment (Regimens A, B, and C only). 
14. Carcinomatous meningitis, untreated central nervous system (CNS) disease, or 
symptomatic CNS metastasis. Patients with previously treated CNS metastasis (excluding 
carcinomatous meningitis) may participate if their disease is stable (without evidence of 
progression by imaging, using identical imaging modality at each assessment, for at least 
4 weeks before the first dose of study treatment), have no evidence of new or emerging 
CNS metastasis, and are not using steroids for at least 7 days before the first dose of 
study treatment. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
51 
15. History or evidence of thrombotic or hemorrhagic disorders within 6 months before the 
first dose of study treatment. 
16. Required used of folate-containing supplements (eg, folate deficiency). 
17. Known additional malignancy that is progressing or required active treatment within 
3 years before the first dose of study treatment, excluding adjuvant hormonal therapy for 
breast cancer that was completed. Other exceptions include basal cell carcinoma of the 
skin, squamous cell carcinoma of the skin that has undergone potentially curative 
therapy, and other in situ cancers.  
3.1.2.1. 
Additional Exclusion Criteria for Regimen A and Regimen E 
18. History of bowel obstruction (including sub-occlusive disease) related to underlying 
disease within 6 months before the start of study treatment. 
19. History of abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal 
abscess, or evidence of rectosigmoid involvement by pelvic examination, bowel 
involvement on computed tomography (CT) scan, or clinical symptoms of bowel 
obstruction.  
20. Prior radiotherapy to the pelvis or abdomen (Dose Escalation phase only). 
21. Surgery (including open biopsy) within 4 weeks before starting study therapy (within 
24 hours for minor surgical procedures) or anticipated need for major surgery during 
study treatment. 
22. Non-healing wound, ulcer, or bone fracture.  
23. Hemoptysis ≥ 0.5 teaspoon of red blood within 4 weeks before first study treatment. 
24. History of posterior reversible encephalopathy syndrome (PRES). 
25. Clinically significant proteinuria: urine-protein (UPC) ratio ≥ 1.0 or urine dipstick result 
≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine 
collection and must show result ≤ 1 gram of protein in 24-hour period. 
26. History of pulmonary embolization. 
27. History of Grade 4 thromboembolic events. 
3.1.2.2. 
Additional Exclusion Criteria for Regimen C 
28. Prior treatment with pegylated liposomal doxorubicin and/or doxorubicin. 
29. Left ventricular ejection fraction defined by multigated acquisition (MUGA) 
scan/echocardiogram (ECHO) that is below the institutional lower limit of normal. 
3.1.2.3. 
Additional Exclusion Criteria for Regimen D 
30. Received a live vaccine within 30 days before study enrollment. Seasonal flu vaccines 
that do not contain live virus are permitted. 
31. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other 
form of immunosuppressive therapy within 7 days before the first dose of study 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
52 
treatment. The use of physiologic doses of corticosteroids may be approved after 
consultation with the Sponsor. 
32. Active autoimmune disease that has required systemic treatment in the past 2 years 
(ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). 
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement 
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic 
treatment. 
33. Prior anti-cancer mAb within 4 weeks before study Day 1 or has not recovered 
(ie, ≤ Grade 1 at baseline) from AEs due to agents administered more than 4 weeks 
earlier. 
34. Received transfusion of blood products (including platelets or red blood cells) or 
administration of colony-stimulating factors (including granulocyte colony-stimulating 
factor, granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) 
within 4 weeks before study Day 1. 
35. Known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the trial. 
36. Pregnant or breastfeeding or expecting to conceive children within the projected duration 
of the trial, starting with the screening visit through 120 days after the last dose of study 
treatment. 
37. Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Study Design 
4.1.1. 
Overview and Schema 
This is an open-label, Phase 1b/2, non-randomized combination study of mirvetuximab 
soravtansine with bevacizumab, carboplatin, pegylated liposomal doxorubicin, pembrolizumab, 
or bevacizumab + carboplatin in adult patients with FRα-positive advanced EOC, primary 
peritoneal cancer, or fallopian tube cancer.  
This Phase 1b/2 study comprises a Dose Escalation phase followed by an MTD Expansion phase 
to further characterize the safety profile and confirm the MTD as the RP2D. A triplet Regimen 
(Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin) will be opened to 
evaluate the safety and tolerability and to assess any early signs of activity in patients dosed with 
the combination Regimen (Figure 1).  
The Dose Escalation phase will follow a standard 3 + 3 cohort design. The MTD will be 
determined from the assessment of DLTs during the first treatment cycle (Table 5). A Dose 
Expansion phase is planned for Regimen A (mirvetuximab soravtansine + bevacizumab) and 
Regimen D (mirvetuximab soravtansine + pembrolizumab) and will open pending Sponsor 
decision; patients enrolled in the Dose Expansion phase will receive study treatment at the MTD 
or RP2D determined during Dose Escalation (Figure 1). For Regimen A, patients in the Dose 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
53 
Expansion phase may be enrolled according to prior exposure to bevacizumab into three Dose 
Expansion Cohorts as follows: 1) Dose Expansion Cohort 1: bevacizumab naïve; 2) Dose 
Expansion Cohort 2: bevacizumab pretreated; and 3) Dose Expansion Cohort 3: one to three 
prior treatments, one of which could have been bevacizumab (Figure 1).  
Regimen E (triplet dose) will be opened because enrollment and safety from Regimens A and B 
have been established, and Regimen A (Dose Expansion Cohorts) enrollment is currently 
ongoing. The planned doses for patients receiving the triplet dose (Regimen E) were derived 
from all available data in Regimens A and B. Regimen E may enroll approximately 50 patients, 
as exploration of alternative doses is required to enroll approximately 40 patients, with a plan to 
be dosed at the maximum dose level determined to be safe. 
Safety and tolerability will be assessed on an ongoing basis, and patients will be enrolled initially 
in a stepwise manner.  
The period of observation extends from the time the patient receives the first dose of study 
treatment (mirvetuximab soravtansine and/or combination agent) until the final follow-up study 
visit. Patients will continue to receive mirvetuximab soravtansine and/or the combination agent 
until PD, unacceptable toxicity, or withdrawal of consent, whichever comes first, or until the 
Sponsor terminates the study. Patients who experience PD, as defined by RECIST, while on 
study may remain on study, provided there is evidence of clinical benefit and no unacceptable 
toxicity, as agreed upon by the Investigator and the Medical Monitor. Pembrolizumab 
(Regimen D) will be continued for up to 2 years. Patients who discontinue study treatment for 
reasons other than PD will be followed until PD, start of new anti-cancer therapy, or death, 
whichever occurs first.  
Figure 1: Study Design Schema 
 
a Enrolled 46 patients to ensure 35 patients with tumors expressing FRα at ≥ 50% of tumor staining at intensity ≥ 2+ 
and 11 patients with a FRα 25%-49% of tumor staining at intensity ≥ 2+. 
b Enroll approximately 50 patients to evaluate 40 patients at the MTD. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
54 
4.1.2. 
Cohort Review Committee 
The Cohort Review Committee (CRC) comprises the ImmunoGen Medical Monitor and 
Investigators from participating sites. Once the last patient planned for safety evaluation in a 
given Regimen has completed a cycle of study treatment, a CRC meeting will be convened to 
review all safety data and decide whether to continue or halt Dose Escalation, further expand 
individual dose levels to gain additional safety data, or explore lower or intermediate dose levels. 
In addition to meetings to review safety data at the end of each dose level, the CRC will convene 
to review safety data for ongoing patients and patients in follow-up, per the cohort management 
plan. 
4.1.3. 
Dose Escalation Guidelines 
4.1.3.1. 
Dose Levels and Regimens 
The primary aim of the Dose Escalation phase for each Regimen is to evaluate the safety and 
tolerability of mirvetuximab soravtansine in combination with bevacizumab, carboplatin, 
pegylated liposomal doxorubicin, or pembrolizumab; to identify the MTD and RP2D; and to 
characterize the PK profile of mirvetuximab soravtansine, bevacizumab, carboplatin, and 
pegylated liposomal doxorubicin. The PK profile of pembrolizumab may be characterized if 
warranted because of a safety signal. Patients will be enrolled with 3 to 6 patients until the MTD 
for each of the four Regimens (A through D) is defined. If a patient is eligible for more than one 
combination Regimen, the Investigator will assign the patient to the most appropriate 
combination Regimen, taking into consideration the patient’s disease history, treatment history, 
and/or preferences. Approximately 16 (Regimen A), 22 (Regimen B), 22 (Regimen C), and 
16 (Regimen D) patients will be enrolled in each Regimen, plus an additional 10 patients in each 
arm to define the MTD. 
The starting dose of mirvetuximab soravtansine will be 5 mg/kg, with the dose calculated using 
AIBW. All mirvetuximab soravtansine doses will be calculated according to AIBW. The four 
Regimens (A through D) will be evaluated in parallel and independently.  
The treatment Regimens and planned dose levels for the Dose Escalation phase of the study are 
outlined below and in Table 1, Table 2, Table 3, and Table 4. Enrollment in Regimen A will 
open at the planned dose levels summarized in Table 1.  
Intermediate or lower dose levels of pegylated liposomal doxorubicin, bevacizumab, or 
carboplatin may be explored if DLTs can be attributed to their mechanism of action. Higher 
doses of pegylated liposomal doxorubicin (up to 50 mg/m2) and carboplatin (AUC6) also may be 
considered. 
Table 1: 
Planned Dose Levels (Dose Escalation) for Regimen A (Mirvetuximab Soravtansine 
+ Bevacizumab) 
Dose Level 
Regimen A 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Bevacizumabc 
(mg/kg, D1q3W) 
-1 
4 
15 
1 
5 
15 
2 
6 
15 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
55 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of bevacizumab is 15 mg/kg. 
Table 2: 
Planned Dose Levels (Dose Escalation) for Regimen B (Mirvetuximab Soravtansine 
+ Carboplatin) 
Dose Level 
Regimen B 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Carboplatinc 
(AUC, D1q3W) 
-1 
4 
AUC4 
1 
5 
AUC4 
2 
5 
AUC5 
3 
6 
AUC5 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of carboplatin is AUC6, subject to CRC review. 
Table 3: 
Planned Dose Levels (Dose Escalation) for Regimen C (Mirvetuximab Soravtansine 
+ Pegylated Liposomal Doxorubicin) 
Dose Level 
Regimen C 
Mirvetuximab Soravtansinea 
(mg/kg, D1q4W)b 
Pegylated Liposomal Doxorubicinc 
(mg/m2, D1q4W) 
-1 
4 
30 
1 
5 
30 
2 
5 
40 
3 
6 
40 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 4 weeks. 
c The approved dose of pegylated liposomal doxorubicin for ovarian cancer is 50 mg/m2; however, a decrease in the 
incidence of HFS was observed at a dose of 40 mg/m2 without significant loss in efficacy. Maximum allowable dose is 
50 mg/m2, subject to CRC review. 
Table 4: 
Planned Dose Levels (Dose Escalation) for Regimen D (Mirvetuximab Soravtansine 
+ Pembrolizumab) 
Dose Level 
Regimen D 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Pembrolizumabc 
(mg, D1q3W) 
-1 
4 
200 
1 
5 
200 
2 
6 
200 
a Mirvetuximab soravtansine dose calculated using AIBW. Maximum allowable dose is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of pembrolizumab is 200 mg. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
56 
4.1.3.2. 
Dose Escalation Rules (3 + 3 Design) 
For all patients, Dose Escalation decisions will be made in accordance with a standard 3 + 3 
design. To ensure that those patients consented to a specific Regimen receive study drug in this 
multi-center study, Regimens may be expanded to include additional patients if such patients can 
be treated ≤ 14 days after the third (or sixth) patient was first dosed with mirvetuximab 
soravtansine. In this situation, the decision to dose escalate (or declare the MTD/RP2D) may be 
made after the third evaluable (or sixth evaluable) patient has completed Cycle 1. Intra-patient 
dose escalation will not be permitted. 
• If none of the three or four patients experience a DLT, then dose escalation to the 
next dose level will occur (See Section 4.1.3 for dose levels). 
• If one of the initial three or four patients experiences a DLT, the group will be 
expanded to up to six patients. If no further DLT occurs, dose escalation to the next 
dose level may proceed. 
• If at least two of two to six patients or more than 33% of patients in any given group 
experience a DLT, the maximum administered dose is reached, and no further dose 
escalation will occur. Enrollment into a Regimen at a lower dose level will be 
considered. 
• Each dose level will be evaluated in a similar fashion.  
A patient will be deemed non-evaluable for dose escalation decisions and will not be counted 
toward the total number of evaluable patients in a given dose level if the patient did not receive a 
full course of study treatment (ie, all planned doses of mirvetuximab soravtansine and 
combination drug for first cycle) and did not experience a DLT; or discontinued from the study 
before completing necessary safety evaluations through the end of the first cycle of treatment 
and did not experience a DLT. Non-evaluable patients will be replaced except when accrual to 
the dose level has stopped because of the occurrence of at least two DLTs.  
The MTD is defined as the highest dose at which one or fewer among six patients or ≤ 33% 
experiences a DLT.  
If the maximum planned dose is reached and further dose exploration of pegylated liposomal 
doxorubicin or carboplatin beyond the planned maximum dose of 40 mg/m2 and AUC5, 
respectively, is required to define the MTD, then the CRC will determine the dose escalation 
increments after review of available clinical and PK data. The maximum allowable doses of each 
study drug are as follows: mirvetuximab soravtansine 6.0 mg/kg AIBW every 3 weeks, 
mirvetuximab soravtansine 6.0 mg/kg every 4 weeks, bevacizumab 15 mg/kg every 3 weeks, 
carboplatin AUC6 every 3 weeks, pegylated liposomal doxorubicin 50 mg/m2 every 4 weeks, 
and pembrolizumab 200 mg every 3 weeks. 
If there is evidence of late-occurring or cumulative DLT(s), an ad hoc CRC may be scheduled 
with participating Investigators to discuss dose level or MTD reduction. If agreed, the 
Investigators and Sponsor may increase the number of patients treated at a given dose level, or 
enroll additional patients at the previously completed dose level if doing so is necessary to better 
define the safety of any of the combination Regimens. Additionally, upon review of the safety 
data from the current Cohort, the Sponsor, together with the Investigators, may decide to 
evaluate intermediate dose levels. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
57 
To better characterize safety, 10 patients may be enrolled and treated at the putative MTD. After 
the CRC reviews the safety data from the Dose Escalation phase and agrees that the dose is safe 
to proceed, and the Sponsor approves, the Dose Expansion phase of the trial will commence. 
Dose Expansion is planned for Regimen A and Regimen D; on the basis of emergent data, the 
CRC may decide to expand Regimens B and/or C to collect additional safety information. If 
expanded, Regimens B and C will each enroll a maximum of 20 patients, who will be treated at 
the MTD established for the corresponding Regimen. 
4.1.4. 
Definition of Dose-Limiting Toxicity  
Dose-limiting toxicity will be defined as a TEAE or abnormal laboratory value related to 
mirvetuximab soravtansine and/or the combination drug (ie, assessed as unrelated to disease, 
intercurrent illness, or concomitant medications), including those TEAEs and abnormal 
laboratory values that result in a failure to meet the criteria for re-treatment (Section 5.10.1). 
Dose-limiting toxicities will be considered related to the study treatment unless there is clear 
evidence of an alternative explanation and this attribution is agreed to by the CRC.  
Only DLTs that occur during the first cycle will be considered for decisions regarding dose 
escalation. Clinically significant toxicities or TEAEs that meet the definition of dose limiting but 
occur after Cycle 1 (dose-modifying events) may be considered when determining the MTD.  
If a patient experiences a DLT or an AE that qualifies as a DLT at any point during study 
treatment as outlined in Table 5, the study treatment must be stopped, and the toxicity(ies) in 
question must be followed until resolution or stabilization. If treatment is to be resumed, then 
re-treatment criteria must be met (Section 5.10.3), and administration of mirvetuximab 
soravtansine and/or the combination agent must be resumed at a lower dose per dose the 
modification guidelines (Section 5.10.4). 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
58 
Table 5: 
Dose-Limiting Toxicity Definitions 
Toxicity 
DLT Definition Criteriaa 
Dose delays 
Failure to meet re-treatment criteria within the specified time frame 
(Section 5.10.1) 
Hematology 
• 
CTCAE Grade 4 neutropenia ≥ 7 days 
• 
CTCAE ≥ Grade 3 febrile neutropenia, defined as ANC < 1,000/mm3 
with a single temperature reading of > 38.3°C or sustained 
temperature of ≥ 38°C for > 1 hour 
• 
CTCAE Grade 3 thrombocytopenia, associated with clinically 
significant bleeding that requires transfusion therapy 
• 
CTCAE Grade 4 thrombocytopenia  
Non-hematologic and 
other DLTs 
• 
CTCAE ≥ Grade 3 nausea or vomiting despite the use of optimal 
anti-emetic treatments 
• 
CTCAE ≥ Grade 3 diarrhea despite the use of optimal anti-diarrheal 
treatments 
• 
CTCAE Grade 2 diarrhea lasting > 14 days (Regimen D only) 
• 
CTCAE ≥ Grade 3 ocular AEs 
• 
CTCAE ≥ Grade 3 pneumonitis 
• 
Other non-hematologic toxicities of CTCAE ≥ Grade 3 except for the 
following: 
– AEs related to underlying disease. 
– CTCAE Grade 3 fatigue. 
– Isolated, asymptomatic Grade 3 abnormalities in biochemistry 
laboratory values that last for ≤ 7 days. This includes electrolyte 
abnormalities that respond to medical intervention. 
a An AE meeting criteria is considered a DLT if the event occurred during the first cycle.  
For any dose-limiting hepatic toxicity, evaluations should be performed to determine the underlying etiology and rule 
out drug-induced liver injury (Hy’s Law).  
4.1.5. 
Dose Expansion Phase 
Once the CRC determines the MTD, the CRC will determine the dose and schedule to be 
administered in the Dose Expansion phase. The Dose Expansion phase will begin enrollment 
pending Sponsor decision. The primary aims of the Dose Expansion phase are to further evaluate 
safety and tolerability and to assess preliminary anti-tumor activity of mirvetuximab soravtansine 
in combination with bevacizumab or mirvetuximab soravtansine in combination with 
pembrolizumab. Data obtained in the Dose Expansion phase will help define the RP2D.  
Regimen A (Mirvetuximab Soravtansine + Bevacizumab) 
Patients enrolled in the Dose Expansion phase may be assigned to one of three Dose Expansion 
Cohorts according to previous exposure to bevacizumab as follows:  
1. Dose Expansion Cohort 1: bevacizumab naïve; will enroll approximately 20 patients 
2. Dose Expansion Cohort 2: bevacizumab pretreated; may enroll approximately 35 patients 
3. Dose Expansion Cohort 3: patients with at least one but no more than three prior systemic 
treatment regimens, where prior regimens may have included bevacizumab; may enroll 
approximately 60 patients 
Regimen D (Mirvetuximab Soravtansine + Pembrolizumab) 
The Dose Expansion phase will enroll sufficient patients to ensure that 35 patients are FRα 
≥ 50% of tumor staining at ≥ 2+ intensity. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
59 
Dose Expansion is planned for Regimens A and D, pending Sponsor decision; however, on the 
basis of emerging safety and preliminary anti-tumor activity data, the CRC may make the 
decision to expand Regimens B and/or C to collect additional safety information. If expanded, 
Regimens B and C will each enroll a maximum of 20 patients, who will be treated at the MTD 
established for the corresponding Regimen. 
Safety will be evaluated continuously, separately, and in aggregate in the Dose Expansion 
Cohorts. If at any time ≥ 33% of at least three patients treated in the Dose Expansion Cohort 
experience a Cycle 1 DLT, further enrollment to that Cohort will stop, and the CRC will be 
convened. The CRC will review all available safety data and PK data to determine how further 
dosing should proceed. If it is decided that a new dose should be investigated, enrollment to the 
Cohort will begin anew. 
Regimen E (Triplet Dose: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin) 
Following evaluation of the safety, tolerability, and activity data from patients receiving 
Regimens A (Dose Escalation and Dose Expansion) and B (Dose Escalation) in this study, 
Regimen E (Triplet) will be opened. The planned doses for patients receiving the triplet dose are 
derived from all available data from Regimens A and B. Regimen E may enroll approximately 
50 patients, as exploration of alternative doses is required to enroll approximately 40 planned 
patients to be dosed at the maximum dose level determined to be safe. 
The MTD will be determined from the assessment of DLTs during the first treatment cycle 
(Table 5). 
Initially six patients will be dosed at the target triplet dose (Table 5). If there are < 2 Cycle 1 
DLTs (total), another six patients will be dosed. If there are < 4 Cycle 1 DLTs (total) in all 
12 patients, the remaining 28 patients will be enrolled for a total of approximately 40 planned 
patients. 
If either ≥ 2 DLTs or ≥ 4 DLTs are observed in the first six or 12 patients, respectively, either the 
mirvetuximab soravtansine dose or the carboplatin dose will be reduced. The reduced triplet 
doses will always be explored in the same stepwise manner as detailed above. A total of 
12 patients (6 + 6 patients) will be assessed at a dose before the remaining 28 patients are 
enrolled. The decision of whether to reduce the mirvetuximab soravtansine dose or the 
carboplatin dose will be made according to the DLTs observed, and the new doses will be 
explored as follows: 
a. For DLTs that cannot solely be attributable to mirvetuximab soravtansine, the 
carboplatin dose will be reduced.  
b. For DLTs that are solely attributable to mirvetuximab soravtansine, the mirvetuximab 
soravtansine dose will be reduced.  
If after the doses of carboplatin (a) or mirvetuximab soravtansine (b) are reduced, ≥ 2 DLTs or 
≥ 4 DLTs are observed in the first six or 12 patients, respectively, the dose of the other agent 
(mirvetuximab soravtansine [for a] or carboplatin [for b]) will also be reduced. The triplet dose 
with the reduced mirvetuximab soravtansine and carboplatin doses will then be evaluated. The 
doses to be used in Regimen E are shown in Table 6. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
60 
Table 6: 
Planned Doses for Regimen E 
Dose Level 
Regimen E 
Mirvetuximab 
Soravtansinea 
(mg/kg, D1q3W)b 
Bevacizumab 
(mg/kg, D1q3W) 
Carboplatinc 
(AUC, D1q3W) 
-2 
5 
15 
AUC4 
-1d 
6 
15 
AUC4 
-1e 
5 
15 
AUC5 
1 
6 
15 
AUC5 
a Mirvetuximab soravtansine dose calculated using AIBW. 
b Day 1, every 3 weeks. 
c Carboplatin dose may be reduced to AUC4 if safety data from the first six or 12 patients suggest that the triplet 
dose is not being tolerated. 
d Dose reduction of carboplatin due to carboplatin-associated toxicity. 
e Dose reduction of mirvetuximab soravtansine due to mirvetuximab soravtansine–associated toxicity. 
5. 
STUDY TREATMENT 
5.1. 
Description of Study Treatment 
The investigational study drug, mirvetuximab soravtansine, will be provided by ImmunoGen, 
Inc., at a protein concentration of 5.0 mg/mL in an aqueous pH 5.0 buffered solution.  
Bevacizumab is supplied as a commercially available formulation. Please refer to the 
bevacizumab prescribing information.  
Carboplatin is supplied as a commercially available formulation. Please refer to the carboplatin 
prescribing information.  
Pegylated liposomal doxorubicin is supplied as a commercially available formulation. Please 
refer to the pegylated liposomal doxorubicin prescribing information.  
Pembrolizumab is supplied as a clinical image of the commercially available formulation by 
Merck, and supplied by ImmunoGen. Please refer to the Pharmacy Manual.  
5.2. 
Mirvetuximab Soravtansine Packaging 
Mirvetuximab soravtansine will be provided in a 20 mL Type I glass vial. The container closure 
for the Type I glass vials will consist of a 20-mm, ethylene tetrafluoroethylene–coated serum 
stopper (FluroTec®) on the top and product contact surface, with a 20-mm aluminum TruEdge® 
seal with blue Flip-Off® top. Refer to the Pharmacy Manual for more information. 
5.3. 
Storage, Handling, and Accountability 
Specific details regarding storage and handling can be found in the Pharmacy Manual. 
Please refer to the bevacizumab, carboplatin, pegylated liposomal doxorubicin, and 
pembrolizumab prescribing information regarding the proper storage and handling of these 
compounds. 
Accountability and shipping documents for all drugs supplied by the Sponsor must be 
maintained by the Investigator or designee (eg, the study pharmacist). The Investigator or 
designee must maintain an accurate record of the receipt and dispensing of mirvetuximab 
soravtansine study drugs in a drug accountability log or equivalent. Only participants enrolled in 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
61 
the study may receive study treatment, and only authorized site staff may supply or administer 
treatment. These records must always be available for inspection, and a copy will be supplied to 
ImmunoGen on request. Information recorded on these accountability and shipping documents 
will include quantities received, dates and amount dispensed, the recorder’s initials, patient 
number and initials to whom administered, lot number of drug administered, and drug lost, 
damaged, or destroyed.  
Upon completion of the study, all study drug dispatched to a site must be accounted for and 
unused supplies returned to ImmunoGen or destroyed according to the site’s standard operating 
procedures. The original drug reconciliation records shall be maintained at the site and a copy 
collected and sent to ImmunoGen once a representative of the company has confirmed the drug 
accountability. The pharmacy shall maintain accurate records of all study drugs that have been 
received, stored, dispensed, destroyed, and used. The electronic case report form (eCRF) shall 
also record details of mirvetuximab soravtansine study drug administration, such as date and 
time of administration. 
Drug accountability will be monitored regularly. 
5.4. 
Study Treatment Compliance 
Mirvetuximab soravtansine and combination drugs supplied for the study (if any) may not be 
used for any purpose other than the study or administered other than as described in this 
protocol.  
Mirvetuximab soravtansine from two different drug lots cannot be mixed in a single dose 
administration. 
Under no circumstances is the Investigator allowed to release study drug supplies to any 
physician not named in the US Food and Drug Administration (FDA) Form 1572 or to 
administer these supplies to a patient not enrolled in this study. If investigational supplies are to 
be dispensed from any facility other than that supervised directly by the Investigator (ie, hospital 
pharmacy, satellite pharmacy), it is the responsibility of the Investigator to ensure that all study 
drug is maintained in the manner described. 
5.5. 
Assignment of Patient Number 
Patient numbers are assigned by the site after patients sign the ICF to participate.  
The Investigator will certify that the patient satisfies all eligibility criteria at screening and 
continues to satisfy all inclusion and exclusion criteria on Cycle 1 Day 1 before dosing.  
5.5.1. 
Enrolled Patient Definition 
Patients who have signed an IRB/IEC-approved ICF and who have received at least one dose of 
mirvetuximab soravtansine will be considered enrolled. Patients who are issued a patient number 
but who do not successfully complete the screening process and who do not receive a dose of 
mirvetuximab soravtansine and/or combination drug will be considered screen failures. Patient 
numbers for patients who fail screening will not be re-issued. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
62 
5.5.2. 
Patient Assignment to Dosing Regimens 
Patients will be assigned to Regimen A, B, C, D, or E on the basis of eligibility criteria and slot 
availability as determined by the Sponsor. If a patient is eligible for more than one combination 
Regimen, the Investigator will assign the patient to the most appropriate combination Regimen, 
taking into consideration the patient’s disease history, treatment history, and/or preferences.  
5.6. 
Blinding 
Not applicable; this is an open-label study. 
5.7. 
Study Treatment Administration 
5.7.1. 
Study Treatment Overview and Schedule 
Mirvetuximab soravtansine is an experimental anti-cancer drug, and as with other potentially 
toxic compounds, caution should be exercised when handling this compound. It is recommended 
that gloves and protective garments be worn during preparation. Similar precautions should be 
taken when handling bevacizumab, carboplatin, pegylated liposomal doxorubicin, and 
pembrolizumab. Refer to the Pharmacy Manual, Investigator Brochures, and package inserts for 
more information. 
For logistical reasons such as holidays, delays in the scheduled study treatment of up to 3 days 
will be permitted in Cycles 1 and 2. Additionally, shifts in the start of a new cycle by -1 or 
+3 days will be permitted in Cycles ≥ 3. 
5.8. 
Study Drug Preparation and Administration 
5.8.1. 
Premedication for Study Treatment 
All patients must receive 325 to 650 mg of acetaminophen/paracetamol (per orem [by mouth] 
[PO] or IV), 10 mg IV dexamethasone, and 25 to 50 mg diphenhydramine (PO or IV) (equivalent 
drugs of similar drug classes are also acceptable) approximately 30 minutes before each infusion 
of mirvetuximab soravtansine. If individual patients require more intensive treatment to prevent 
infusion-related reactions, investigators may modify the regimen accordingly. Patients being 
treated with bevacizumab, carboplatin, pegylated liposomal doxorubicin, or pembrolizumab in 
the absence of mirvetuximab soravtansine may receive premedication at the discretion of the 
Investigator or according to institutional guidelines. Patients treated with pembrolizumab in the 
absence of mirvetuximab soravtansine will not receive premedication with steroids. 
5.8.2. 
Prophylactic Use of Corticosteroid Eye Drops 
Patients receiving mirvetuximab soravtansine will be required to use corticosteroid eye drops as 
prescribed by the treating physician unless the risk outweighs the benefit per the 
ophthalmologist/physician. Patients will be instructed to self-administer 1% prednisolone (Pred 
Forte® or generic equivalent) six times daily on Days 1 through 4 and four times daily on Days 5 
through 8 of each cycle during the study (see Appendix O). For individual patients who cannot 
tolerate the preservative contained in 1% prednisolone, other corticosteroid eye drops may be 
substituted (eg, difluprednate 0.05%; Durezol®) and administered on Days 1 through 8 of each 
cycle at a frequency prescribed by the ophthalmologist. Patients should be advised to wait at 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
63 
least 15 minutes after corticosteroid eye drop administration before instilling preservative-free, 
lubricating eye drops.  
5.8.3. 
Lubricating Artificial Tears 
Patients receiving mirvetuximab soravtansine will be required to use preservative-free, 
lubricating artificial tears on a daily basis (as directed by the product label or the treating 
physician). Patients should be advised to wait at least 15 minutes after corticosteroid eye drop 
administration before instilling lubricating eye drops.  
5.8.4. 
Preparation and Administration of Mirvetuximab Soravtansine  
5.8.4.1. 
Calculation for Adjusted Ideal Body Weight  
The AIBW will be used to calculate the dose of mirvetuximab soravtansine in this study 
(Appendix L). 
The total dose of drug will be calculated on the basis of each patient’s AIBW using the following 
formula: 
Adjusted Ideal Body Weight (AIBW) 
IBWa + 0.4 (Actual Weight − IBWa), 
where: 
Ideal Body Weight (IBW) 
IBWa (Male) = 0.9Ha – 88, and 
IBWa (Female) = 0.9Ha – 92. 
a H = height in cm; W = weight in kg. 
The weight used for calculation should be obtained before study drug administration on Cycle 1 
Day 1 (± 14 days) and thereafter should be modified only for significant (≥ 10%) changes in 
body weight (not influenced by weight gain or loss attributed to fluid retention).  
5.8.4.2. 
Preparation of Mirvetuximab Soravtansine  
The desired amount of mirvetuximab soravtansine should be withdrawn from the vial(s) and 
diluted using 5% dextrose to a final concentration as outlined in the Pharmacy Manual. Note: 
mirvetuximab soravtansine is incompatible with saline (0.9% sodium chloride); therefore, 
dilutions must be made using 5% dextrose. Infusion bags must be labeled with the protocol 
number, patient number, storage temperature, dose, and volume of mirvetuximab soravtansine 
filtered into the bag, or according to institutional protocol. Once the solution is prepared, the 
infusion bag must not be left in direct sunlight, and the infusion must be completed within 
8 hours after preparation. 
Study drug from two different drug lots cannot be mixed in a single dose administration. 
5.8.4.3. 
Administration of Mirvetuximab Soravtansine  
The starting dose level of mirvetuximab soravtansine will be 5 mg/kg using AIBW for all 
combinations. Mirvetuximab soravtansine should be administered first, followed by the 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
64 
assigned combination drug (bevacizumab, carboplatin, pegylated liposomal doxorubicin, or 
pembrolizumab) for Regimens A, B, C, and D; for Regimen E, mirvetuximab soravtansine 
should be administered first, followed by bevacizumab and then carboplatin. Mirvetuximab 
soravtansine will be administered as an IV infusion after preparation as outlined in the Pharmacy 
Manual. Details for required and compatible infusion materials are included in the Pharmacy 
Manual. For patients who have not been administered mirvetuximab soravtansine as a prior anti-
cancer therapy, mirvetuximab soravtansine should be administered at a rate of 1 mg/min; after 
30 minutes, the rate can be increased to 3 mg/min if well tolerated. If well tolerated after 
30 minutes at 3 mg/min, the mirvetuximab soravtansine infusion rate may be increased to 
5 mg/min. Subsequent infusions may be delivered at the tolerated rate. For patients who have 
been administered mirvetuximab soravtansine as a prior anti-cancer therapy, mirvetuximab 
soravtansine should be administered at the tolerated rate of prior mirvetuximab soravtansine 
infusions. Therefore, the overall length of infusion will vary depending on dose and patient 
tolerability. After infusion, the IV line should be flushed with 5% dextrose as needed to ensure 
delivery of the full dose.  
Patients will be carefully observed during each infusion and vital signs taken as outlined in the 
Schedule of Clinical Assessments (Appendix A, Appendix B, and Appendix C). Patients will 
remain in the clinic under observation for 4 hours after completing the first infusion of 
mirvetuximab soravtansine, and for at least 1 hour after each subsequent infusion.  
5.8.5. 
Preparation and Administration of Bevacizumab 
Bevacizumab will be prepared per label and administered per protocol. Total body weight at 
Cycle 1 Day 1 (± 14 days) is to be used to calculate the required dose. No dose modifications are 
foreseen unless the patient’s body weight changes by ± 10% from baseline. 
5.8.6. 
Preparation and Administration of Carboplatin 
Carboplatin will be prepared per label and administered per protocol. Carboplatin dosing will be 
calculated using the Calvert formula (Appendix J). The maximum carboplatin dose should not 
exceed AUC (mg × min/mL) × 150 mL/min (Griggs 2012). 
If the patient has a history of allergic reaction when administered carboplatin or other platinum 
agents or experiences an allergic reaction to carboplatin while on study, carboplatin must be 
administered per institutional protocol for carboplatin desensitization. Dosing information will 
be entered on the dosing eCRF. 
5.8.7. 
Preparation and Administration of Pegylated Liposomal Doxorubicin 
Pegylated liposomal doxorubicin will be prepared per label and administered per protocol. Body 
weight at Cycle 1 Day 1 (± 14 days) is to be used to calculate the body surface area 
(Appendix K), which will be used to determine the required pegylated liposomal doxorubicin 
dose. No dose modifications are foreseen unless the patient’s body weight changes by ± 10% 
from baseline.  
5.8.8. 
Preparation and Administration of Pembrolizumab 
Pembrolizumab will be administered at a dose of 200 mg using a 30-minute IV infusion. Sites 
should make every effort to target infusion timing to be as close to 30 minutes as possible. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
65 
However, given the variability of infusion pumps from site to site, a window between -5 minutes 
and +10 minutes is permitted (ie, infusion time is 30 minutes − 5 minutes or + 10 minutes). 
The Pharmacy Manual contains specific instructions for preparing the pembrolizumab infusion 
and administering the infusion solution. 
5.9. 
Monitoring and Management of Adverse Events 
5.9.1. 
Potential Infusion-Related Reactions  
Some patients treated with IV infusions of therapeutic drugs have experienced concurrent 
infusion-related reactions (see CTCAE Version 4.03). The signs and symptoms may vary and 
include, for example, headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, 
dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, lightheadedness, 
hypotension, palpitations, and somnolence. Anaphylaxis might occur at any time during an 
infusion. Before any infusion is started, appropriate medical personnel, medication 
(eg, epinephrine, inhaled beta agonists, antihistamines, and corticosteroids), and other required 
resources to treat anaphylaxis must be readily available. In general, Investigators should manage 
acute allergic or hypersensitivity reactions according to institutional practices. General 
guidelines for the management of acute infusion-related reactions and for subsequent 
re-treatment are provided in Table 7. Delayed infusion-related reactions may occur; therefore, 
patients should be advised to seek immediate medical treatment if symptoms newly develop 
and/or recur after discharge from clinic. 
Patients who experience an infusion-related reaction during or immediately after mirvetuximab 
soravtansine administration should have blood drawn to determine drug concentration and 
antibodies to mirvetuximab soravtansine (ADA), if feasible. The sample should be obtained 
within 3 hours after the onset of the reaction and again 1 week later. These patients should 
undergo all scheduled anti-tumor activity and safety evaluations. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
66 
Table 7: 
Management Guidelines for Potential Infusion-Related Reactions  
Infusion Reaction 
CTCAE Version 4.03 
Severity Grade 
Management 
Grade 1: mild, transient 
reaction 
• 
Maintain infusion rate unless progression of symptoms to ≥ Grade 2; if 
symptoms worsen, refer to guidelines below. 
• 
Promethazine (or equivalent) 150 mg PO per day prn for nausea. 
• 
Diphenhydramine (or equivalent) 25-50 mg PO or IV prn. 
• 
Methylprednisolone 125 mg (or equivalent) IV prn. 
Grade 2: moderate  
• 
Interrupt infusion and disconnect infusion tubing from subject. 
• 
Promethazine (or equivalent) 150 mg PO per day prn for nausea. 
• 
Diphenhydramine (or equivalent) 25-50 mg PO or IV prn. 
• 
Acetaminophen (or equivalent) 650 mg PO prn. 
• 
Methylprednisolone 125 mg (or equivalent) IV prn. 
• 
After recovery from symptoms, resume the infusion at 50% of the 
previous rate, and if no further symptoms appear, gradually increase 
rate until infusion is completed. 
• 
For subsequent dosing in future cycles, patients should be 
premedicated with dexamethasone (or equivalent) 8 mg PO BID the 
day before drug administration, and acetaminophen (or equivalent) 650 
mg PO and diphenhydramine (or equivalent) 25-50 mg PO 30-60 
minutes before dosing.  
Grade 3: severe, 
prolonged reaction not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion; recurrence of 
symptoms following 
initial improvement; 
hospitalization indicated 
for clinical sequelae 
OR 
Grade 4: life-threatening 
consequences, urgent 
intervention indicated 
• 
Immediately stop infusion and disconnect infusion tubing from subject. 
• 
Administer diphenhydramine (25-50 mg) IV (or equivalent). 
• 
Administer IV steroids (methylprednisolone (or equivalent) up to 
0.5 mg/kg every 6 hours) to treat ongoing reaction and prevent 
recurrence. 
• 
Administer bronchodilators (nebulized albuterol/salbutamol, 2.5-5 mg in 
3 mL of saline or equivalent) as medically indicated. 
• 
Administer normal saline as medically indicated.  
• 
Administer epinephrine (0.2-0.5 mL of a 1:1000 dilution (0.2-0.5 mg) SQ 
or IM) as medically indicated. Epinephrine should be used only if all 
other treatment methods fail to manage the infusion-related reaction. 
• 
Advise patient to seek emergency treatment and notify 
investigator/clinic if the infusion-related symptoms recur after discharge 
from clinic. 
• 
Report as an SAE (see Section 9.1.1.2). 
• 
Permanently discontinue study medication treatment. 
BID = twice daily, IM = intramuscular, prn = as needed, SAE = serious adverse event, SQ = subcutaneous. 
5.9.2. 
Monitoring and Management of Treatment-Emergent Ocular Disorders 
5.9.2.1. 
Monitoring of Potential Ocular Disorders 
Changes in visual acuity resulting from corneal epithelium disorders have been reported in other 
studies of DM4-containing immunoconjugates that use the SPDB linker (Younes 2012). Because 
of the observation of ocular disorders in patients treated with mirvetuximab soravtansine Q3W at 
dose levels > 3.3 mg/kg, ocular function will be carefully monitored. Complete ophthalmologic 
exams and ocular symptom assessments will be performed in all patients at baseline and 
post-treatment as described in Table 8. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
67 
Table 8: 
Schedule for Ophthalmic Assessments 
Assessment 
Screening 
Day 1 
(All 
Cycles) 
Before Day 1 
Dose 
(Every Other 
Cycle)a 
30 Day Safety 
Follow-up Visit 
or 
End of 
Treatment Visit 
Ophthalmologic history: Patients will 
be asked about ocular symptoms 
such as history of dry eye and 
contact lens use. 
X 
 
 
 
Complete Examb: 
- 
Visual acuity 
- 
Indirect fundoscopy 
- 
Slit lamp examination under 
dilatation 
- 
Intraocular pressure 
measurement 
- 
Corneal photographyc 
Xd 
 
Patients who 
report treatment-
emergent 
changes in vision 
X 
Schirmer teste 
X 
 
X 
 
Ocular symptom assessment 
(blurred vision, ocular discomfort, 
etc) 
X 
X 
 
X 
a Within 1 week before the Day 1 dose of every other cycle; required for patients who have experienced signs or 
symptoms of ocular toxicity and for those with blurred vision but normal eye exams. 
b Performed by a board-certified ophthalmologist. 
c When feasible, to document corneal abnormalities such as the presence of microcysts or keratitis (not required at 
baseline). 
d Within 14 days before Cycle 1 Day 1. 
e For patients experiencing ocular symptoms, the Schirmer test will be repeated at the first ophthalmology exam and 
in subsequent ophthalmologic exams if clinically indicated. 
If a patient develops > CTCAE Grade 1 ocular symptoms (Appendix M), treatment with 
mirvetuximab soravtansine will be interrupted. Treatment should not be interrupted solely for 
Grade 2 ocular signs (eg, Grade 2 keratopathy) unless they are also associated with Grade 2 
ocular symptoms. The patient will be referred to an ophthalmologist for a complete examination 
including visual acuity, slit lamp examination under dilatation, intraocular pressure assessment, 
and indirect fundoscopy. When feasible, corneal photographs should be obtained to document 
corneal abnormalities such as presence of microcysts or keratitis. Therapy may resume if ocular 
symptoms improve to Grade 1 or baseline within one cycle. After the development of ocular 
AEs, a complete ocular examination will be required at every other cycle going forward (or more 
frequently if clinically indicated) and at either the end of treatment or at the 30-day follow-up 
visit.  
5.9.2.2. 
Management Guidelines for Ocular Disorders 
To prevent dry eye, which may predispose a patient to corneal irritation, patients will be required 
to use preservative-free, lubricating artificial tears on a daily basis (as directed by the product 
label or the treating physician) for the duration of their mirvetuximab soravtansine treatment. 
Patients should also be firmly advised to avoid using contact lenses while on study. Baby 
shampoo and a soft cloth should be used to clean the eyes, and a warm compress at bedtime may 
be used to decrease any possible inflammation on the eyelid’s surface. The use of UVA/UVB 
sunglasses is recommended when outside in full daylight during the course of the study. The use 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
68 
of punctal plugs to increase lubrication of the eyes is also recommended. If patients report signs 
or symptoms of ocular disorders including, but not limited to, blurred vision or eye irritation, the 
management and dose modification guidelines outlined in Table 9 should be followed.  
Patients who have experienced study drug–related changes in vision, such as blurred vision, will 
have a complete ophthalmic examination performed before the start of every other cycle and at 
the end of treatment visit or the 30-day follow-up visit after the end of treatment, even if the 
results of the patient’s ocular exam are normal. Management of treatment-emergent ocular 
disorders with inflammatory characteristics should include corticosteroid eye drops and/or other 
measures as indicated by an ophthalmologist. 
Table 9: 
Management of Ocular Disorders 
Severity Grade 
(CTCAE Version 
4.03 Grade)a 
Management 
Guidelines for Mirvetuximab 
Soravtansine Dose 
Modifications 
Grade 1 
• Complete eye exam as outlined in 
Table 8. 
• Monitor for worsening symptoms. 
• Continue mirvetuximab 
soravtansine dosing. 
Grade 2 symptoms 
• Complete eye exam as outlined in 
Table 8. Repeat complete exam as 
clinically indicated.  
• Patients should have weekly 
symptomatic ocular assessments until 
the symptoms resolve to Grade 1 or 
baseline (Section 5.10.1) or are deemed 
irreversible by the Investigator. 
• Resume therapy when ocular symptoms 
improve to Grade 1 or baseline. 
• Hold mirvetuximab 
soravtansine dosing.  
• Patients with ocular disorders 
lasting fewer than 14 days 
may be allowed to resume 
therapy at the same dose 
level.  
• Patients with ocular disorders 
who experience dosing 
delays > 14 days may 
resume treatment at a 
reduced dose level (see 
Table 15).  
Grade 3 
• Complete eye exam as outlined in 
Table 8. Repeat complete exam as 
clinically indicated. 
• Patients should have weekly 
symptomatic ocular assessments until 
the symptoms resolve to Grade 1 or 
baseline (Section 5.10.1) or are deemed 
irreversible by the Investigator. 
• Resume therapy when ocular symptoms 
improve to Grade 1 or baseline. 
• Hold mirvetuximab 
soravtansine dosing.  
• Patients may be allowed to 
resume therapy at a lower 
dose than the one they were 
receiving when their 
symptoms began (see 
Table 15). 
Grade 4 
• Complete eye exam as outlined in 
Table 8. Repeat complete exam as 
clinically indicated. 
• Patients should have weekly 
symptomatic ocular assessments until 
the symptoms resolve to Grade 1 or 
baseline (Section 5.10.1) or are deemed 
irreversible by the investigator. 
• Permanently discontinue 
mirvetuximab soravtansine 
dosing. 
a Appendix M includes CTCAE Version 4.03 grade definitions for select ocular disorders. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
69 
5.9.3. 
Monitoring of Non-infectious Pneumonitis After Administration of Study 
Treatment 
Non-infectious pneumonitis has been observed after administration of mirvetuximab 
soravtansine and may result in fatigue, shortness of breath, cough, or respiratory distress. 
Drug-induced pneumonitis may be immediately life-threatening. If a patient presents with signs 
or symptoms consistent with pneumonitis and/or a clinically meaningful change in pulse 
oximetry value, the patient should be immediately evaluated. Patients are advised to notify their 
treating physician immediately if they experience new or worsening shortness of breath, cough, 
or respiratory distress. 
For patients diagnosed with pneumonitis without an infectious etiology, the management and 
treatment guidelines outlined in Table 10 should be followed. 
Table 10: 
Management of Non-infectious Pneumonitis 
Severity Grade 
(CTCAE Version 
4.03 Grade)  
Medical Management of Pneumonitis 
Guidelines for Dose 
Modifications 
Grade 1 
• Radiologic assessments (CT scan and/or chest 
x-ray) should be performed as clinically 
indicated. 
• Monitor for pulmonary symptoms. 
• Continue dosing after 
discussion with the 
Sponsor. 
Grade 2 
• Radiologic assessments (CT scan and/or chest 
x-ray) should be performed as clinically 
indicated. 
• Patient must be evaluated by a pulmonary 
specialist. 
• Treatment with corticosteroids may be indicated 
as recommended by a pulmonary specialist 
and/or institutional guidelines (Regimens A, B, 
C, and E only). 
• Treat with systemic corticosteroids. When 
symptoms improve to Grade 1 or less, steroid 
taper should be started and continued over no 
fewer than 4 weeks (Regimen D only). 
• Hold dosing of 
mirvetuximab 
soravtansine until 
symptoms resolve to 
Grade 1 or better.  
• Hold dosing of 
pembrolizumab until 
symptoms resolve to 
Grade 1 or better 
(Regimen D only). 
• Mirvetuximab 
soravtansine may be 
resumed at same dose 
level after discussion 
with the Sponsor. 
• Pembrolizumab may be 
resumed at same dose 
level after discussion 
with the Sponsor. 
• Discontinue 
mirvetuximab 
soravtansine and 
pembrolizumab if 
recurrent Grade 2 
pneumonitis occurs 
upon re-challenging. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
70 
Table 10: 
Management of Non-infectious Pneumonitis (Continued) 
Severity Grade 
(CTCAE Version 
4.03 Grade)  
Medical Management of Pneumonitis 
Guidelines for Dose 
Modifications 
Grade 3 
• Radiologic assessments (CT scan and/or chest 
x-ray) should be performed as clinically 
indicated. 
• Patient must be evaluated by a pulmonary 
specialist. 
• Treatment with corticosteroids until resolution of 
symptoms may be indicated as recommended 
by a pulmonary specialist and/or institutional 
guidelines (Regimens A, B, C, and E only). 
• Immediately treat with IV steroids. Administer 
additional anti-inflammatory measures as 
needed (Regimen D only). 
• Add prophylactic antibiotics for opportunistic 
infections in the case of prolonged steroid 
administration (Regimen D only). 
• Bronchoscopy with lavage and/or biopsy should 
be performed when clinically feasible. 
• The pneumonitis event must be followed until 
resolution.  
• Permanently discontinue 
mirvetuximab 
soravtansine.  
• Permanently discontinue 
pembrolizumab 
(Regimen D only). 
Grade 4 
• Radiologic assessments (CT scan and/or chest 
x-ray) should be performed as clinically 
indicated. 
• Patient must be evaluated by a pulmonary 
specialist. 
• Treatment with corticosteroids until resolution of 
symptoms may be indicated as recommended 
by a pulmonary specialist and/or institutional 
guidelines (Regimens A, B, and E only). 
• Immediately treat with IV steroids. Administer 
additional anti-inflammatory measures as 
needed (Regimen D only). 
• Add prophylactic antibiotics for opportunistic 
infections in the case of prolonged steroid 
administration (Regimen D only). 
• Bronchoscopy with lavage and/or biopsy should 
be performed when clinically feasible. 
• The pneumonitis event must be followed until 
resolution. 
• Permanently discontinue 
mirvetuximab 
soravtansine dosing. 
• Permanently discontinue 
pembrolizumab 
(Regimen D only). 
a Appendix M includes CTCAE Version 4.03 grade definitions for pneumonitis. 
5.9.4. 
Monitoring and Management of Diarrhea After Administration of Study 
Treatment 
5.9.4.1. 
Mirvetuximab Soravtansine–Associated Diarrhea  
Mild to moderate diarrhea has been frequently reported in patients treated with mirvetuximab 
soravtansine. Patients should be advised to contact their treating physician at the first sign of 
diarrhea. Patients may then be treated according to standard institutional practice. One 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
71 
suggested regimen is 2 mg loperamide at the first sign of loose stool, with repeat dosing every 
2 hours until symptoms resolve (Wadler 1998). 
5.9.4.2. 
Pembrolizumab-Associated Diarrhea and/or Colitis  
Patients should be carefully monitored for signs and symptoms of enterocolitis (such as diarrhea, 
abdominal pain, blood or mucus in stool, with or without fever) and of bowel perforation (such 
as peritoneal signs and ileus).  
All patients who experience diarrhea/colitis should be advised to drink liberal quantities of clear 
fluids. If sufficient oral fluid intake is not feasible, fluid and electrolytes should be substituted 
via IV infusion. For Grade 2 or higher diarrhea, consider GI consultation and endoscopy to 
confirm or rule out colitis. 
• For Grade 2 diarrhea/colitis, administer oral corticosteroids.  
• For Grade 3 or 4 diarrhea/colitis, treat with IV steroids followed by high-dose oral 
steroids.  
When symptoms improve to Grade 1 or less, steroid taper should be started and continued over 
no fewer than 4 weeks. 
Refer to Table 21 for dose modifications and discontinuation of pembrolizumab. 
5.9.4.3. 
Diarrhea Associated With Mirvetuximab Soravtansine and Pembrolizumab 
Management guidelines for pembrolizumab-associated diarrhea should be followed 
(Section 5.9.4.2). 
5.9.5. 
Monitoring and Management of Nausea and Vomiting After Administration of 
Study Treatment 
Nausea and vomiting have been reported in patients treated with mirvetuximab soravtansine 
and with carboplatin. Patients should be advised to contact their treating physician at the first 
sign of vomiting or worsening nausea. Patients should be treated according to the American 
Society of Clinical Oncology (ASCO) Clinical Practice Guidelines for the use of anti-emetics 
(Basch 2011) outlined in Table 11. 
Table 11: 
Management of Nausea and Vomiting 
Severity Grade 
(CTCAE Version 
4.03 Grade) 
Management 
Grade 1 
• No additional therapy is required. 
Grade 2 
• Administer a 5-HT3 receptor antagonist on Day 1 (eg, palonosetron, 
granisetron, or ondansetron) in combination with dexamethasone on Days 1-3 
or treat per institutional guidelines. Aprepitant may be added to the 
combination. 
Grades 3 and 4 
• Administer a neurokinin 1 receptor antagonist (eg, aprepitant on Days 1-3 or 
fosaprepitant on Day 1) in combination with a 5-HT3 receptor antagonist on 
Day 1 only, and dexamethasone on Days 1-3 or 1-4, or treat per institutional 
guidelines. 
5-HT3 = 5-hydroxytryptamine type 3. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
72 
5.9.6. 
Monitoring of Bevacizumab-Associated Posterior Reversible Encephalopathy 
Syndrome  
There have been rare reports of patients treated with bevacizumab who develop signs and 
symptoms consistent with the neurological disorder PRES. Signs and symptoms of PRES 
include seizures, headache, confusion, and visual disturbance or cortical blindness, with or 
without associated hypertension. Magnetic resonance imaging (MRI) of the brain will confirm 
the diagnosis of PRES. Bevacizumab treatment should be discontinued in patients who develop 
signs and/or symptoms consistent with PRES, and the specific symptoms should be appropriately 
treated. 
5.9.7. 
Monitoring and Management of Bevacizumab-Associated Hypertension 
Patients receiving bevacizumab must be closely monitored for the development of new or 
worsening hypertension. Blood pressure measurements should be performed after the patient has 
been in a resting position for ≥ 5 minutes. If the initial blood pressure reading is ≥ 140 mm Hg 
systolic and/or ≥ 90 mm Hg diastolic, the result should be verified with a repeat measurement. If 
bevacizumab treatment-related hypertension develops, it should be managed as described in 
Table 12. 
Table 12: 
Management of Hypertension After Bevacizumab Administration 
Severity Grade 
(CTCAE Version 
4.03 Grade) 
Hypertension Pattern 
Bevacizumab Dose Modifications 
Grade 1 
Asymptomatic, transient (< 24 h) BP 
increase by > 20 mm Hg (diastolic) or to 
> 150/100 mm Hg if previously within 
normal limits. 
Continue bevacizumab. 
Grade 2 
Recurrent or persistent (> 24 h) or 
symptomatic increase by > 20 mm Hg 
(diastolic) or to > 150/100 mm Hg if 
previously within normal limits. 
Withhold bevacizumab. Start anti-
hypertensive therapy. Once BP is 
< 150/100 mm Hg, patients may continue 
bevacizumab therapy. 
Grade 3 
Requires more than one anti- hypertensive 
drug or more intensive therapy than 
previously. 
Hold bevacizumab for persistent or 
symptomatic hypertension and discontinue 
permanently if hypertension is not 
controlled according to Investigator 
judgment. 
Grade 4 
Life-threatening consequences (eg, 
hypertensive crisis). 
Permanently discontinue bevacizumab. 
BP = blood pressure. 
5.9.8. 
Monitoring and Management of Bevacizumab-Associated Proteinuria 
Proteinuria will be assessed within 48 hours before each bevacizumab treatment by urine 
dipstick analysis method, UPC, 24-hour urine collection, or according to local institutional 
guidelines. Proteinuria should be managed according to Table 13.  
Table 13: 
Management of Bevacizumab-Associated Proteinuria 
CTCAE Grade  
Bevacizumab Dose Modifications 
< 3 
No bevacizumab dose modifications 
3 
Hold bevacizumab.  


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
73 
Nephrotic syndrome (CTCAE 
Grade 4) 
Permanently discontinue bevacizumab. 
5.9.9. 
Monitoring and Management of Bevacizumab-Associated Bleeding 
Patients receiving bevacizumab should be monitored for signs and symptoms of CNS bleeding. 
Signs and symptoms include sudden and severe headache, headache associated with a recent 
blow to the head, mild and long-lasting headache, headache accompanied by neck stiffness, 
confusion, drowsiness, vomiting (more than two episodes in 24 hours), seizures, and coma. 
Bevacizumab should be discontinued for intracranial bleeding of any grade. If Grade 3 or 
Grade 4 bleeding of any kind occurs in a patient receiving bevacizumab during the study 
treatment period, bevacizumab should be permanently discontinued. If hemorrhagic 
complications occur in a patient on full-dose anticoagulation therapy, bevacizumab should be 
permanently discontinued, and the patient should be treated per institutional guidelines. Standard 
procedures such as antagonization with protamine or vitamin K, infusion of vitamin K dependent 
factors, or insertion of a vena cava filter should be considered, depending on the severity of the 
bleeding, the presence of thrombotic events, and the organ affected. 
5.9.10. 
Monitoring and Management of Bevacizumab-Associated Gastrointestinal 
Fistula/Perforation 
Patients receiving bevacizumab should be continually monitored for signs or symptoms of GI 
fistula/bowel perforation. Perforations have been shown to occur at a higher frequency in 
patients who have received pelvic radiation therapy. Signs and symptoms of bowel perforation 
include fever, nausea, vomiting, hematemesis, chills, and severe stomach pain. Signs and 
symptoms of GI fistula include abdominal pain, painful bowel obstruction, fever, and elevated 
white blood cell counts. Other symptoms include diarrhea, rectal bleeding, sepsis, dehydration, 
poor absorption of nutrients, and weight loss. Patients are advised to notify their treating 
physician immediately if they experience any of the signs or symptoms described above. If a 
positive diagnosis of GI fistula or perforation is made, bevacizumab should be immediately 
discontinued, and the patient should be treated per institutional guidelines. 
5.9.11. 
Monitoring and Management of Peripheral Neuropathy 
Peripheral sensory neuropathy is a common AE observed in patients receiving bevacizumab in 
combination with paclitaxel or oxaliplatin. When mirvetuximab soravtansine is administered as a 
single agent, peripheral neuropathy is a common AE (mirvetuximab soravtansine 
Investigator Brochure). Patients should be monitored for signs and symptoms of peripheral 
neuropathy.  
If a patient is diagnosed with peripheral neuropathy, the management guidelines in Table 14 
should be followed. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
74 
Table 14: 
Management Guidelines for Peripheral Neuropathy 
Severity Grade 
(CTCAE Version 
4.03 Grade) 
Management 
Guidelines for Mirvetuximab 
Soravtansine Dose Modifications 
Grade 1 
• Monitor signs and symptoms. 
• Continue mirvetuximab soravtansine 
dosing. 
• Continue bevacizumab, carboplatin, or 
pegylated liposomal doxorubicin dosing. 
Grade 2 
• Monitor patient until 
resolution to Grade 1 or 
baseline.  
• Treat patient per institutional 
guidelines. 
• Hold mirvetuximab soravtansine dosing 
until resolution to Grade 1 or baseline.  
• Patients with peripheral neuropathy 
lasting ≤ 14 days will resume 
mirvetuximab soravtansine therapy at the 
same dose level.  
• Patients with peripheral neuropathy who 
experience dosing delays > 14 days will 
resume mirvetuximab soravtansine 
treatment at a reduced dose level except 
if in Regimen B and second occurrence. 
If second occurrence and Regimen B, 
mirvetuximab soravtansine will resume at 
the same dose level.  
• Continue bevacizumab or pegylated 
liposomal doxorubicin dosing. 
• Continue carboplatin dosing if first 
occurrence.  
• Hold dosing of carboplatin until resolution 
to Grade 1 if second occurrence. Once 
resolved to Grade 1, carboplatin will 
resume at a reduced dose level.  
Table 14: 
Management Guidelines for Peripheral Neuropathy (Continued) 
Severity Grade 
(CTCAE Version 
4.03 Grade) 
Management 
Guidelines for Mirvetuximab 
Soravtansine Dose Modifications 
Grade 3 
• Monitor patient until 
resolution to Grade 1 or 
baseline. 
• Treat patient per institutional 
guidelines. 
• Hold mirvetuximab soravtansine dosing 
until resolution to Grade 1 or baseline.  
• Patients will resume mirvetuximab 
soravtansine at a lower dose level except 
if in Regimen B and second occurrence. 
If second occurrence and Regimen B, 
mirvetuximab soravtansine will resume at 
the same dose level.  
• Continue bevacizumab or pegylated 
liposomal doxorubicin dosing. 
• Hold dosing of carboplatin until resolution 
to Grade 1 if second occurrence. Once 
resolved to Grade 1, carboplatin will 
resume at a reduced dose level. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
75 
Severity Grade 
(CTCAE Version 
4.03 Grade) 
Management 
Guidelines for Mirvetuximab 
Soravtansine Dose Modifications 
Grade 4 
• Monitor patient until 
resolution to Grade 1 or 
baseline. 
• Treat patient per institutional 
guidelines. 
• Permanently discontinue mirvetuximab 
soravtansine dosing. 
• Permanently discontinue bevacizumab 
dosing. 
• Permanently discontinue carboplatin 
dosing. 
• Permanently discontinue pegylated 
liposomal doxorubicin dosing. 
5.9.12. 
Monitoring and Management of Pembrolizumab-Associated Type 1 Diabetes 
Mellitus 
For Type 1 diabetes mellitus (T1DM) or Grade 3 to 4 hyperglycemia: 
• Insulin replacement therapy is recommended for T1DM and for Grade 3 to 4 
hyperglycemia associated with metabolic acidosis or ketonuria.  
• Evaluate patients with serum glucose and a metabolic panel, urine ketones, 
glycosylated hemoglobin, and C-peptide.  
Refer to Table 21 for dose modifications and discontinuation of pembrolizumab. 
5.9.13. 
Monitoring and Management of Pembrolizumab-Associated Hypophysitis 
• For Grade 2 events, treat with corticosteroids. When symptoms improve to Grade 1 or 
less, steroid taper should be started and continued over no fewer than 4 weeks. 
Replacement of appropriate hormones may be required as the steroid dose is tapered. 
• For Grade 3 to 4 events, treat with an initial dose of IV corticosteroids followed by 
oral corticosteroids. When symptoms improve to Grade 1 or less, steroid taper should 
be started and continued over no fewer than 4 weeks. Replacement of appropriate 
hormones may be required as the steroid dose is tapered. 
Refer to Table 21 for dose modifications and discontinuation of pembrolizumab. 
5.9.14. 
Monitoring and Management of Pembrolizumab-Associated Hyperthyroidism or 
Hypothyroidism 
Thyroid disorders can occur at any time during treatment. Monitor patients for changes in 
thyroid function (at the start of treatment, periodically during treatment, and as indicated based 
on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. 
• Grade 2 hyperthyroidism events (and Grade 2-4 hypothyroidism): 
− In hyperthyroidism, non-selective beta-blockers (eg, propranolol) are suggested as 
initial therapy. 
− In hypothyroidism, thyroid hormone replacement therapy, with levothyroxine or 
liothyronine, is indicated per standard of care. 
• Grade 3-4 hyperthyroidism: 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
76 
− Treat with an initial dose of IV corticosteroids followed by oral corticosteroids. 
When symptoms improve to Grade 1 or less, steroid taper should be started and 
continued over no fewer than 4 weeks. Replacement of appropriate hormones may 
be required as the steroid dose is tapered. 
Refer to Table 21 for dose modifications and discontinuation of pembrolizumab. 
5.9.15. 
Monitoring and Management of Pembrolizumab-Associated Hepatic Adverse 
Events 
• For Grade 2 events, monitor liver function tests more frequently until returned to 
baseline values (consider weekly). 
− Treat with IV or oral corticosteroids. 
• For Grade 3 to 4 events, treat with IV corticosteroids for 24 to 48 hours.  
• When symptoms improve to Grade 1 or less, a steroid taper should be started and 
continued over no fewer than 4 weeks. 
Refer Table 21 for dose modifications and discontinuation of pembrolizumab. 
5.9.16. 
Monitoring and Management of Pembrolizumab-Associated Renal Failure or 
Nephritis 
• For Grade 2 events, treat with corticosteroids. 
• For Grade 3 to 4 events, treat with systemic corticosteroids. 
• When symptoms improve to Grade 1 or less, steroid taper should be started and 
continued over no fewer than 4 weeks.  
Refer Table 21 for dose modifications and discontinuation of pembrolizumab. 
5.10. 
Treatment Guidelines 
5.10.1. 
Re-treatment Criteria 
In the absence of a DLT, for a patient to begin a new cycle or continue a cycle of therapy, the 
following criteria must be met. 
• ANC must be ≥ 1.5 × 109/L (1,500/µL) (Cycle 1 Day 1 only). 
• ANC must be ≥ 1.0 × 109/L (1,000/µL). 
• Platelet count must be ≥ 75 × 109/L (75,000/µL). 
• All non-hematologic toxicities for which a causal association to study treatment 
cannot be ruled out must be ≤ Grade 2 (except alopecia) or returned to baseline; the 
exceptions to this rule are: 
− Treatment-emergent ocular disorders, which must have recovered to ≤ Grade 1 or 
baseline. 
− Treatment-emergent pneumonitis, which must have recovered to ≤ Grade 1 within 
one cycle. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
77 
− Treatment-emergent hypertension must have recovered to blood pressure of 
< 150/100 mm Hg (Regimen A and Regimen E only). 
− Treatment-emergent proteinuria must have recovered to ≤ Grade 1 (Regimen A 
and Regimen E only). 
− Treatment-emergent HFS must have recovered to ≤ Grade 1 (Regimen C). 
− Treatment-emergent mucositis must have recovered to ≤ Grade 1 (Regimen C). 
− Treatment-emergent, pembrolizumab-associated diarrhea/colitis must have 
recovered to ≤ Grade 1 (Regimen D). 
− Treatment-emergent, pembrolizumab-associated increased AST, ALT, and/or 
total bilirubin must have recovered to ≤ Grade 1 (Regimen D). 
− Treatment-emergent, pembrolizumab-associated hypophysitis must have 
recovered to ≤ Grade 1 (Regimen D). 
− Treatment-emergent, pembrolizumab-associated renal failure/nephritis must have 
recovered to ≤ Grade 1 (Regimen D). 
− Treatment-emergent, pembrolizumab-associated infusion reaction must have 
recovered to ≤ Grade 1 (Regimen D). 
If the patient does not meet these criteria, dosing with the two agents in the combination 
Regimen will be delayed, and the patient should be re-evaluated within 48 to 72 hours. Dosing 
with both agents may resume if these criteria have been met. If the AE can be attributed to one of 
the agents in the combination Regimen, that agent will be held or discontinued per the dose 
modification guidelines described in Section 5.10.4; however, treatment with the second agent 
may resume provided all the other criteria are met. However, if the next cycle is delayed by 
greater than 14 days because of insufficient recovery from a treatment-related toxicity, this will 
be viewed as a DLT (Section 4.1.4). If the next cycle is delayed longer than one cycle because of 
treatment-related toxicity, the patient should be removed from study treatment. In such cases, 
continuation of study treatment may be considered for those patients who have experienced 
clinical benefit if agreed upon between the Sponsor and the Investigator.  
The use of granulocyte growth factors in accordance with ASCO guidelines may be implemented 
at the discretion of the treating physician after Cycle 1. 
5.10.2. 
Follow-up for Dose-Limiting Toxicities and Adverse Events Leading to 
Discontinuation 
Patients who experience a non-laboratory DLT must be evaluated weekly, at a minimum, until 
resolution to ≤ Grade 1 or baseline and then at least monthly until return to baseline or 
stabilization of the event, whichever comes first. For abnormal laboratory values that qualify as a 
DLT, patients will be followed twice weekly until values return to < Grade 1 or baseline, 
whichever comes first. 
Patients who discontinue study treatment for an AE or an abnormal laboratory value must be 
followed per standard of care at least once a week for 4 weeks, and subsequently at 4-week 
intervals until resolution or stabilization of the AE or laboratory abnormality, whichever occurs 
first.  


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
78 
5.10.3. 
Criteria for Re-initiation of Study Treatment After Occurrence of a Dose-
Limiting Toxicity  
Study treatment will be stopped if a patient experiences a DLT at any time during the study. It 
may resume, with applicable dose adjustments (Section 5.10.4.1), if the following criteria are met: 
• ANC must be ≥ 1.0 × 109/L (1,000/µL). 
• Platelet count must be ≥ 75 × 109/L (75,000/µL). 
• All clinically significant non-hematologic toxicities for which a causal association to 
study treatment cannot be ruled out must be ≤ Grade 1 (except alopecia) or returned 
to baseline. 
If the patient does not meet these criteria, dosing will be delayed, and the patient should be 
re-evaluated within 48 to 72 hours. Dosing may resume if these criteria have been met. However, 
if the next cycle is delayed by greater than 14 days because of insufficient recovery from a 
treatment-related toxicity, this may be viewed as a DLT (Section 4.1.4). If the next cycle is 
delayed longer than one cycle because of treatment-related toxicity, the patient should be 
removed from study treatment. In such cases, continuation of study treatment may be considered 
for those patients who have experienced clinical benefit if agreed upon by the Sponsor and the 
Investigator. 
5.10.4. 
Dose Modification Guidelines 
5.10.4.1. Mirvetuximab Soravtansine Dose Reduction After a Dose-Limiting Toxicity  
Mirvetuximab soravtansine dose may be reduced at the discretion of the Investigator after 
discussion with the Sponsor. Patients who develop DLTs or AEs requiring an interruption of 
mirvetuximab soravtansine may resume treatment at a reduced dose level as shown in Table 15, 
provided the criteria outlined in Section 5.10.1 are met. 
Table 15: 
Mirvetuximab Soravtansine Dose Modification Guidelines 
Regimen 
If the Patient Was Receiving Mirvetuximab 
Soravtansine at: 
Dose Should Be Reduced to: 
A, B, C, D, 
or E 
6.0 mg/kg 
5.0 mg/kg 
5.0 mg/kg 
4.0 mg/kg 
Reduction of the mirvetuximab soravtansine dose below 4.0 mg/kg will not be permitted. Dose reductions to 
intermediate dose levels may be allowed on the basis of emerging data with the approval of the Sponsor. 
5.10.4.2. Bevacizumab Dose Modification Guidelines 
5.10.4.2.1. Grade 3 or Grade 4 Adverse Events 
Bevacizumab should be temporarily withheld for Grade 4 febrile neutropenia and/or Grade 4 
thrombocytopenia (regardless of the causal relationship to treatment) because these conditions 
are predisposing factors for bleeding. If a patient experiences a Grade 3 venous 
thromboembolism, bevacizumab must be withheld for 3 weeks. Bevacizumab may be resumed 
during the period of therapeutic-dose anticoagulant therapy. In general, Grade 3 or Grade 4 
bevacizumab-related events should be managed as outlined in Table 16. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
79 
Table 16: 
Bevacizumab Dose Modification Guidelines 
First occurrence of Grade 3 or 4 AE 
Hold bevacizumab until toxicity has improved to ≤ Grade 1. 
Second occurrence of Grade 3 or 4 AE 
Permanently discontinue bevacizumab treatment. 
5.10.4.3. Pegylated Liposomal Doxorubicin Dose Modification Guidelines for 
Non-hematologic Adverse Events 
5.10.4.3.1. General Guidelines 
If patients receiving pegylated liposomal doxorubicin experience non-hematologic, treatment-
related AEs, their pegylated liposomal doxorubicin dose should be reduced as indicated in 
Table 17. Patients who require dose reductions below 20 mg/m2 should discontinue pegylated 
liposomal doxorubicin treatment. 
Table 17: 
Dose Modification Guidelines for Pegylated Liposomal Doxorubicin for Non-
hematologic Adverse Events 
If the Patient Was Receiving Pegylated Liposomal Doxorubicin at: 
Dose Should Be Reduced 
to: 
40.0 mg/m2 
35.0 mg/m2 
35.0 mg/m2 
30.0 mg/m2 
30.0 mg/m2 
20.0 mg/m2 
Reduction of the pegylated liposomal doxorubicin dose below 20.0 mg/m2 will not be permitted. 
5.10.4.3.2. Pegylated Liposomal Doxorubicin Dose Reductions for Hematologic Adverse 
Events 
Patients receiving pegylated liposomal doxorubicin are at risk of bone marrow suppression. 
Leukopenia is usually transient; hematologic AEs may require dose delays or reductions as 
indicated in Table 18. 
Table 18: 
Pegylated Liposomal Doxorubicin Dose Reduction for Hematologic Adverse 
Events 
Severity Grade  
(CTCAE Version 4.03 Grade) 
Dose Modification 
Grade 1 
No action required. 
Grade 2 and Grade 3 
Hold pegylated liposomal doxorubicin until ANC and platelet levels 
return to normal or improve to Grade 1. Resume dosing without 
dose reduction. 
Grade 4 
Hold pegylated liposomal doxorubicin until ANC and platelet levels 
return to normal or improve to Grade 1. Resume dosing at a 25% 
dose reduction or at full dose with cytokine support.  
5.10.4.3.3. Dose Reductions for Pegylated Liposomal Doxorubicin Hand-Foot Syndrome 
and/or Mucositis 
Hand-foot syndrome is a disease characterized by palmar-plantar skin eruptions with swelling, 
pain, erythema, and for some patients, desquamation of the skin of the hands and feet. Hand-foot 
syndrome has been observed in patients receiving pegylated liposomal doxorubicin at doses of 
50 mg/m2 and, with less frequency, in those receiving pegylated liposomal doxorubicin at 
30 mg/m2. If patients present with symptoms/signs consistent with HFS, the dose of pegylated 
liposomal doxorubicin should be modified as indicated in Table 19. 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
80 
Table 19: 
Pegylated Liposomal Doxorubicin Dose Modification Guidelines for Hand and Foot 
Syndrome and Mucositis 
Severity Grade 
(CTCAE 
Version 4.03 
Grade) 
HFS  
Symptoms 
Mucositis 
Symptoms 
Dose Reduction/Discontinuation 
Grade 1 
Mild erythema, swelling, or 
desquamation not 
interfering with daily 
activities 
Painless 
ulcers, 
erythema, or 
mild soreness 
Continue pegylated liposomal 
doxorubicin, unless previous Grade 
3 or 4 HFS.  
In case of previous Grade 3 or 4 
HSF, delay up to 2 weeks and 
decrease dose by 25%.  
Grade 2 
Erythema, desquamation, 
or swelling interfering with, 
but not precluding, normal 
physical activities; small 
blisters or ulcerations less 
than 2 cm in diameter 
Painful 
erythema, 
edema, or 
ulcers, but can 
eat 
Hold pegylated liposomal 
doxorubicin until resolved to Grade 
1 or baseline. If no resolution after 
2 weeks, pegylated liposomal 
doxorubicin should be 
discontinued. If no prior Grade 3-4 
HFS, resume at the dose before 
the event. If previous HFS Grade 
3-4 toxicity, decrease dose by 
25%. 
Grade 3 
Blistering, ulceration, or 
swelling interfering with 
walking or normal daily 
activities; cannot wear 
regular clothing 
Painful 
erythema, 
edema, or 
ulcers; cannot 
eat 
Hold pegylated liposomal 
doxorubicin until resolved to Grade 
1 or baseline. Decrease dose by 
25%. . If no resolution after 
2 weeks, pegylated liposomal 
doxorubicin should be 
discontinued. 
Grade 4 
Diffuse or local process 
causing infectious 
complications, a bed ridden 
state, or hospitalization 
Requires 
parenteral or 
enteral support 
5.10.4.4. Carboplatin Dose Modification Guidelines 
Severe myelosuppression, GI effects (vomiting and nausea), and peripheral neuropathy 
(paresthesia) have been frequently observed in patients treated with carboplatin.  
Refer to Table 5 and Table 20 for specific guidelines regarding carboplatin dose reductions. 
Table 20: 
Dose Modification Guidelines for Carboplatin 
If the Patient Was Receiving Carboplatin at: 
Dose Should Be Reduced to: 
AUC5 
AUC4 
AUC4 
Discontinue 
5.10.4.5. Dose Modification and Toxicity Management for Immune-Related Adverse Events 
Associated With Pembrolizumab  
Adverse events associated with pembrolizumab exposure may represent an immunologic 
etiology. These immune-related AEs (irAEs) may occur shortly after the first dose or several 
months after the last dose of pembrolizumab treatment and may affect more than one body 
system simultaneously. Therefore, early recognition and initiation of treatment is critical to 
reduce complications. Based on existing clinical study data, most irAEs were reversible and 
could be managed with interruptions of pembrolizumab, administration of corticosteroids, and/or 
other supportive care. For suspected irAEs, ensure adequate evaluation to confirm etiology or 


mirvetuximab soravtansine 
 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
81 
exclude other causes. Additional procedures or tests such as bronchoscopy, endoscopy, or skin 
biopsy may be included as part of the evaluation. On the basis of the severity of irAEs, withhold 
or permanently discontinue pembrolizumab and administer corticosteroids. Dose modification 
and toxicity management guidelines for irAEs associated with pembrolizumab are provided in 
Table 21. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
82 
Table 21: 
Dose Modification and Toxicity Management Guidelines for Immune-Related Adverse Events Associated With 
Pembrolizumab 
General Instructions 
Corticosteroid taper should be initiated upon AE improving to Grade 1 or less and continue to taper over at least 4 weeks. 
For situations where pembrolizumab has been withheld, pembrolizumab can be resumed after AE has been reduced to Grade 1 or 0 
and corticosteroid has been tapered. Pembrolizumab should be permanently discontinued if AE does not resolve within 12 weeks of 
last dose or corticosteroids cannot be reduced to ≤ 10 mg prednisone or equivalent per day within 12 weeks.  
For severe and life-threatening irAEs, IV corticosteroid should be initiated first, followed by oral steroid. Other immunosuppressive 
treatment should be initiated if irAEs cannot be controlled by corticosteroids. 
Immune-Related AEs 
Toxicity Grade or 
Conditions (CTCAE 
Version 4.0) 
Action Taken 
With 
Pembrolizumab 
irAE Management With 
Corticosteroid and/or 
Other Therapies 
Monitor and Follow-up 
Pneumonitis 
Grade 2 
Withhold  
Administer corticosteroids 
(initial dose of 1-2 mg/kg 
prednisone or 
equivalent), followed by 
taper. 
Monitor participants for signs and symptoms 
of pneumonitis. 
Evaluate participants with suspected 
pneumonitis with radiologic imaging, and 
initiate corticosteroid treatment. 
Add prophylactic antibiotics for opportunistic 
infections. 
Grade 3 or 4, or 
recurrent Grade 2 
Permanently 
discontinue 
Diarrhea/colitis 
Grade 2 or 3 
Withhold 
Administer corticosteroids 
(initial dose of 1-2 mg/kg 
prednisone or 
equivalent), followed by 
taper. 
Monitor participants for signs and symptoms 
of enterocolitis (ie, diarrhea, abdominal 
pain, or blood or mucus in stool, with or 
without fever) and bowel perforation (ie, 
peritoneal signs and ileus). 
Participants with ≥ Grade 2 diarrhea 
suspecting colitis should consider GI 
consultation and performing endoscopy to 
rule out colitis.  
Participants with diarrhea/colitis should be 
advised to drink liberal quantities of clear 
fluids. If sufficient oral fluid intake is not 
feasible, fluid and electrolytes should be 
substituted via IV infusion. 
Grade 4 
Permanently 
discontinue 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
83 
Table 21: 
Dose Modification and Toxicity Management Guidelines for Immune-Related Adverse Events Associated With 
Pembrolizumab (Continued) 
Immune-Related AEs 
Toxicity Grade or 
Conditions (CTCAE 
Version 4.0) 
Action Taken 
With 
Pembrolizumab 
irAE Management With 
Corticosteroid and/or 
Other Therapies 
Monitor and Follow-up 
AST/ALT elevation or 
increased bilirubin 
Grade 2 
Withhold 
Administer corticosteroids 
(initial dose of 0.5-1 
mg/kg prednisone or 
equivalent), followed by 
taper. 
Monitor with liver function tests (consider 
weekly or more frequently until liver enzyme 
value returns to baseline or is stable). 
Grade 3 or 4  
Permanently 
discontinue 
Administer corticosteroids 
(initial dose of 1-2 mg/kg 
prednisone or 
equivalent), followed by 
taper. 
T1DM or 
hyperglycemia 
New onset T1DM or 
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of β-cell 
failure 
Withhold 
Initiate insulin 
replacement therapy for 
participants with T1DM.  
Administer anti-
hyperglycemic in 
participants with 
hyperglycemia. 
Monitor participants for hyperglycemia or 
other signs and symptoms of diabetes. 
Hypophysitis 
Grade 2 
Withhold 
Administer corticosteroids 
and initiate hormonal 
replacements as clinically 
indicated.  
Monitor for signs and symptoms of 
hypophysitis (including hypopituitarism and 
adrenal insufficiency). 
Grade 3 or 4  
Withhold or 
permanently 
discontinue  
Hyperthyroidism 
Grade 2 
Continue  
Treat with non-selective 
beta-blockers (eg, 
propranolol) or 
thionamides as 
appropriate. 
Monitor for signs and symptoms of thyroid 
disorders. 
Grade 3 or 4  
Withhold or 
permanently 
discontinue 
Hypothyroidism 
Grade 2-4 
Continue  
Initiate thyroid 
replacement hormones 
(eg, levothyroxine or 
liothyronine) per standard 
of care. 
Monitor for signs and symptoms of thyroid 
disorders. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
84 
Table 21: 
Dose Modification and Toxicity Management Guidelines for Immune-Related Adverse Events Associated With 
Pembrolizumab (Continued) 
Immune-Related AEs 
Toxicity Grade or 
Conditions (CTCAE 
Version 4.0) 
Action Taken 
With 
Pembrolizumab 
irAE Management With 
Corticosteroid and/or 
Other Therapies 
Monitor and Follow-up 
Nephritis and renal 
dysfunction 
Grade 2 
Withhold  
Administer corticosteroids 
(prednisone 1-2 mg/kg or 
equivalent) followed by 
taper. 
Monitor changes in renal function. 
Grade 3 or 4  
Permanently 
discontinue 
Myocarditis 
Grade 1 or 2 
Withhold 
On the basis of on 
severity of AE, administer 
corticosteroids. 
Ensure adequate evaluation to confirm 
etiology and/or exclude other causes. 
Grade 3 or 4 
Permanently 
discontinue 
All other immune-
related AEs 
Intolerable/persistent 
Grade 2 
Withhold 
On the basis of type and 
severity of AE, administer 
corticosteroids. 
Ensure adequate evaluation to confirm 
etiology and/or exclude other causes. 
Grade 3 
Withhold or 
discontinue on 
the basis of the 
type of event. 
Events that 
require 
discontinuation 
include, but are 
not limited to, 
Guillain-Barre 
syndrome, 
encephalitis. 
Grade 4 or recurrent 
Grade 3  
Permanently 
discontinue 
Withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician.  
Note: For participants with Grade 3 or 4 immune-related endocrinopathy where withholding pembrolizumab is required, pembrolizumab may be resumed when AE 
resolves to ≤ Grade 2 and is controlled with hormonal replacement therapy or metabolic control is achieved (in case of T1DM). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
85 
5.10.4.6. Dose Modification and Toxicity Management of Infusion Reactions Related to 
Pembrolizumab 
Pembrolizumab may cause severe or life-threatening infusion reactions including severe 
hypersensitivity or anaphylaxis. Signs and symptoms usually develop during or shortly after drug 
infusion and generally resolve completely within 24 hours after completion of infusion. Dose 
modification and toxicity management guidelines for pembrolizumab-associated infusion 
reactions are provided in Table 22. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
86 
Table 22: 
Pembrolizumab Infusion Reaction Dose Modification and Treatment Guidelines 
NCI CTCAE Grade 
Treatment 
Premedication at Subsequent Dosing 
Grade 1 
Mild reaction; infusion 
interruption not indicated; 
intervention not indicated 
Increase monitoring of vital signs as medically indicated until the 
participant is deemed medically stable in the opinion of the investigator. 
None 
Grade 2 
Requires therapy or 
infusion interruption but 
responds promptly to 
symptomatic treatment 
(eg, antihistamines, 
NSAIDs, narcotics, IV 
fluids); prophylactic 
medications indicated for 
≤ 24 h. 
Stop Infusion. 
Additional appropriate medical therapy may include but is not limited to: 
• 
IV fluids 
• 
Antihistamines 
• 
NSAIDs 
• 
Acetaminophen 
• 
Narcotics 
Increase monitoring of vital signs as medically indicated until the 
participant is deemed medically stable in the opinion of the investigator. 
If symptoms resolve within 1 hour of stopping drug infusion, the infusion 
may be restarted at 50% of the original infusion rate (eg, from 100 mL/h 
to 50 mL/h). Otherwise, dosing will be held until symptoms resolve, and 
the participant should be premedicated for the next scheduled dose. 
Participants who develop Grade 2 toxicity despite adequate 
premedication should be permanently discontinued from further 
study drug treatment. 
Participant may be premedicated 1.5 h 
(± 30 min) before infusion of 
pembrolizumab with: 
• 
Diphenhydramine 50 mg PO (or 
equivalent dose of antihistamine) 
• 
Acetaminophen 500-1000 mg PO 
(or equivalent dose of analgesic) 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
87 
Table 22: 
Pembrolizumab Infusion Reaction Dose Modification and Treatment Guidelines (Continued) 
NCI CTCAE Grade 
Treatment 
Premedication at Subsequent Dosing 
Grades 3 and 4 
Grade 3: 
Prolonged (ie, not rapidly 
responsive to 
symptomatic medication 
and/or brief interruption of 
infusion); recurrence of 
symptoms following initial 
improvement; 
hospitalization indicated 
for other clinical sequelae 
(eg, renal impairment, 
pulmonary infiltrates) 
Grade 4: 
Life-threatening; pressor 
or ventilator support 
indicated 
Stop Infusion. 
Additional appropriate medical therapy may include but is not limited to: 
• 
Epinephrine** 
• 
IV fluids 
• 
Antihistamines 
• 
NSAIDs 
• 
Acetaminophen 
• 
Narcotics 
• 
Oxygen 
• 
Pressors 
• 
Corticosteroids 
Increase monitoring of vital signs as medically indicated until the 
participant is deemed medically stable in the opinion of the investigator. 
Hospitalization may be indicated. 
**In cases of anaphylaxis, epinephrine should be used immediately. 
Participant is permanently discontinued from further study drug 
treatment. 
No subsequent dosing 
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the period of drug administration. For further 
information, please refer to the CTCAE Version 4.0 at http://ctep.cancer.gov. 
NSAID = non-steroidal anti-inflammatory drug. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
88 
5.10.4.7. Hierarchy of Dose Reductions/Discontinuations 
Patients experiencing AEs that can be clearly attributed to mirvetuximab soravtansine or to any 
of the combination drugs will have the corresponding agent reduced first (Table 23). In case of 
an AE recurrence, the other drug in the combination Regimen will then be dose reduced. If the 
relationship of an AE to a particular drug cannot be clearly determined, the order in which the 
drugs are to be reduced will require approval from the Sponsor. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
89 
Table 23: 
Agent to be Dose Reduced/Discontinued First on the Basis of Reported 
Compound-Specific Treatment-Related Adverse Events 
Adverse Event 
Mirvetuximab 
Soravtansine 
Combination Agent 
Bevacizumab 
Carboplatin 
Pegylated 
Liposomal 
Doxorubicin 
Pembrolizumab 
Ocular 
symptoms 
● 
 
 
 
 
GI events 
(vomiting, 
nausea, 
diarrhea, 
abdominal pain, 
and constipation) 
● 
 
 
 
 
Peripheral 
neuropathy 
events 
● 
 
 
 
 
Noninfectious 
pneumonitis 
● 
 
 
 
● 
Anemiaa 
● 
 
● 
 
 
Metabolic 
disorders  
● 
 
 
 
 
Infusion-related 
reactions 
See Section 5.9.1. 
CNS 
hemorrhage 
 
● 
 
 
 
Hemorrhage 
 
● 
 
 
 
Hypertension 
 
● 
 
 
 
Proteinuria 
 
● 
 
 
 
PRES 
 
● 
 
 
 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
90 
Table 23: 
Agent to be Dose Reduced/Discontinued First on the Basis of Reported 
Compound-Specific Treatment-Related Adverse Events (Continued) 
Adverse Event 
Mirvetuximab 
Soravtansine 
Combination 
Agent 
AE 
Mirvetuximab 
Soravtansine 
Combination 
Agent 
GI perforation or fistula 
 
● 
 
 
 
Non-GI fistula 
 
● 
 
 
 
Tracheoesophageal fistula 
 
● 
 
 
 
Thromboembolism 
 
● 
 
 
 
HFS 
 
 
 
● 
 
Stomatitis 
 
 
 
● 
 
Neutropenia 
 
 
● 
● 
 
Thrombocytopenia 
 
 
● 
● 
 
Colitis 
 
 
 
 
● 
T1DM 
 
 
 
 
● 
Hypophysitis 
 
 
 
 
● 
Hyperthyroidism/ 
hypothyroidism 
 
 
 
 
● 
Renal failure or nephritis 
 
 
 
 
● 
AST, ALT, or increased 
bilirubin 
 
 
 
 
● 
a If patients are receiving mirvetuximab soravtansine in combination with carboplatin, then carboplatin should be 
reduced first. 
If the relationship of the AE to a particular drug cannot be clearly determined, the order in which the drugs are to be 
reduced will require approval from the Sponsor. 
5.10.5. 
Discontinuation of Study Treatment Due to Adverse Events 
Each drug in the combination Regimen may be discontinued independently on the basis of 
tolerance and drug-specific toxicities. If a doublet combination agent is discontinued in 
Regimen A (mirvetuximab soravtansine + bevacizumab), Regimen B (mirvetuximab 
soravtansine + carboplatin), Regimen C (mirvetuximab soravtansine + pegylated liposomal 
doxorubicin), or Regimen D (mirvetuximab soravtansine + pembrolizumab), the patient may 
continue participation in the study on mirvetuximab soravtansine as monotherapy. If a patient 
receiving Regimen A discontinues mirvetuximab soravtansine, the patient may continue 
participation in the study on bevacizumab as monotherapy until a reason for discontinuation 
arises (toxicity or tumor progression). If a patient receiving Regimen D discontinues 
mirvetuximab soravtansine, the patient may continue participation in the study on 
pembrolizumab as monotherapy until either the patient has received 35 treatments 
(approximately 2 years) or a reason for discontinuation arises (toxicity or tumor progression). If 
one or two of the components of the triplet dose (Regimen E) is/are discontinued, the patient 
may continue participation in the study with a doublet/single-agent therapy. For patients 
receiving either Regimen B or Regimen C, if mirvetuximab soravtansine is discontinued, the 
patient must be discontinued from the study. If patients receiving Regimen E discontinue all drug 
treatment because of toxicity, they will continue to be followed until progression. 
For all drugs, study treatment should not be resumed in the case of the following 
treatment-related events. 
• ≥ Grade 3 cardiac event. 
• Other non-hematologic events of Grade 4 severity. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
91 
• Failure to meet re-treatment criteria within one cycle due to insufficient recovery 
from a treatment-related toxicity. In such cases, continuation of study treatment may 
be considered for those patients who have experienced clinical benefit if agreed upon 
by the Sponsor and the Investigator. 
5.10.6. 
Additional Discontinuation Guidelines 
5.10.6.1. Pegylated Liposomal Doxorubicin Discontinuation 
Pegylated liposomal doxorubicin should be discontinued if the patient’s left ventricular ejection 
fraction drops below normal or by at least 15% from the baseline value. 
5.10.6.2. Bevacizumab Discontinuation 
Bevacizumab should be permanently discontinued in patients experiencing the AEs listed in 
Table 24. 
Table 24: 
Adverse Events Requiring Permanent Discontinuation of Bevacizumab 
Severity Grade  
(CTCAE Version 4.03 Grade) 
Adverse Event 
Any grade 
PRES  
Grade 3 or 4 
Hemorrhage or bleeding  
Grade 4 
Venous thromboembolism 
Any grade 
Arterial thromboembolism 
Any grade 
CNS bleeding 
Grade 4 
Proteinuria 
Grade 3 or 4 
Left ventricular dysfunction 
Grade 3 or 4 
Congestive heart failure 
Any grade 
GI perforation and fistula 
Any grade 
Tracheo-esophageal fistula 
Grade 4 
Non-GI fistula 
Any grade 
Hypersensitivity and/or allergic reactions to bevacizumab 
5.10.6.3. Carboplatin Discontinuation 
Carboplatin may be discontinued after six or more cycles at the discretion of the investigator 
on the basis of the benefit-risk profile for the patient. If carboplatin is discontinued, 
mirvetuximab soravtansine may be continued as a single agent for patients receiving 
Regimen B and in combination with bevacizumab for patients receiving Regimen E, if the 
patient continues to meet treatment criteria and has at least stable disease per RECIST 
Version 1.1.  
5.10.6.4. Pembrolizumab Discontinuation 
5.10.6.4.1. Discontinuation of Study Therapy After 2 Years 
Pembrolizumab will be discontinued after 35 treatments (approximately 2 years of treatment). 
Retreatment with pembrolizumab in combination with mirvetuximab soravtansine or as 
monotherapy may be considered if the patient has a CR and meets criteria in Section 5.10.6.4.2 
and Section 5.10.6.4.3. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
92 
5.10.6.4.2. Discontinuation of Study Therapy After Complete Response 
Discontinuation of treatment may be considered for patients who have attained a confirmed CR 
who have been treated for at least 24 weeks with mirvetuximab soravtansine and pembrolizumab 
and had at least 2 cycles of mirvetuximab soravtansine and pembrolizumab beyond the date 
when the initial CR was declared. Patients will follow the schedule of assessments in 
Appendix C. Patients who then experience radiologic PD may be eligible for up to 1 year of 
additional treatment with pembrolizumab in combination with mirvetuximab soravtansine or as 
monotherapy at the discretion of the Investigator if:  
• No cancer treatment was administered since the last dose of mirvetuximab 
soravtansine and pembrolizumab. 
• The patient meets the safety parameters listed in the inclusion/exclusion criteria 
(Section 3). 
• The study is still open. 
Patients will resume pembrolizumab in combination with mirvetuximab soravtansine or as 
monotherapy at the same dose and schedule at the time of initial discontinuation. Additional 
details are provided in Section 5.10.6.4.3. Response or progression during this re-treatment, 
termed the Second Course Phase (Section 5.10.6.4.3), will not count toward ORR or PFS for the 
primary endpoint in this trial. 
5.10.6.4.3. Second Course Phase 
Patients on Regimen D (mirvetuximab soravtansine + pembrolizumab) who stop mirvetuximab 
soravtansine and pembrolizumab with CR per Section 5.10.6.4.1 may be eligible for up to 1 year 
of additional treatment with pembrolizumab in combination with mirvetuximab soravtansine or 
as monotherapy if they progress after stopping study treatment. This Second Course Phase of this 
study is available only if the study remains open and the patient meets the following conditions: 
• Stopped initial treatment with mirvetuximab soravtansine and pembrolizumab after 
attaining an investigator-determined confirmed CR according to RECIST Version 
1.1. 
− Was treated for at least 24 weeks with mirvetuximab soravtansine and 
pembrolizumab before discontinuing therapy. 
− Received at least two treatments with mirvetuximab soravtansine and 
pembrolizumab beyond the date when the initial CR was declared. 
AND 
• Experienced Investigator-determined confirmed radiologic PD after stopping their 
initial treatment with mirvetuximab soravtansine and pembrolizumab. 
• Did not receive any anti-cancer treatment since the last dose of mirvetuximab 
soravtansine and pembrolizumab. 
• Has a performance status of 0 or 1 on the ECOG PS. 
• Demonstrates adequate organ function as detailed in the inclusion criteria 
(Section 3.1). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
93 
• If WCBP, defined as a sexually mature woman who has not undergone surgical 
sterilization or who has not been naturally postmenopausal for at least 12 consecutive 
months (ie, who has had menses any time in the preceding 12 consecutive months): 
has a negative serum or urine pregnancy test within 72 hours before receiving 
retreatment with study medication.  
• If WCBP: agrees to use effective contraceptive methods (examples include oral, 
parenteral, or implantable hormonal contraceptive, intra-uterine device, or 
vasectomy) while on study treatment and for at least 12 weeks after the last dose of 
mirvetuximab soravtansine and for at least 4 months after the last dose of 
pembrolizumab. 
• Does not have a history or current evidence of any condition, therapy, or laboratory 
abnormality that a) might interfere with the patient’s participation for the full duration 
of the study, or b) makes it not in the best interest of the patient to participate, in the 
opinion of the treating Investigator. 
Patients who restart treatment will be retreated at the same dose frequency as when they last 
received pembrolizumab and mirvetuximab soravtansine. Treatment will be administered for up 
to 1 additional year. Patients will follow the Schedule of Clinical Assessments in Appendix C.  
5.10.6.4.4. Discontinuation Due to Adverse Event 
Pembrolizumab must be permanently discontinued in patients experiencing the AEs listed in 
Table 25. 
Table 25: 
Adverse Events Requiring Discontinuation of Pembrolizumab 
Severity Grade  
(CTCAE Version 4.03 Grade) 
Adverse Event 
Grade 4  
Hyperthyroidism 
Grade 3 or 4 
Myocarditis 
Grade 3 or 4 
Pneumonitis 
Grade 3 or 4  
Infusion reaction 
Grade 3 or 4  
Renal failure/nephritis 
Grade 4 
Pembrolizumab-related adverse event 
5.11. 
Removal of the Patient From the Study or From Study Drug Administration 
The patient or legal guardian acting on behalf of the patient is free to withdraw consent and 
discontinue participation in the study at any time without prejudice to further treatment. For this 
protocol, patients withdrawn for reasons other than toxicity during Cycle 1 may be replaced. 
Patients will be removed from study treatment when their disease worsens and there is no 
clinical benefit. Additionally, a patient’s participation in the study may be discontinued at any 
time at the discretion of the Investigator. The following may be justifiable reasons for the 
Investigator to remove a patient from the study: 
• The patient suffers an intolerable AE. 
• Non-compliance, including failure to appear at one or more study visits. 
• The patient was erroneously included in the study. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
94 
• The study is terminated by the Sponsor. 
If a patient or the patient’s legal guardian(s), acting on behalf of the patient, discontinues 
participation in the study, or the patient is discontinued by the Investigator, the reason for 
discontinuation must be captured in the eCRF. Any AEs experienced up to the point of 
discontinuation must be documented on the AE eCRF. All serious adverse events (SAEs), and 
those AEs assessed by the Investigator as at least possibly related to study drug, should continue 
to be followed until they resolve or stabilize, whichever comes first. 
5.11.1. 
Replacement of Patients Who Are Withdrawn Before the End of Cycle 1 
Only patients who sign the ICF and receive at least one dose of mirvetuximab soravtansine will 
be considered enrolled. If an enrolled patient is discontinued from study treatment for reasons 
other than safety (eg, withdrawal of consent, non-compliance, death due to PD) before the end of 
Cycle 1, the patient will be replaced (ie, an additional patient will be added to the Dose 
Escalation dose level or Dose Expansion Cohort or triplet dose [Regimen E]). Patients who do 
not complete Cycle 1 because of an AE will not be replaced. Patients who are replaced will not 
be considered in making dose escalation decisions or safety decisions for dose expansion but, if 
possible, will be followed for safety and other assessments according to the protocol. 
5.12. 
Period of Observation 
The period of safety observation for this study extends from the time of informed consent until 
the final evaluation during the study, including the 30-day follow-up safety visit and 120 days 
after the last dose of pembrolizumab (Regimen D only). Short-term follow-up for patients who 
discontinue study therapy without documented PD will continue every 3 months until the 
patient’s disease worsens, until the patient begins subsequent anti-cancer treatment, or until the 
patient dies, whichever occurs first. 
5.13. 
Concomitant Medications and Procedures 
All concomitant medications and supportive therapy taken within 4 weeks before Cycle 1 Day 1 
and through 30 days after last study treatment must be recorded on the appropriate eCRF. The 
identity of all medications, dosage, and route of administration, frequency, duration of 
administration, and indication for use will be recorded in the appropriate sections of the eCRF. 
5.13.1. 
Antiemetic and Antidiarrheal Medications 
Antiemetic (eg, 5-HT3 [5-hydroxytryptamine type 3] serotonin receptor antagonists such as 
palonosetron, granisetron, or ondansetron) and antidiarrheal (eg, loperamide) medications may 
be used at the discretion of the treating physician. 
5.13.2. 
Folate-Containing Vitamins 
Folate-containing vitamins are not to be taken during the course of the study. 
5.13.3. 
Antineoplastic Therapy 
Other chemotherapy, investigational agents other than pembrolizumab (Regimen D only), 
immunotherapy, or biologic therapy will not be permitted during the study. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
95 
Palliative radiotherapy during study treatment should be discussed with the Sponsor before 
implementation. If the Investigator and Sponsor agree it is in the best interest of the patient, 
palliative radiotherapy may be performed; however, the patient will be censored in the PFS 
analysis from the time radiotherapy was performed if treatment was performed on a target or 
non-target lesion. 
5.13.4. 
Hematopoietic Growth Factors 
Patients receiving recombinant erythropoietin or darbepoetin-α before the study start may 
continue to receive pre-treatment doses.  
The use of erythropoietic and granulocyte growth factors in accordance with ASCO guidelines 
may be implemented at the discretion of the treating physician after Cycle 1. 
5.13.5. 
Medications Metabolized Through Cytochrome P450 3A 
In vitro metabolism studies demonstrated that DM4 is predominantly metabolized by thiol s-
methyltransferase to form S-methyl DM4, which is further metabolized into sulfoxide-methyl-
DM4. As S-methyl DM4 has been shown to be primarily metabolized by cytochrome P450 
(CYP) 3A, its exposure could potentially be increased in the presence of strong CYP3A 
inhibitors. Drinking more than one serving (250 mL) of grapefruit juice per day should be 
avoided. 
Available in vitro metabolism data suggest that DM4 has a potential to inhibit CYP3A activity in 
vivo. The risk of a significant in vivo drug-drug interaction caused by DM4 inhibition of CYP3A 
is not currently known; therefore, treatment of patients with concomitant medications that are 
sensitive substrates of CYP3A or are CYP3A substrates with a narrow therapeutic index 
(Appendix N) should be carefully monitored. 
5.13.6. 
Vaccinations (Regimen D Only) 
Live vaccines within 30 days before the first dose of pembrolizumab and while participating in 
the study are not allowed. Examples of live vaccines include, but are not limited to, the 
following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) 
vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are 
allowed. However, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and 
are not allowed. 
5.13.7. 
Systemic Steroids (Regimen D Only) 
Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of 
clinical interest of suspected immunologic etiology or premedication before administration of 
study drugs are not allowed. The use of physiologic doses of corticosteroids may be approved 
after consultation with the Sponsor. Inhaled steroids are allowed for management of asthma. 
Topical steroids including corticosteroid eye drops as outlined in Section 5.8.2 are allowed.  
5.13.8. 
Other Concomitant Medications 
Medications for the treatment of AEs or cancer symptoms (eg, packed red blood cells and pain 
medications) are allowed. Prophylactic use of steroids and/or antihistamines will be considered if 
needed to alleviate mild to moderate infusion-related reactions. Additionally, medications (not 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
96 
addressed above) used to treat underlying medical conditions at study entry, including anti-
emetics and anti-diarrheals, will be allowed to continue.  
5.14. 
Overdose and Medication Error 
5.14.1. 
Overdose 
Mirvetuximab soravtansine: There is no known treatment/antidote available. Supportive 
measures should be instituted if an instance arises in which a patient suffers an overdose of any 
study drug. In the event of overdose, the patient should be observed closely for signs of toxicity. 
Bevacizumab, carboplatin, or pegylated liposomal doxorubicin: Please see the package inserts 
for treatment of overdose. Supportive measures should be instituted if an instance arises in which 
a patient suffers an overdose of any study drug. 
Pembrolizumab: For this trial, an overdose will be defined as ≥ 1,000 mg (5 times the dose) 
of pembrolizumab. No specific information is available on the treatment of overdose of 
pembrolizumab.  
Overdose involving any of the study drugs, with or without associated AE/SAE, is to be recorded 
on the AE page of the eCRF and on an SAE form to ensure collection of the incident details, 
treatment, and any associated AEs. All instances of overdose must be reported to the sponsor as 
described for SAEs (Section 9.2.1). 
5.14.2. 
Medication Error  
The Sponsor must be notified immediately in the event of error in prescribing, dispensing, 
administering, and/or use of mirvetuximab soravtansine or any study drug. The event must be 
reported on the eCRF. If an error resulted in an SAE, an SAE Report Form must be submitted 
within 24 hours after the event (see Section 9.2). 
6. 
PHARMACOKINETIC AND IMMUNOGENEICITY ASSESSMENTS 
6.1. 
Pharmacokinetic Assessments 
Pharmacokinetic blood sample collection details are provided in Appendix D for each Regimen. 
Blood samples from patients will be analyzed to characterize the PK of mirvetuximab 
soravtansine when administered in 3- or 4-week cycles. This includes the analysis of intact 
conjugate, total antibody, DM4, and S-methyl DM4. Pharmacokinetic parameters include, but are 
not limited to, Cycle 1 and Cycle 3 Cmax, AUC, t½, CL, Vss, and tmax.  
Pre-infusion and post-infusion samples will be analyzed for pegylated liposomal doxorubicin, 
carboplatin, or bevacizumab concentrations. Samples may be analyzed to evaluate the 
concentration of pembrolizumab if warranted by a safety signal.  
NOTE: Any patient who experiences a ≥ Grade 2 infusion-related reaction during administration 
of mirvetuximab soravtansine will have blood drawn within 3 hours after the onset of the 
reaction and 1 week later for determination of drug concentration, antibodies to mirvetuximab 
soravtansine, and factors that may be related to the development of hypersensitivity reactions 
(see Section 5.9.1). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
97 
Pharmacokinetic samples may also be obtained as feasible at any time during the treatment 
period for assessment of treatment-related SAEs if deemed appropriate by the Investigator and 
Sponsor. 
When pre-dose samples are collected, they are to be taken before the start of the first 
infusion. 
6.1.1. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen A 
(Mirvetuximab Soravtansine + Bevacizumab)  
Blood Samples for Pharmacokinetic Measurements of Mirvetuximab Soravtansine 
Blood samples for PK measurements of mirvetuximab soravtansine will be taken at the 
following time points: 
Cycles 1 and 3 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes), and 6 hours after the completion of mirvetuximab 
soravtansine infusion (+ 20 minutes) 
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 3 – 48 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 8 – a single blood sample, which is collected when safety assessments are 
collected 
• Day 15 – a single blood sample, which is collected when safety assessments are 
collected 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) 
• End of treatment – a single blood sample, which is collected when safety 
assessments are collected 
• 30-day follow-up – a single blood sample, which is collected when safety 
assessments are collected 
Blood Samples for Pharmacokinetic Measurements of Bevacizumab 
Blood samples for PK measurements of bevacizumab will be taken at the following time points: 
Cycles 1 through 6 
• Day 1 – pre-dose and immediately after the completion of infusion of bevacizumab 
(+ 10 minutes) 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
98 
6.1.2. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen B 
(Mirvetuximab Soravtansine + Carboplatin) 
Blood Samples for Pharmacokinetic Measurements of Mirvetuximab Soravtansine 
Blood samples for PK measurements of mirvetuximab soravtansine will be taken at the 
following time points: 
Cycles 1 and 3 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) and 6 hours after the completion of mirvetuximab 
soravtansine infusion (+ 20 minutes) 
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 3 – 48 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 8 – a single blood sample, which is collected when safety assessments are 
collected 
• Day 15 – a single blood sample, which is collected when safety assessments are 
collected 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) 
• End of treatment – a single blood sample, which is collected when safety 
assessments are collected 
• 30-day follow-up – a single blood sample, which is collected when safety 
assessments are collected 
Blood Samples for Pharmacokinetic Measurements of Carboplatin 
Blood samples for PK measurements of carboplatin will be taken at the following time points: 
Cycles 1 and 3 
• Day 1 - pre-dose and immediately after the completion of infusion of carboplatin 
(+ 10 minutes) and 6 hours after the completion of mirvetuximab soravtansine 
infusion (+ 20 minutes)  
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of carboplatin 
(+ 10 minutes) 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
99 
6.1.3. 
Pharmacokinetic Assessments for 4-Week Cycle Regimen C (Mirvetuximab 
Soravtansine + Pegylated Liposomal Doxorubicin) 
Blood Samples for Pharmacokinetic Measurements of Mirvetuximab Soravtansine  
Blood samples for PK measurements of mirvetuximab soravtansine will be taken at the 
following time points: 
Cycles 1 and 3 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) and 6 hours after the completion of mirvetuximab 
soravtansine infusion (+ 20 minutes) 
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 3 – 48 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 8 – a single blood sample, which is collected when safety assessments are 
collected 
• Day 15 a single blood sample, which is collected when safety assessments are 
collected 
• Day 22 – a single blood sample, which is collected when safety assessments are 
collected 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes)  
• End of treatment – a single blood sample, which is collected when safety 
assessments are collected 
• 30-day follow-up – a single blood sample, which is collected when safety 
assessments are collected 
Blood Samples for Pharmacokinetic Measurements of Pegylated Liposomal Doxorubicin  
Blood samples for PK measurements of pegylated liposomal doxorubicin will be taken at the 
following time points: 
Cycles 1 through 6 
• Day 1 – pre-dose and immediately after the completion of infusion of pegylated 
liposomal doxorubicin (+ 10 minutes) 
6.1.4. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen D 
(Mirvetuximab Soravtansine + Pembrolizumab) 
Blood Samples for Pharmacokinetic Measurements of Mirvetuximab Soravtansine 
Blood samples for PK measurements of mirvetuximab soravtansine will be taken at the 
following time points: 
Cycles 1 and 3 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
100 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) and 6 hours after the completion of mirvetuximab 
soravtansine infusion (+ 20 minutes) 
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 3 – 48 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 8 – a single blood sample, which is collected when safety assessments are 
collected 
• Day 15 – a single blood sample, which is collected when safety assessments are 
collected 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) 
• End of treatment – a single blood sample, which is collected when safety 
assessments are collected 
• 30-day follow-up – a single blood sample, which is collected when safety 
assessments are collected 
Blood Samples for Pharmacokinetic Measurements of Pembrolizumab 
Blood samples for PK measurements of pembrolizumab will be taken at the following time 
points: 
Cycles 1 through 6 
• Day 1 – pre-dose and immediately after the completion of infusion of pembrolizumab 
(+ 10 minutes) 
6.1.5. 
Pharmacokinetic Assessments for 3-Week Cycle Schedule Regimen E 
(Mirvetuximab Soravtansine + Bevacizumab + Carboplatin) 
Blood Samples for Pharmacokinetic Measurements of Mirvetuximab Soravtansine 
Blood samples for PK measurements of mirvetuximab soravtansine will be taken at the 
following time points: 
Cycles 1 and 3 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) and 6 hours after the completion of mirvetuximab 
soravtansine infusion (+ 20 minutes) 
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 3 – 48 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
• Day 8 – a single blood sample, which is collected when safety assessments are 
collected 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
101 
• Day 15 – a single blood sample, which is collected when safety assessments are 
collected 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of mirvetuximab 
soravtansine (+ 10 minutes) 
• End of treatment – a single blood sample, which is collected when safety 
assessments are collected 
• 30-day follow-up – a single blood sample, which is collected when safety 
assessments are collected 
Blood Samples for Pharmacokinetic Measurements of Bevacizumab 
Blood samples for PK measurements of bevacizumab will be taken at the following time points: 
Cycles 1 through 6 
• Day 1 – pre-dose and immediately after the completion of infusion of bevacizumab 
(+ 10 minutes) 
Blood Samples for Pharmacokinetic Measurements of Carboplatin 
Blood samples for PK measurements of carboplatin will be taken at the following time points: 
Cycles 1 and 3 
• Day 1 - pre-dose and immediately after the completion of infusion of carboplatin 
(+ 10 minutes). 
• Day 2 – 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours) 
Cycles 2, 4, 5, and 6 
• Day 1 – pre-dose and immediately after the completion of infusion of carboplatin 
(+ 10 minutes) 
6.2. 
Immunogenicity Assessments of Mirvetuximab Soravtansine  
Mirvetuximab soravtansine immunogenicity will be assessed in plasma samples collected for PK 
evaluation; no additional blood draw is necessary. The following time points will be analyzed for 
ADA: before dosing (pre-dose) on Day 1 of Cycles 1, 2, 4, and 5; at the end of treatment and 
30-day follow-up visits.  
7. 
TRANSLATIONAL RESEARCH STUDIES 
Several biomarkers, including FRα, will be evaluated as potential biomarkers of clinical response 
to the different mirvetuximab soravtansine combination Regimens. These will help guide further 
clinical development of mirvetuximab soravtansine. 
7.1. 
Correlation Between FRα Expression and Mirvetuximab Soravtansine Anti-
tumor Activity 
FRα expression varies with tumor histology, as reported in the literature and demonstrated in 
ImmunoGen nonclinical studies (Section 1.1 and Investigator Brochure). On the basis of the 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
102 
hypothesis that tumors expressing higher levels of FRα are more likely to be susceptible to 
anti-tumor activity of mirvetuximab soravtansine, a threshold for FRα expression was 
determined for enrollment in this study. This was done on the basis of molecular epidemiology 
data generated in a number of patient samples representative of different tumor types, as well as 
clinical anti-tumor activity data from the FIH Study 0401. 
7.1.1. 
Evaluation of FRα Expression in Tumor Tissue During Dose Escalation and 
Dose Expansion 
FRα expression in tumors will be analyzed by IHC. All patients who are evaluated for this study 
must submit archived tumor tissue samples (either formalin-fixed, paraffin embedded blocks, or 
slides sectioned from such blocks), or new biopsy samples if archival samples are not available, 
for analysis of FRα expression by IHC before enrollment.  
For patients in Regimen D, the pre-dose biopsy, taken either during screening or on Cycle 1 
Day 1 (ie, a biopsy taken before the first dose of the study drug and before the first dose of 
combination drug) and the biopsy taken on Cycle 2 Day 8 (± 3) will also be submitted for FRα 
expression by IHC for biomarker research studies. 
If the biopsy procedure is considered to be of significant risk, the biopsy will not be taken. 
Significant risk procedures include (but are not limited to) biopsies of the brain, 
lung/mediastinum, or pancreas, and endoscopic procedures extending beyond the esophagus, 
stomach, or bowel.  
Only patients with the required FRα expression levels by IHC (either ≥ 25% or ≥ 50% [Protocol 
Amendment 4] of tumor staining at ≥ 2+ intensity) will be eligible to enroll in the study. If a 
patient wishes to enroll and does not have archival tumor tissue available for analysis, the patient 
must undergo a biopsy to obtain tumor tissue for FRα expression assessment. In this case, this 
biopsy will also serve as the pre-dose biopsy for the biomarker research study. If a biopsy 
procedure to obtain tumor tissue for a patient’s eligibility assessment is considered to be of 
significant risk, the patient cannot be enrolled in the study. 
The tumor samples will be analyzed for FRα expression in the Companion Diagnostics Pharma 
Services College of American Pathologists (CAP)-accredited and Clinical Laboratory 
Improvement Amendments (CLIA)-certified laboratory and Pathology Services at Ventana 
Medical Systems, Inc. Samples from patients on Regimens A (Cohorts 1 and 2), B, and C will 
have their FRα levels assessed using the FOLR1-RPA assay. Samples from patients on 
Regimens A (Cohort 3), D, and E will have their FRα levels assessed using the FOLR1-IUO 
assay. 
Immunohistochemistry data will be used to further define associations between FRα expression 
and clinical response. 
7.2. 
Exploratory Biomarker Studies 
Studies in tumor tissue and blood will be performed to explore potential markers of sensitivity 
and resistance to the mirvetuximab soravtansine combination Regimens. The sections below 
describe specific activities that are planned, but additional biomarkers/biological pathways may 
be investigated. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
103 
7.2.1. 
Potential Markers of Drug Response 
Cancer is a disease driven by molecular-level changes, which include mutations, DNA 
rearrangements, and copy number changes, and changes in the expression of proteins involved in 
key oncogenic pathways. Many of these changes determine or influence the aggressiveness of 
the disease, its response to therapy, and the development of resistance to treatment. To evaluate 
how these molecular changes are associated with response to the drug combinations, we will 
characterize the somatic mutations, gene rearrangements/fusions, and the gene expression profile 
of archival and biopsy tumor samples using a fit-for-purpose technology such as next-generation 
sequencing of tumor RNA and DNA. Mirvetuximab soravtansine, carboplatin, and pegylated 
liposomal doxorubicin target dividing cells; therefore, markers of cell proliferation including, but 
not limited to, Ki67 will be assessed in tumor samples from all patients. Potential associations 
between cell proliferation and clinical response will be examined. 
Mirvetuximab soravtansine retains the ADCC activity of the parental M9346A antibody. FcγR is 
the principal leukocyte receptor that mediates ADCC, and FcγR polymorphisms modulate 
leukocyte ADCC activity. Potential associations between FcγR genotype and clinical response 
will be examined (Appendix D). 
7.2.2. 
Potential Markers of Drug Resistance 
Drug efflux transporters and PgP in particular play an important role in cancer cell resistance to 
cytotoxic agents, including microtubule-targeting agents. Therefore, PgP expression levels and 
polymorphisms will be assessed as a marker of drug resistance in tumor tissues for all patients. 
Potential associations between PgP levels and clinical response will be examined. 
7.2.3. 
Potential Mechanism of Synergy Between Mirvetuximab Soravtansine and 
Pembrolizumab 
In several different tumor types, including melanoma, NSCLC, gastric cancer, and others, 
biomarkers have been identified that show positive correlation with response to PD-1/PD-L1 
inhibitors. These biomarkers include elevated expression of PD-L1, increased number of tumor-
infiltrating lymphocytes, and expression of immune-related gene signatures. To assess the 
potential of these biomarkers for predicting response to the combination of mirvetuximab 
soravtansine and pembrolizumab, IHC will be carried out for PD-L1 and markers for infiltrating 
lymphocytes such as CD3, CD4 and CD8, and expression of immune-related gene signatures 
will be assessed using next-generation sequencing of RNA. 
Recent nonclinical studies demonstrated that ADC with maytansinoid payload can enhance 
lymphocyte infiltration into tumor tissue, which partially contributed to the anti-tumor activity of 
ADC. Furthermore, a synergistic effect between ADC and multiple immune-checkpoint 
inhibitors was observed in vivo. Consistent with that, biopsies from patients with HER2-positive 
breast cancer before and after Kadcyla treatment demonstrated that treatment with Kadcyla 
resulted in an increased number of tumor-infiltrating T lymphocytes (Muller 2015). To evaluate 
the effect of mirvetuximab soravtansine and pembrolizumab treatment on immune cells, pre- and 
post-treatment biopsies will be stained for lymphocyte markers by IHC. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
104 
8. 
STUDY PROCEDURES 
8.1. 
Informed Consent 
Each patient or legally authorized representative must provide written informed consent before 
any study-required procedures are conducted, unless those procedures are performed as part of 
the patient’s standard care.  
8.2. 
Inclusion and Exclusion Criteria 
The inclusion and exclusion criteria will be assessed during screening. All screening evaluations 
must be completed and reviewed to confirm that potential patients meet all eligibility criteria. 
The Investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. Procedures conducted as 
part of the patient’s routine clinical management and obtained before signing an ICF may be 
used for screening or baseline purposes, provided the procedure met the protocol-specified 
criteria and was performed within the time frame defined in the Schedule of Clinical 
Assessments in Appendix A, Appendix B, and Appendix C. A patient is considered enrolled 
when administered the first dose of drug. 
8.3. 
Confirmation of Disease Diagnosis 
At screening, disease diagnosis and current disease status will be confirmed from information in 
the source record. 
8.4. 
Demographic/Medical History 
The age, race, and sex of the patient are to be recorded during screening. 
During the screening period, a complete medical history will be compiled for each patient. The 
history will include the background and progress of the patient’s primary malignancy and a 
description of all prior therapies for the primary malignancy. 
8.5. 
Physical Examination, Weight, and Height 
Physical examination, height (screening only), and weight must be performed as indicated in the 
Schedule of Clinical Assessments (Appendix A, Appendix B, and Appendix C).  
8.6. 
Vital Signs 
Vital signs will be measured at screening, before dosing on Day 1 of every cycle, and as 
indicated in Table 26 and Appendix A, Appendix B, and Appendix C. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
105 
Table 26: 
Vital Sign Measurements 
 
Scree
n-ing 
Day 1 of 
All 
Cycles 
(Pre-
dose)a 
Every 30 
Minutes 
During 
Mirvetuxima
b 
Soravtansine 
Infusionb,c 
Immediately 
After 
Completion 
of 
Mirvetuxima
b 
Soravtansin
e Infusiond 
4 Hours 
After End of 
Mirvetuxima
b 
Soravtansine 
Infusionc 
At 
Same 
Time 
as ECG 
Assess
-
mentse 
End of 
Treatmen
t and 
Follow-
up Visits 
Blood 
pressure 
● 
● 
● 
● 
● 
● 
● 
Pulse 
● 
● 
● 
● 
● 
● 
● 
Respiratory 
rate 
● 
● 
● 
● 
● 
● 
● 
Temperatu
re 
● 
● 
● 
● 
● 
 
● 
a Within 10 minutes before the start of infusion of mirvetuximab soravtansine. 
b ± 10 minutes. 
c Cycle 1 only. If the patient’s infusion was well tolerated, the 4-hour post–mirvetuximab soravtansine 
infusion assessment will not be required in Cycles ≥ 2. 
d Within 10 minutes after completion of infusion of mirvetuximab soravtansine. 
e Measured pre-dose and within 10 minutes after completion of each set of triplicate ECG readings (pre-
dose, end of mirvetuximab soravtansine infusion) to coincide with Cmax PK draw (+ 1 hour window), end 
of combination drug infusion to coincide with Cmax PK draw (+ 1 hour window), and 24 hours post-
infusion (± 2 hours); see also Section 8.7. Cycles 1 and 3 only. 
8.7. 
Electrocardiogram 
A standard, single 12-lead ECG will be performed within 14 days before Cycle 1 Day 1 to 
determine study eligibility.  
Triplicate ECGs will be performed at 2- to 5-minute intervals. A single ECG will also be 
performed at the end of treatment visit and as clinically indicated (Appendix A, Appendix B, and 
Appendix C). 
Vital signs (blood pressure, pulse, and respiratory rate) will be measured within 10 minutes of 
completion of each set of triplicate ECG readings. 
8.8. 
Pulse Oximetry 
Pulse oximetry will be performed at screening, before dosing on Day 1 of every cycle, and as 
indicated in Appendix A, Appendix B, and Appendix C. 
8.9. 
Pulmonary Function Tests 
Pulmonary function tests will be performed at screening and in the event of pulmonary 
symptoms as clinically indicated (Appendix A, Appendix B, and Appendix C). 
8.10. 
Laboratory Assessments 
Patients should be in a seated or supine position during blood collection. Screening labs and any 
required repeat testing will be performed as outlined in the Schedule of Clinical Assessments 
(Appendix A, Appendix B, and Appendix C) and as clinically indicated.  
Note that before each administration of mirvetuximab soravtansine, laboratory results must be 
reviewed to evaluate potential toxicity.  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
106 
8.10.1. 
Clinical Laboratory Panels 
A list of clinical laboratory tests is presented in Table 27. 
Table 27: 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Coagulation Tests 
Urinalysisa 
• 
Hematocrit 
• 
Hemoglobin 
• 
WBC (with 5-part 
differential) 
• 
RBC 
• 
Platelet count 
• 
Albumin 
• 
Alkaline phosphatase 
• 
ALT 
• 
AST 
• 
BUN 
• 
Calcium 
• 
Carbon dioxide 
• 
Chloride 
• 
Creatinine 
• 
Glucose 
• 
LDH 
• 
Magnesium 
• 
Phosphorus 
• 
Potassium  
• 
Sodium 
• 
Total bilirubin 
• 
Thyroid panel (Regimen D 
only)b 
• 
PT 
• 
aPTT 
• 
INR 
• 
pH 
• 
Ketones 
• 
Protein 
• 
Glucose 
• 
Occult blood 
• 
Leukocyte 
• 
esterase 
• 
Nitrite 
(Microscopic 
examination of 
sediment will be 
performed only if 
results of urinalysis 
dipstick are positive.) 
a For patients receiving bevacizumab, results from urinalysis should be available before dosing because of the 
increased risk of proteinuria. The test can be performed up to 48 hours before dosing. If the test result is +2, 
bevacizumab should be held until a 24-hour urine test is performed.  
b Thyroid panel should include T3 or free T3, free T4, and TSH; performed every 6 weeks. 
BUN, blood urea nitrogen; GFR, glomerular filtration rate; LDH, lactic acid dehydrogenase; RBC, red blood cell count; 
WBC, white blood cell count. 
8.11. 
Pregnancy Screen 
All female patients of childbearing potential will complete a serum beta-human chorionic 
gonadotropin or urine pregnancy test (not more than 3 days before the first dose of mirvetuximab 
soravtansine); this test must be negative for the patient to be enrolled and to receive the study 
drug. 
If a female patient becomes pregnant or suspects pregnancy while participating in this study, the 
Investigator and Sponsor must be informed immediately, and the patient will be withdrawn from 
study treatment. 
8.12. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group PS (Appendix E) will be assessed during screening and at 
other times specified in the Schedule of Clinical Assessments (Appendix A, Appendix B, and 
Appendix C). An assessment is not necessary on Day 1 of Cycle 1 if the screening assessment 
was obtained within 3 days before Day 1. 
8.13. 
Radiologic Imaging 
Radiologic tumor evaluation by CT scan or MRI of chest, abdomen, and pelvis will be 
performed within 28 days before the first dose and at other time points specified in the Clinical 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
107 
Schedule of Assessments (Appendix A, Appendix B, and Appendix C). The same radiologic 
assessment used at screening must be used at all subsequent radiologic evaluations.  
8.14. 
Echocardiogram/Multigated Acquisition Scan  
Echocardiograms or MUGA scans will be performed only in patients receiving pegylated 
liposomal doxorubicin (Regimen C, Appendix B). Echocardiograms or MUGA scans will be 
performed at screening and every four cycles of treatment or as medically indicated. The same 
test should be performed throughout the trial. If the patient’s left ventricular ejection fraction 
drops below normal or by at least 15% from the baseline value, treatment with pegylated 
liposomal doxorubicin should be stopped. 
8.15. 
Tumor Response Assessment 
8.15.1. 
RECIST and CA125 
Tumor response for patients with measurable lesions should be assessed using RECIST 
Version 1.1 (Eisenhauer 2009, Appendix G). Patients with ovarian cancer will have CA125 
measured every cycle and at approximately the same time that they undergo radiologic 
assessment. Patients will have a baseline tumor assessment done within 28 days before Cycle 1 
Day 1 and CA125 measured 14 days before Cycle 1 Day 1. Patients with measurable lesions 
should be assessed using CT scan or MRI approximately every second cycle, from the date of the 
first dose. For Regimens A, D, and E, this will continue through Week 24, and then scans will be 
performed every 3 months for up to 1 year from randomization, and then either every 6 months 
or per standard of care on the basis of symptoms until the 30-day follow-up visit. For 
Regimen C, the scan frequency will change 1 year after randomization to every 16 weeks or as 
clinically indicated. Although progression may be determined by the Investigator on the basis of 
clinical deterioration, every effort should be made to document progression using radiologic 
methods. The basis for determination of progression per clinical deterioration should be 
documented.  
Patients experiencing CA125 response must have a confirmatory test performed as detailed in 
the Clinical Schedule of Assessments (Appendix A, Appendix B, and Appendix C). In the case 
of stable disease (SD), follow-up measurements must have met the SD criteria at least once after 
study entry at a minimum interval of 6 weeks. 
The site is expected to maintain a copy of digital data for the retention period applicable to the 
protocol, Good Clinical Practice (GCP), and federal, international, and/or state legal and medical 
requirements.  
Note: It is very important that the same method of radiologic assessment be used 
throughout the study and that the same lesions are followed.  
8.15.2. 
Immune-Related RECIST (Regimen D Only) 
RECIST Version 1.1 will be adapted to account for the unique tumor response characteristics 
seen with treatment with pembrolizumab. Immunotherapeutic agents such as pembrolizumab 
may produce anti-tumor effects by potentiating endogenous cancer-specific immune responses. 
The response patterns seen with such an approach may extend beyond the typical time course of 
responses seen with cytotoxic agents, and can manifest a clinical response after an initial 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
108 
increase in tumor burden or even the appearance of new lesions. Standard RECIST may not 
provide an accurate response assessment of immunotherapeutic agents such as pembrolizumab. 
Therefore, RECIST Version 1.1 will be used with the adaptions outlined in Appendix I. These 
assessments will be performed on the scans performed for the RECIST assessment (see 
Section 8.15.1). 
Note: It is very important that the same method of radiologic assessment be used 
throughout the study and that the same lesions are followed.  
8.16. 
Eligibility Based on FRα Expression  
Instructions regarding processing and shipment of biopsy samples and archival tissues are 
detailed in the Laboratory Manual. Tumor samples will be analyzed for FRα expression in the 
Companion Diagnostics Pharma Services CAP-accredited and CLIA-certified laboratory and 
Pathology Services at Ventana Medical Systems, Inc. Samples from patients on Regimens A 
(Cohorts 1 and 2), B, and C will have their FRα levels assessed using the FOLR1-RPA assay. 
Samples from patients on Regimens A (Cohort 3), D, and E will have their FRα levels assessed 
using the FOLR1-IUO assay. 
All patients must have documented expression of FRα by IHC (≥ 25% or ≥ 50% [Protocol 
Amendment 4] of tumor staining at ≥ 2+ intensity) before enrollment. Immunohistochemistry 
may be performed on archival tissue to determine eligibility. If archival tissue is not available, 
then a new tumor biopsy must be obtained. De-identified pathology reports should be included 
with sample shipment to ImmunoGen or designee. In Study 0401, the FIH monotherapy study, 
most patients (98%) had available archival tissue.  
8.17. 
Biopsy of Tumor (Regimen D Only) 
A biopsy of tumor tissue will be performed on two occasions: The first biopsy will be performed 
before the first dose of any study treatment, and the second biopsy will be performed on Cycle 2 
Day 8 (± 3) (Section 7.1.1). Instructions regarding processing and shipment of the biopsy sample 
are detailed in the Laboratory Manual. 
9. 
ASSESSMENT OF SAFETY 
9.1. 
Recording Adverse Events  
Adverse events, including those attributed to study procedures, will be documented on the AE 
eCRF and monitored continuously throughout the study from the time of informed consent until 
30 days after the patient’s last study treatment. 
However, those AEs that meet seriousness criteria (ie, SAEs) will be followed up by 
ImmunoGen Pharmacovigilance until resolution, stabilization, or return to baseline. Beyond this 
defined reporting period, any unsolicited SAE assessed as related to the study drug by the 
Investigator and reported to ImmunoGen will be collected and processed. Additional information 
obtained after database lock will reside solely in the safety database.  
The frequency of AE monitoring increases for patients who experience a DLT, and for patients 
who discontinue study treatment because of a study-related AE, the reporting time period may be 
extended. These patients must be followed at least once a week for 4 weeks, and subsequently at 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
109 
4-week intervals until resolution, stabilization, or chronic state of the AE or laboratory 
abnormality, whichever comes first (Section 5.10.2). 
To ensure the safety of the patient, the Investigator should take appropriate measures to follow 
and provide updates for all AEs until clinical recovery is complete, laboratory values return to 
normal, the patient stabilizes, or death occurs. This may mean that observations continue beyond 
the last planned visit per protocol and that additional investigations may be requested by the 
Sponsor. 
9.1.1. 
Definition of Adverse Events 
9.1.1.1. 
Adverse Event  
An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or 
metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in 
any phase of a clinical study, whether or not considered study drug related. This includes an 
exacerbation of a pre-existing condition. Adverse events include: 
• Worsening (change in nature, severity, or frequency) of conditions present at the 
onset of the study 
• Drug-drug interactions 
• Events related to or possibly related to concomitant medications 
• Clinically significant abnormalities in physical examination, vital signs, and weight 
Adverse events may be discovered through observation or examination of the patient, 
questioning of the patient, complaint by the patient, or by abnormal clinical laboratory values. 
In addition, AEs may include laboratory values that become significantly out of range. Such 
abnormal laboratory values or test results constitute AEs if they induce clinical signs or 
symptoms, are considered clinically significant (eg, causes study discontinuation or constitutes in 
and of itself an SAE), or require therapy (eg, any hematologic abnormality that requires 
transfusion or growth factor treatment), and should be recorded on the AE eCRF under the signs, 
symptoms, or diagnosis associated with them. In the event of an out-of-range laboratory value, 
the laboratory test should be repeated until it returns to normal or baseline or can be explained 
and the patient’s safety is not at risk.  
9.1.1.2. 
Serious Adverse Event  
An SAE is any AE occurring at any dose that results in any of the following outcomes: 
• Death 
• Is life-threatening 
• Requires inpatient hospitalization 
• Requires prolongation of existing hospitalization 
• A persistent or significant disability or incapacity or substantial disruption of the 
ability to conduct normal life functions 
• A congenital anomaly or birth defect 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
110 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, and blood dyscrasias or convulsions that do not result in 
inpatient hospitalization. 
Note that hospitalization is defined as an admission to treat a clinical AE. The following events 
would not be considered hospitalizations for SAE-reporting purposes: 23-hour hold for 
observation, admission to a hospice facility or nursing home, respite care, outpatient surgery, 
social admission (eg, a homeless patient), or admission not associated with a precipitating 
clinical AE (eg, elective or pre-planned surgery or in-patient administration of subsequent 
chemotherapy). 
9.1.1.3. 
Adverse Events of Special Interest 
An adverse event of special interest (AESI) (serious or non-serious) is one of scientific and 
medical concern specific to the Sponsor’s product for which ongoing monitoring and rapid 
communication by the Investigator to the Sponsor is appropriate.  
All AESIs should be promptly reported per Section 9.2.1. 
9.1.1.4. 
Mirvetuximab Soravtansine  
Mirvetuximab soravtansine has one AESI, which is pneumonitis. 
Radiologic findings suggestive of pneumonitis include new onset of any of the following: 
• Pulmonary consolidation 
• Pulmonary infiltrate 
• Reticular infiltrate 
• Nodular infiltrate 
• Reticulo-nodular infiltrate 
• Ground-glass pulmonary infiltrate 
• Increased interstitial markings 
• Interstitial infiltrate 
• Honeycomb appearance 
9.1.1.5. 
Pembrolizumab 
Pembrolizumab has two AESIs: 
• An overdose of pembrolizumab, as defined in Section 5.14.  
• An elevated AST or ALT lab value that is ≥ 3 times the ULN and an elevated total 
bilirubin lab value that is ≥ 2 times the ULN and, at the same time, an alkaline 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
111 
phosphatase lab value that is less than 2 times the ULN, as determined by way of 
protocol-specified laboratory testing or unscheduled laboratory testing.* 
*Note that these criteria are based upon available regulatory guidance documents. The purpose 
of the criteria is to specify a threshold of abnormal hepatic tests that may require additional 
evaluation for an underlying etiology. The trial site guidance for assessment and follow-up of 
these criteria can be found in the Study Manual (or equivalent). 
9.1.2. 
Classification of Adverse Events 
All AEs will be evaluated according to the NCI CTCAE Version 4.03 (effective 14 June 2010) 
Appendix M. If the AE is not listed in the NCI CTCAE, it should be graded on the basis of the 
description given in Table 28. 
Table 28: 
Adverse Event Severity 
Severity 
Definition 
Grade 1 (mild) 
No limitation of usual activities 
Grade 2 (moderate) 
Some limitation of usual activities 
Grade 3 (severe) 
Inability to carry out usual activities 
Grade 4 (life-threatening) 
Immediate risk of death 
Grade 5 (fatal) 
Resulting in death 
Relationship of an AE or SAE to study drug(s) is to be determined by the Investigator on the 
basis of the definitions listed in Table 29. Relationship should be attributed not only to the 
combination Regimen, but also to each drug within the combination Regimen. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
112 
Table 29: 
Adverse Event Casual Relationship to Study Drug 
Relationship to Study 
Drug(s) 
Definition 
Not related 
No relationship between the event, including laboratory test 
abnormality, and the administration of study drug. There is no temporal 
relationship, and there is unambiguous evidence supporting another 
cause. 
Unlikely related 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to study drug administration that makes a causal 
relationship improbable, and in which other drugs, chemicals, or 
underlying disease provide plausible explanations.  
Possibly related 
A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to administration of study drug, but which could also be 
explained by concurrent disease or other drugs or chemicals. 
Information on study drug withdrawal may be lacking or unclear.  
Probably related 
A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to administration of study drug, unlikely to be attributed 
to concurrent disease or other drugs or chemicals, and which follows a 
clinically reasonable response on withdrawal (de-challenge). 
Re-challenge information is not required to fulfill this definition. The 
association of the clinical event, including laboratory test abnormality, 
must also have some biologic plausibility, at least on theoretical 
grounds. 
Definitely related 
A clinical event, including laboratory test abnormality, occurring in a 
plausible time relationship to study drug administration, and which 
cannot be explained by concurrent disease or other drugs or chemicals. 
The response to withdrawal of the study drug (de-challenge) should be 
clinically plausible.  
9.2. 
Reporting of Adverse Events 
9.2.1. 
Reporting of Serious Adverse Events and/or Adverse Events of Special Interest 
Any SAE or AESI, regardless of relationship to study medications, that occurs in a patient from 
the time of informed consent until 30 days after the last study treatment of mirvetuximab 
soravtansine, bevacizumab, carboplatin, and pegylated liposomal doxorubicin and 90 days after 
last treatment of pembrolizumab or 30 days following cessation of pembrolizumab if the patient 
initiates new anticancer therapy, whichever is earlier, must be recorded by the clinical site on an 
SAE Report Form. The event must also be recorded on the patient’s AE eCRF, including the 
Investigator’s assessment of the relationship of the event to the study treatment (mirvetuximab 
soravtansine and bevacizumab, pegylated liposomal doxorubicin, carboplatin, or 
pembrolizumab). The Investigator will promptly supply all information requested by the Sponsor 
(or Contract Research Organization [CRO]) regarding the event.  
The Investigator must submit the SAE Report Form to ImmunoGen Pharmacovigilance (or 
designee). This form must be completed and submitted within 24 hours after the Investigator 
learns of the event, using the contact information printed on the SAE Report Form and contained 
within the SAE Report Form Completion Guidelines. Follow-up information must be submitted 
using a new SAE Report Form. 
When reporting SAEs, the following additional points should be noted:  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
113 
• The underlying diagnosis or syndrome should be reported as the primary SAE term, 
rather than the signs or symptoms (signs and symptoms may be described in the 
narrative). 
• An event term of “Death” should not be used, but rather should be recorded as an 
outcome of a specific SAE term. Initially, the event term of “death NOS” (not 
otherwise specified) can be used until the actual cause of death is known. If an 
autopsy was performed, the autopsy report should be provided. 
When reporting AESIs, the following additional points should be noted: 
• As described in Section 9.1.1.3, serious or non-serious events, any symptom, or sign 
potentially suggestive of an AESI must be promptly reported on an SAE Report 
Form. Please refer to the SAE Completion Guidelines and SAE Report Form for 
additional information. 
It is the responsibility of the Sponsor to ensure that each Investigator receives a copy of any 
suspected unexpected serious adverse reaction (SUSAR) report (Council for International 
Organizations of Medical Sciences [CIOMS]/MedWatch report) regarding the study drug(s) and 
as submitted to the appropriate national regulatory agencies.  
The Investigator (or Sponsor or designee) must promptly report all SUSARs to the IRB/IEC for 
review in accordance with national regulations. The IRB/IEC notification of the SUSAR may be 
a submission of a copy of the CIOMS/MedWatch report or other format accepted by the 
IRB/IEC. A copy of the CIOMS/MedWatch report and notification to the IRB/IEC should be 
retained in the site’s Investigator Site File.  
In addition to the CIOMS/MedWatch reports, the Sponsor will notify (through annual update to 
the Investigator Brochure) the Investigators and IRBs/IECs of all deaths that occur during the 
study, irrespective of relationship to study drug(s). 
9.2.2. 
Reporting of Disease Progression 
Disease progression and/or progression of the disease under study is an anticipated occurrence in 
oncology drug development and is part of the efficacy objectives of this study. It is not an AE 
per se and should not be used as an AE term.  
However, any medical event or condition that is untoward in the context of PD and/or for the 
specific patient’s disease course should be reported as an AE and assessed accordingly by the 
Investigator.  
Progression of disease with a fatal outcome does not need to be reported as an AE term. 
However, the applicable protocol eCRF page(s) pertaining to death must be completed 
immediately to record the PD/death. 
9.2.3. 
Reporting a Pregnancy 
Pregnancy and lactation are exclusion criteria for this study. A WCBP, defined as a sexually 
mature woman who has not undergone surgical sterilization or who has not been naturally post-
menopausal for at least 12 consecutive months (ie, who has had menses any time in the 
preceding 12 consecutive months) must agree to use effective contraceptive methods while on 
study treatment and for the following time periods: 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
114 
• At least 12 weeks after the last dose of mirvetuximab soravtansine 
• At least 6 months after the last dose of bevacizumab, carboplatin, or pegylated 
liposomal doxorubicin 
• At least 4 months after the last dose of pembrolizumab 
The Sponsor must be notified immediately in the event of a pregnancy occurring during the 
course of the study and through the following time periods: 
• 30 days after a patient’s last dose of mirvetuximab soravtansine, bevacizumab, 
carboplatin, or pegylated liposomal doxorubicin 
• 120 days after cessation of pembrolizumab or 30 days after cessation of treatment if 
the subject initiates new anticancer therapy, whichever is earlier 
Pregnancy is not an AE unto itself and therefore should not be reported as an AE. 
All pregnancies will be recorded on a Pregnancy Report Form and submitted according to the 
contact information on the form and the form completion guidelines.  
Pregnancies, with the permission of the mother, will be followed to completion or termination 
using the designated sections of the Pregnancy Report Form.  
Any SAE occurring during the pregnancy, to the mother or fetus, requires that a SAE Report 
Form also be submitted. 
10. 
STUDY ACTIVITIES 
All study visits and assessments that must be performed during the study and follow-up are 
included in Appendix A, Appendix B, and Appendix C. 
10.1. 
Screening Visit 
The Investigator is responsible for keeping a record of all patients screened for entry into the 
study and subsequently excluded. The reason(s) for exclusion must also be recorded. The 
screening procedures must be performed within 28 days before Day 1, unless otherwise 
specified.  
10.1.1. 
Standard of Care Assessments 
In some cases, clinical assessments performed before obtaining informed consent may be used to 
qualify the patient for the study. These include radiologic tumor assessment, physical 
examinations, hematology, serum chemistry results, coagulation studies, urinalysis, or other 
assessments that may be considered part of the normal standard of care. In these cases, repeat 
assessments may not be necessary before enrollment, unless individual parameters require 
further study or confirmation and are clinically appropriate. 
10.2. 
End of Treatment Visit 
Patients may voluntarily withdraw from the study treatment at any time for any reason, and 
without prejudice to further treatment. In addition, patients may be withdrawn by the Investigator 
if the Investigator does not feel that the patient is deriving clinical benefit or because the patient 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
115 
is experiencing unacceptable toxicity. The reasons for which a patient may be prematurely 
discontinued are listed in Section 5.10.5.  
Patients who withdraw or are removed from the study treatment will have an end of treatment 
visit within 7 days after the decision to discontinue study treatment. Additionally, these patients 
will undergo a 30-day follow-up safety visit. The eCRF will capture reasons for withdrawal.  
10.3. 
Follow-up Assessments 
10.3.1. 
Safety Follow-up 
A safety follow-up visit will occur 30 days (+ 14 days) after the last treatment.  
All SAEs, and those AEs assessed by the Investigator as at least possibly related to study drug, 
should continue to be followed until they resolve or stabilize, whichever comes first. Reporting 
of SAEs is detailed in Section 9.2.1. 
10.3.2. 
Response Follow-up 
Patients who have discontinued study treatment for reasons other than PD will be followed per 
RECIST Version 1.1 (Appendix G) every 12 weeks (± 3 weeks) until documentation of PD or 
until the patient starts subsequent anti-cancer therapy, whichever comes first.  
11. 
STATISTICAL METHODS 
All statistical analyses will be performed using the most recent release of SAS statistical 
software, unless otherwise noted. For categorical variables, the number (n) and percentage of 
each category within a parameter will be presented. For continuous variables, the sample size 
(n), mean, median, standard deviation, and the minimum and maximum values will be presented. 
Missing data will not be imputed unless otherwise stated. There will be a detailed description of 
patient disposition, patient demographics, and baseline characteristics. 
No formal interim analysis is planned for this study. However, a review of safety data and 
available preliminary PK data will be conducted by the CRC after the MTD or an RP2D for each 
combination Regimen has been determined. Results from this data review could enable dose 
selection for additional studies with mirvetuximab soravtansine, before the completion of this 
study. 
A statistical analysis plan will fully describe the planned analyses for this trial and will be 
finalized before database lock. All analyses will be performed for any patient who receives study 
drug. All analyses for anti-tumor activity will use Cycle 1 Day 1 as the start time. 
11.1. 
Sample Size 
Ascending doses of mirvetuximab soravtansine and bevacizumab, carboplatin, pegylated 
liposomal doxorubicin, or pembrolizumab are to be evaluated to identify the MTD for each of 
the four doublet combination Regimens. The actual number of patients accrued during the Dose 
Escalation phase will be determined largely by the findings observed during the course of their 
treatment. Regimen A (mirvetuximab soravtansine + bevacizumab) is expected to enroll 
16 patients, whereas Regimen B (mirvetuximab soravtansine + carboplatin) and Regimen C 
(mirvetuximab soravtansine + pegylated liposomal doxorubicin) are expected to enroll 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
116 
22 patients. Regimen D (mirvetuximab soravtansine + pembrolizumab) is expected to enroll 
16 patients. For all four Regimens, up to 10 additional patients will be treated at the MTD.  
Overall, the Dose Escalation phase of the study is expected to enroll approximately 76 to 
120 patients. 
Following MTD determination, there will be a Dose Expansion phase for Regimen A 
(mirvetuximab soravtansine + bevacizumab) and Regimen D (mirvetuximab soravtansine + 
pembrolizumab).  
Regimen A (Mirvetuximab Soravtansine + Bevacizumab) 
Patients enrolled in the Dose Expansion phase will be allocated to three Dose Expansion Cohorts 
according to prior exposure to bevacizumab as follows: 1) Dose Expansion Cohort 1: 
bevacizumab naïve; 2) Dose expansion Cohort 2: bevacizumab pre-treated; and 3) Dose 
Expansion Cohort 3: with one to three prior therapies including one prior therapy with 
bevacizumab (per Protocol Amendment 5).  
For the bevacizumab-naïve Cohort (Cohort 1), assuming a response rate of 55%, there is a 94.2% 
probability of detecting at least 8 responders if 20 patients are recruited. The response rate 
assumption is based on an ORR of 53% observed with the standard of care therapy of paclitaxel 
in combination with bevacizumab in patients with platinum-resistant EOC 
(Bevacizumab [package insert] 2014). 
For the bevacizumab-pretreated Cohort (Cohort 2), assuming a response rate of 50%, there is a 
91.2% probability of detecting at least 14 responders if 35 patients are recruited.  
For the bevacizumab expansion (Cohort 3), assuming a response rate of 50%, there is a 95.4% 
probability of detecting at least 24 responders if 60 patients are recruited. In addition, the 90% 
confidence interval for true ORR is given in the table below if the observed number of 
responders is 20 to 40 of 60 patients.  
Responses Observed, 60 Patients 
90% Exact Confidence Interval for True ORR 
20/60 (33%) 
(23%, 45%) 
21/60 (35%) 
(25%, 46%) 
22/60 (37%) 
(26%, 48%) 
23/60 (38%) 
(28%, 50%) 
24/60 (40%) 
(29%, 51%) 
25/60 (42%) 
(31%, 53%) 
26/60 (43%) 
(32%, 55%) 
27/60 (45%) 
(34%, 56%) 
28/60 (47%) 
(36%, 58%) 
29/60 (48%) 
(37%, 60%) 
30/60 (50%) 
(39%, 61%) 
31/60 (52%) 
(40%, 63%) 
32/60 (53%) 
(42%, 64%) 
33/60 (55%) 
(44%, 66%) 
34/60 (57%) 
(45%, 68%) 
35/60 (58%) 
(47%, 69%) 
36/60 (60%) 
(49%, 71%) 
37/60 (62%) 
(50%, 72%) 
38/60 (63%) 
(52%, 74%) 
39/60 (65%) 
(54%, 75%) 
40/60 (67%) 
(55%, 77%) 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
117 
Regimen D (Mirvetuximab Soravtansine + Pembrolizumab) 
In the Dose Expansion phase for Regimen D, a total of 35 patients will be enrolled at FRα > 50% 
of tumor staining at intensity ≥ 2+ and 11 patients with a FRα 25% to 49% of tumor staining at 
intensity ≥ 2+. Assuming a response rate of 50%, there is a 91.2% probability of detecting at 
least 14 responders if 35 patients are recruited. In addition, the 90% confidence interval for true 
ORR is given in the table below if the observed number of responders is 12 to 18 of 35 patients. 
Responses Observed, 35 Patients 
90% Exact Confidence Interval for True ORR 
12/35 (34%) 
(21%, 50%) 
13/35 (37%) 
(24%, 52%) 
14/35 (40%) 
(26%, 55%) 
15/35 (43%) 
(29%, 58%) 
16/35 (46%) 
(31%, 61%) 
17/35 (49%) 
(34%, 64%) 
18/35 (51%) 
(36%, 66%) 
Regimen E (Mirvetuximab Soravtansine + Bevacizumab + Carboplatin) 
In Regimen E (Triplet), approximately 50 patients will be enrolled to ensure that 40 patients will 
be treated at the MTD. Assuming a response rate of 60%, there is a 92.6% probability of 
detecting at least 20 responders if 40 patients are recruited. In addition, the 90% confidence 
interval for true ORR is given in the table below if the observed number of responders is 20 to 
26 of 40 patients.  
Responses Observed, 40 Patients 
90% Exact Confidence Interval for True ORR 
20/40 (50%) 
(36%, 64%) 
21/40 (52.5%) 
(38%, 66%) 
22/40 (55%) 
(41%, 69%) 
23/40 (57.5%) 
(43%, 71%) 
24/40 (60%) 
(46%, 73%) 
25/40 (62.5%) 
(48%, 75%) 
26/40 (65%) 
(51%, 77%) 
Overall, the Dose Expansion phase is expected to enroll up to 211 patients. Assuming that 
approximately 90% of enrolled patients in the Dose Expansion phase will be evaluable, the study 
is expected to accrue approximately 311 to 355 patients.  
Safety will be evaluated continuously, separately, and in aggregate in the expansion Regimens. If 
at any time ≥ 33% of patients treated in an expansion Regimen experience a Cycle 1 DLT, 
further enrollment to that Cohort will stop, and the CRC will be convened. The CRC will review 
all available safety and PK data to determine how further dosing should proceed. If the CRC 
determines that the dose should be revised during the expansion phase for a given expansion 
Cohort, that Cohort will enroll additional patients at the revised dose to fulfill the enrollment 
goal.  
11.2. 
Pharmacokinetic Analyses 
Pharmacokinetic parameters, if feasible, will be derived from plasma concentrations of 
mirvetuximab soravtansine total antibody, DM4, and S-methyl DM4 using the actual sampling 
times and non-compartmental methods. Plasma concentration data and PK parameters will be 
summarized by cohort, cycle, and dose level as appropriate.  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
118 
Plasma or serum concentrations for pegylated liposomal doxorubicin, bevacizumab, carboplatin, 
and pembrolizumab will summarized by cohort, cycle, and dose level as appropriate.  
Individual and mean (standard deviation) plasma concentration-time profiles will be presented 
graphically by cohort, cycle, and dose level as appropriate. 
11.3. 
Immunogenicity Assessment 
The percentage of patients who screen positive for ADA, the percentage of patients who are 
confirmed positive, and antibody titer data will be summarized by cohort and time point using 
descriptive statistics. The potential impact of immunogenicity against mirvetuximab soravtansine 
on PK, safety, and anti-tumor activity will be explored.  
11.4. 
Safety Analyses 
Adverse events, concomitant medications, and results from physical examinations will be listed.  
Adverse events will also be coded with the Medical Dictionary for Regulatory Activities 
(MedDRA; Version 18.0 or later) and summarized by System Organ Class and Preferred Term. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
(WHO-DD; 01 June 2012 or later version). A dictionary listing of all unique concomitant 
medications used in the study will be provided. 
All hematology, blood chemistry, vital signs, and ECG results will be listed by patient for each 
assessment, and descriptive statistics will be tabulated for select criteria. Changes from baseline 
in hematology, blood chemistry, vital signs, ECHO/MUGA scan (Regimen C), and ECG results 
will be summarized by treatment. Shifts in hematology and blood chemistry from baseline values 
will be summarized. Plasma also will be evaluated for the presence of humoral responses against 
the M9346A antibody component or against the DM4 component (ADA).  
11.5. 
Anti-tumor Activity 
Objective Response Rate 
The best objective response will be determined by the Investigator for each patient as either CR, 
PR, SD, or relapsed disease/PD using RECIST Version 1.1, CA125, and irRECIST Version 1.1 
(Regimen D) evaluations (see Appendix G, Appendix H, and Appendix I). Confirmed objective 
responses for patients in the Dose Escalation phase will be summarized by dose assigned and the 
dose at which the response occurred. For the Dose Expansion phase, responses will be reported 
overall and separately for each expansion Cohort. Response rate will be calculated as the number 
of CRs or PRs divided by the number of response-evaluable patients. To meet the definition of 
response evaluable, patients must have undergone radiologic assessment at baseline, received at 
least one dose of combination treatment, and must have had at least one post-dose tumor 
assessment. 
Duration of Response 
Duration of response, defined as the time from initial response until PD, will be estimated for all 
patients who achieve a confirmed objective response (PR or CR) using the Kaplan-Meier 
method. Results will be summarized by dose cohort assigned and dose at which the response 
occurred. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
119 
Progression-Free Survival 
Progression-free survival, defined as the time from initiation of study drug until PD or death, 
whichever occurs first, will be estimated using the Kaplan-Meier method. The median PFS and 
PFS rate at 6 months will be presented. Results will be summarized by dose cohort. 
For DOR and PFS calculations, patients not achieving the endpoint will be censored at the time 
of the last endpoint assessment. Median response times and associated 95% confidence intervals 
will be presented.  
12. 
QUALITY CONTROL AND ASSURANCE 
Clinical sites will be monitored by ImmunoGen or its designee to ensure the accuracy of data 
against source documents. Data will be captured using validated electronic systems. Adverse 
events will be coded using MedDRA Version 18.0 or later. Concomitant medications will be 
coded using the WHO-DD 01 June 2012 or later version. Training will occur at an Investigator 
meeting or at the site initiation visit or both, and instruction manuals (eg, laboratory manuals and 
pharmacy manuals) will be provided to aid consistency in data collection and reporting across 
sites. 
All required data will be entered into the clinical and/or safety database in accordance with Code 
of Federal Regulations (CFR) 21 Part 11 and International Conference on Harmonisation (ICH) 
E6. The database will include an audit trail to document all data processing and activity on each 
data field by each user. Users will be given restricted access according to their role in the study 
through a password-protected environment. All missing data will be explained. 
Data entered in the system must be verifiable against source documents and will be reviewed 
manually for validity and completeness against the source documents by a clinical monitor from 
ImmunoGen or its designee. If necessary, the study site will be contacted for corrections or 
clarifications. 
13. 
ADMINISTRATIVE CONSIDERATIONS, STUDY MONITORING, AND 
DATA MANAGEMENT 
13.1. 
Investigators and Study Administrative Structure 
Before initiation of the study, the Investigators must provide the Sponsor with a completed 
Form FDA 1572. Study medications may be administered only under the supervision of the 
Investigators listed on this form. Curricula vitae must be provided for the Investigators and sub-
Investigators listed on Form FDA 1572. 
The Investigator should ensure that all persons assisting with the study are qualified and trained 
before performing delegated study-related duties. The Investigator must maintain a list of site 
personnel to whom he or she has delegated significant study-related duties. 
13.2. 
Institutional Review Board or Independent Ethics Committee Approval 
Before initiation of the study, the Investigator must provide the Sponsor with a copy of the 
written IRB/IEC approval of the protocol, the study ICF, and the screening ICF (the latter ICF is 
applicable for sites requesting permission to pre-screen for FRα positivity before performing any 
additional study-related tests). This approval must refer to the ICF(s) and to the study title, study 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
120 
number, and version and date of issue of the study protocol, as given by the Sponsor on the title 
page of the protocol. 
Status reports must be submitted to the IRB/IEC at least once per year or per institutional 
guidelines. The IRB/IEC must be notified of study completion, and a final report must be 
provided to the IRB/IEC. A copy of these reports will be sent to the study clinical monitor or 
designee. The Investigators must maintain an accurate and complete record of all submissions 
made to the IRB/IEC, including a list of all reports and documents submitted. Adverse events 
that are subject to expedited reporting to the US FDA or other regulatory agencies (SUSARs) 
must be submitted promptly to the IRB/IEC. 
13.3. 
Ethical Conduct of the Study 
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor and Investigators abide by 
the Declaration of Helsinki; GCP as described in 21 CFR Parts 50, 56, and 312; and ICH GCP 
guidelines.  
13.4. 
Patient Information and Consent 
Before enrolling in the clinical study, the patient or the patient’s legally authorized 
representative(s) must sign an IRB/IEC-approved ICF to participate, after the nature, scope, and 
possible consequences of the clinical study have been explained in a form understandable to him 
or her. An IRB/IEC-approved ICF that includes information about the study will be prepared and 
given to the patient or the patient’s legally authorized representative(s). This document will 
contain all FDA, ICH, and IRB/IEC-required elements. The ICF must be in a language 
understandable to the patient or the patient’s legally authorized representative(s) and must 
specify who informed the patient or the patient’s legally authorized representative. 
After the patient has been given ample time to read and ask questions regarding the informed 
consent document and has been informed that participation is voluntary, the patient or the 
patient’s legally authorized representative(s) must give consent in writing. If the patient or the 
patient’s legally authorized representative(s) is unable to read, oral presentation and explanation 
of the written ICF and information to be supplied must take place in the presence of an impartial 
witness. Consent must be confirmed at the time of consent orally and by the personally dated 
signature of the patient or by the patient’s legally authorized representative(s). The witness and 
the person conducting the informed consent discussions must also sign and personally date the 
informed consent document. It should also be recorded and dated in the source document that 
consent was given. 
A copy of the signed and dated consent document(s) must be given to the patient or the patient’s 
legally authorized representative(s). The original signed and dated consent document will be 
retained by the Investigator. Patient confidentiality will be maintained as outlined in Section 13.5. 
The Investigator will not undertake any measures specifically required solely for the clinical 
study until valid consent has been obtained. 
A model of the full study ICF will be provided to the sites separately from this protocol.  
A screening ICF may be used to confirm a patient’s consent to analyze archived or new tumor 
samples for FRα expression. If the IHC screening assay is positive for FRα, the patient will be 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
121 
provided the full study consent, and only after signing the full study ICF will additional study-
specific screening tests be performed. A model of the screening ICF will be provided to the sites 
separately from this protocol. 
Participants must be re-consented to the most current version of the ICF(s) per IRB/IEC 
guidelines during their participation in the study. 
13.5. 
Patient Confidentiality 
Protected health information (eg, patient name) will not be collected and provided to the Sponsor 
and/or CRO. If protected health information appears on any documents, it must be redacted 
before a copy of the document is supplied to the Sponsor and/or CRO. Study findings stored on a 
computer will be stored in accordance with local data protection laws. Patient blood and tissue 
samples sent to outside laboratories and/or CROs (eg, IHC laboratory) are identified only by 
study patient number to ensure maintenance of confidentiality. The patient consent form will 
state that publications resulting from this study will not refer to patient names or include any 
other information that might disclose the identity of the patient. Patients will be told that 
representatives of the Sponsor, a designated CRO, the IRB/IEC, monitors, auditors, or regulatory 
authorities may inspect their medical records to verify the information collected, and that all 
personal information made available for monitoring, audit, or inspection will be handled in 
strictest confidence and in accordance with local data protection laws. The Investigator will 
maintain a personal patient identification list (patient numbers with the corresponding patient 
names) to enable records to be identified. 
13.6. 
Study Monitoring 
Monitoring procedures that comply with current GCP guidelines will be followed. On-site 
review of the case report forms (CRFs) for completeness and clarity, cross-checking with source 
documents, and clarification of administrative matters will be performed. 
The study will be monitored by the Sponsor or its designee. On-site monitoring will be 
performed by a representative of the Sponsor (Clinical Study Monitor) who will review the CRFs 
and source documents. The site monitor will ensure that the investigation is conducted according 
to protocol design and regulatory requirements by frequent site visits and communications 
(email, letter, telephone, and facsimile). 
13.7. 
Case Report Forms and Study Reports 
Case report forms (paper or electronic) are provided for each patient. All forms must be filled out 
by authorized study personnel. All corrections to the original CRF entry must indicate the reason 
for change. The Investigator is required to sign/e-sign the CRF after all data have been captured 
for each patient. If corrections are made after review and signature by the Investigator, the 
Investigator must be made aware of the changes, and his or her awareness documented by re-
signing the CRF. 
13.8. 
Critical Documents 
Before ImmunoGen initiates the study (ie, obtains informed consent from the first patient), it is 
the Investigator’s responsibility to ensure that the following documents are available to 
ImmunoGen or designee: 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
122 
• Curricula vitae of Investigator and sub-Investigator(s) (current, dated, and signed or 
supported by an official regulatory document) 
• Signed and dated agreement of the final protocol 
• Signed and dated agreement of any amendment(s), if applicable 
• Approval/favorable opinion from the IRB/IEC clearly identifying the document and 
document revision reviewed, including, but not limited to, the protocol, any protocol 
amendments, Investigator Brochure, Patient Information Form/ICF, and any other 
written information to be provided regarding patient recruitment procedures 
• Copy of IRB/IEC-approved Patient Information Form/ICF/any other written 
information/advertisement 
• List of IRB/IEC committee members/constitution or equivalent compliance statement 
• Study and financial agreement(s) 
• Completed Form FDA 1572 
• Completed Financial Disclosure Form 
Additional documents such as laboratory reference ranges and certifications will be collected 
during the study. Ongoing regulatory approvals and notifications as required must also be 
available; these are the responsibility of ImmunoGen. 
13.9. 
Protocol Violations/Deviations 
The Investigator will conduct the study in compliance with the protocol. The protocol will not be 
initiated until the IRB/IEC and the appropriate regulatory authorities have given approval/ 
favorable opinion. Modifications to the protocol will not be made without agreement of the 
Sponsor. Changes to the protocol will require written IRB/IEC approval/favorable opinion before 
implementation, except when the modification is needed to eliminate an immediate hazard(s) to 
patients. If applicable regulatory authorities permit, the IRB/IEC may provide expedited review 
and approval/favorable opinion for minor change(s) in ongoing studies that have the 
approval/favorable opinion of the IRB/IEC. The Sponsor will submit all protocol modifications 
to the regulatory authorities in accordance with the governing regulations. 
A record of patients screened but not entered into the study is also to be maintained.  
When immediate deviation from the protocol is required to eliminate an immediate hazard to 
patients, the Investigator will contact the Sponsor or its designee, if circumstances permit, to 
discuss the planned course of action. Any departures from the protocol must be fully documented 
as a protocol deviation. Protocol deviations will need to be reviewed by the Medical Monitor and 
may be required to be submitted to the IRB/IEC per institutional guidelines. 
Protocol modifications will be initiated only by the Sponsor and must be approved by the 
IRB/IEC and submitted to the US FDA or other applicable international regulatory authority 
before initiation. 
Prospective protocol waivers or exemptions are not permitted. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
123 
13.10. 
End of Study 
The end of the study will occur when either all patients have discontinued, all patients have been 
followed to progression, or 2 years after the last patient has been enrolled into the study, 
whichever occurs first. 
All patients who are actively enrolled in the study when the study ends will be given the 
opportunity to continue on study treatment until progression, either under this protocol or via a 
suitable rollover protocol. 
13.11. 
Study Termination 
13.11.1. 
Study Termination 
If the Sponsor, an Investigator, or Study Clinical Monitor discovers conditions arising during the 
study that indicate that the clinical investigation should be halted because of an unacceptable 
patient risk, the study must be terminated after appropriate consultation between ImmunoGen 
and the Investigators. In addition, a decision on the part of ImmunoGen to suspend or 
discontinue development of the test material may be made at any time.  
Within 15 days after premature closure, ImmunoGen must notify the competent authorities and 
IECs of any member state where the study is being conducted, providing the reasons for 
premature study closure. 
13.11.2. 
Site Termination 
A specific site may be terminated separate from the general study for conditions including, but 
not limited to, the following: 
• The discovery of an unexpected, significant, or unacceptable risk to the patients 
enrolled at the site 
• Failure of the Investigator to enter patients at an acceptable rate 
• Insufficient adherence by the Investigator to protocol requirements 
• Insufficient, incomplete, and/or unevaluable data 
13.12. 
Access to Source Documentation 
Regulatory authorities, the IEC/IRB, or the Sponsor may request access to all source documents, 
CRFs, and other study documentation for on-site audit or inspection. Direct access to these 
documents must be guaranteed by the Investigator, who must provide support at all times for 
these activities. Monitoring and auditing procedures that comply with current GCP guidelines 
will be followed. On-site review of the CRFs for completeness and clarity, cross-checking with 
source documents, and clarification of administrative matters will be performed. 
13.13. 
Data Generation and Analysis 
The clinical database will be developed and maintained by a CRO or an electronic data capture 
technology provider as designated by ImmunoGen. ImmunoGen or its designee will be 
responsible for performing study data management activities and analyses. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
124 
13.14. 
Retention of Data 
Essential documents should be retained until the following requirements are met: 
• A minimum of 2 years has elapsed following the last approval of a marketing 
application and there are no pending or contemplated marketing applications. 
Or 
• At least 2 years have elapsed since the formal discontinuation of clinical development 
of the investigational product. 
Or  
• The record retention policies and guidelines for countries in which the study is being 
conducted are followed (whichever is longer). 
It is the responsibility of the Sponsor to inform the Investigator or institution of when these 
documents no longer need to be retained. 
13.15. 
Financial Disclosure 
All investigators (eg, Investigator and sub-Investigators) will disclose any financial interests in 
the Sponsor as described in 21 CFR Part 54 before beginning this study and for 12 months after 
the study has completed. The appropriate form will be provided to the Investigator by the 
Sponsor, and the form will be signed and dated by the Investigator before the start of the study.  
All financial details relating to the Investigator’s participation in this study are provided in the 
separate contract between the institution and ImmunoGen. 
13.16. 
Publication and Disclosure Policy 
The information obtained during the conduct of this clinical study is confidential, and disclosure 
to third parties other than those noted below is prohibited. All information concerning the 
product and any matter concerning the operation of the Sponsor, such as clinical indications for 
the drug, its formula, methods of manufacture, and other scientific data relating to it, that have 
been provided by the Sponsor and are unpublished are confidential and must remain the sole 
property of the Sponsor. The Investigator will agree to use the information only for the purposes 
of carrying out this study and for no other purpose unless prior written permission from the 
Sponsor is obtained. 
Information obtained during the conduct of this study will be used by ImmunoGen in connection 
with the development of the study drug. The study Investigator is obliged to provide 
ImmunoGen with complete test results and all data developed in this study. The Sponsor has full 
ownership of the original CRFs completed as part of the study. This information may be 
disclosed to other physicians who are conducting similar studies and to health authorities as 
deemed necessary by the Sponsor. Patient-specific information may be provided to other 
appropriate medical personnel related to the care of that patient only with patient’s prior consent.  
The Investigator and any other clinical personnel associated with this study will not publish the 
results of the study, in whole or in part, at any time, unless they have consulted with 
ImmunoGen, provided ImmunoGen a copy of the draft document intended for publication, and 
obtained ImmunoGen’s written consent for such publication. All information obtained during the 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
125 
conduct of this study will be regarded as confidential. ImmunoGen will use the information for 
registration purposes and for the general development of the drug. 
14. 
LIST OF REFERENCES 
Ab O, Whiteman KR, Bartle LM, et al. IMGN853, a folate receptor-α (FRα)-targeting antibody-
drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors. Mol 
Cancer Ther. 2015;14(7):1605-1613. 
Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-
controlled phase II trial of chemotherapy with or without bevacizumab in patients with platinum-
sensitive recurrent epithelial ovarian, primary peritoneal or Fallopian tube cancer. J Clin Oncol. 
2012;30(17):2039-2045.  
Alkema NG, Wisman GB, van der Zee AG, van Vugt MA, de Jong S. Studying platinum 
sensitivity and resistance in high-grade serous ovarian cancer: Different models for different 
questions. Drug Resist Update. 2016;24:55-69.  
What Are the Risk Factors for Ovarian Cancer? American Cancer Society website. 
https://www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/risk-factors.html. 
Updated 04 February 2016. Accessed 08 May 2018. 
Ovarian, Fallopian Tube, and Peritoneal Cancer - Stages and Grades. American Society of 
Clinical Oncology (ASCO) website. https://www.cancer.net/cancer-types/ovarian-fallopian-tube-
and-peritoneal-cancer/stages-and-grades. Published October 2017. Accessed 08 May 2018. 
Armstrong DK. Topotecan dosing guidelines in ovarian cancer: reduction and management of 
hematologic toxicity. Oncologist. 2004;9(1):33-42. 
Basal E, Eghbali-Fatourechi GZ, Kalli KR, et al. Functional folate receptor alpha is elevated in 
the blood of ovarian cancer patients. PLoS One. 2009;4(7): e6292. 
Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology 
clinical practice guideline update. J Clin Oncol. 2011;29(31):4189-4198. 
Bergstrom J, Shih I-M, Fader AN. Chapter 10 - Updates on Rare Epithelial Ovarian Carcinoma. 
In: Birrer MJ and Ceppi L (Eds). Translational Advances in Gynecologic Cancers. London, 
United Kingdom: Academic Press, an Imprint of Elsevier: 2017:181-195.  
Bevacizumab [package insert]. South San Francisco, CA: Genentech, Inc.; 2014. 
Burger R, Brady M, Bookman M, et al. Incorporation of bevacizumab in the primary treatment 
of ovarian cancer. N Engl J Med. 2011;365: 2473-2483. 
Cancer Stat Facts: Ovarian Cancer. National Cancer Institute - SEER website. 
https://seer.cancer.gov/statfacts/html/ovary.html. Accessed 08 May 2018. 
Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with 
immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell 
stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004;173(2):945-
954. 
Chen YL, Chang MC, Huang CY, et al. Serous ovarian carcinoma patients with high alpha-folate 
receptor had reducing survival and cytotoxic chemo-response. Mol Oncol. 2012;6(3):360-369.  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
126 
Cobb LP, Gaillard S, Wang Y, Shih I-M, Secord AA. Adenocarcinoma of Mullerian origin: 
review of pathogenesis, molecular biology, and emerging treatment paradigms. Gynecol Oncol 
Res Pract. 2015;2:1. doi:10.1186/s40661-015-0008-z. 
Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel–carboplatin 
chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG 
Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, 
randomised, phase 3 trial. Lancet Oncol. 2017;18(6):779-791. 
Crane LMA, Arts JG, van Oosten M, et al. The effect of chemotherapy on expression of folate 
receptor-alpha in ovarian cancer. Cell Oncol (Dordr). 2012;35(1):9-18. 
Disis, Mary L. Immune regulation of cancer. J Clin Oncol. 2010;28(29):4531-4538. 
Dudley ME, Wunderlich JE, Yang JC, et al. Adoptive cell transfer therapy following non-
myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory 
metastatic melanoma. J Clin Oncol. 2005;23(10):2346-2357. 
Eisenhauer E, Therasse P, Bogaerts J, et al. New response criteria in solid tumors: Revised 
RECIST Guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 
Elnakat H, Ratnam M. Distribution, functionality and gene regulation of folate receptor 
isoforms: implications for targeted therapy. Adv Drug Deliv Rev. 2004;56(8):1067-1084. 
Ferrero JM, Wever B, Lepille D, et al. Carboplatin (PA) and pegylated liposomal doxorubicin 
(CA:PACA regimen) in patients with advanced ovarian cancer in late relapse (>6 months) 
(AOCLR): results of a GINECO phase II trial. J Clin Oncol. 2004;22(14 suppl):5022. 
Fisher RE, Siegel BA, Edell SL, et al. Exploratory study of 99mTc-EC20 imaging for identifying 
patients with folate-receptor positive solid tumors. J Nucl Med. 2008;49(6):899-906.  
Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. 
Immunol Rev. 2010;236:219-242. 
Garcia A, Singh H. Bevacizumab and ovarian cancer. Ther Adv Med Oncol. 2013;5(2):133-141. 
Garin-Chesa P, Campbell I, Saigo PE, Lewis JL Jr, Old LJ, Rettig WJ. Trophoblast and ovarian 
cancer antigen LK26, sensitivity and specificity in immunopathology and molecular 
identification as a folate binding protein. Am J Path. 1993;142(2):557-567. 
Gladieff L, Ferrero A, De Rauglaudre G, et al. Carboplatin and pegylated liposomal doxorubicin 
versus carboplatin and paclitaxel in platinum-sensitive ovarian cancer patients: results from a 
subset analysis of the CALYPSO phase 3 trial. Ann Oncol. 2012;23(5):1185-1189. 
GLOBOCAN 2012: Europe, Northern America (2012) Estimated Cancer Incidence and 
Mortality, All Ages: Female [database online]. Lyon, France: International Agency for Research 
on Cancer. http://gco.iarc.fr/today/fact-sheets-cancers. Accessed 02 August 2018.  
Grant DJ, Moorman PG, Akushevich L, Palmieri RT, Bentley RC, Schildkraut JM. Primary 
peritoneal and ovarian cancers: an epidemiological comparative analysis. Cancer Causes 
Control. 2010;21(7):991-998. 
Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Ann Rev Immunol. 
2005;23:515-548. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
127 
Griggs J, Mangu P, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients 
with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 
2012;30(13):1553-1561. 
Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. FIGO 26th Annual Report 
on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95(1 
suppl):S161-S192. 
Hoskins P, Eisenhauer E, Beare S, et al. Randomized phase II study of two schedules of 
topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of 
Canada Clinical Trials Group study. J Clin Oncol. 1998;16(6):2233-2237. 
Hoskins PJ, Swenerton KD, Pike JA, et al. Paclitaxel and carboplatin, alone or with irradiation, 
in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol. 2001;19(20):4048-
4053. 
Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ. Coordinately up-regulated genes 
in ovarian cancer. Cancer Res. 2001;61(10):3869-3876. 
Hunder NN, Wallen H, Cao J, et al. Treatment of metastatic melanoma with autologous CD4+ T 
cells against NY-ESO-1. N Engl J Med. 2008;358(25):2698-2703. 
Kalli KR, Oberg AL, Keeney GL, et al. Folate receptor alpha as a tumor target in epithelial 
ovarian cancer. Gynecol Oncol. 2008;108(3):619-629. 
Kelemen LE. The role of folate receptor α in cancer development, progression and treatment: 
cause, consequence or innocent bystander? Int J Cancer. 2006;119(2):243-250. 
Markman M, Kennedy A, Webster K, Peterson G, Kulp B, Belinson J. Phase 2 trial of liposomal 
doxorubicin (40 mg/m2) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and 
primary carcinoma of the peritoneum. Gynecol Oncol. 2000;78(3 pt 1):369-372. 
Mantovani LT, Miotti S, Menard S, et al. Folate binding protein distribution in normal tissues 
and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies 
MOv18 and MOv19. Int J Cancer. 1994;30A(3):363-369. 
Miotti S, Canevari S, Menard S, et al. Characterization of human ovarian carcinoma-associated 
antigens defined by novel monoclonal antibodies with tumor-restricted specificity. Int J Cancer. 
1987;39(3):297-303. 
Muggia FM, Hainsworth JD, Jeffers S, et al. Phase II study of liposomal doxorubicin in 
refractory ovarian cancer: antitumor activity and toxicity modification by liposomal 
encapsulation. J Clin Oncol. 1997;15(3): 987-993. 
Muller P, Kreuzaler M, Khan T, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast 
cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med. 2015;7(315):315ra188. 
Naumann WR, Coleman RL. Management strategies for recurrent platinum-resistant ovarian 
cancer. Drugs. 2011;71(11):1397-1412.  
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
128 
Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T. PD-1 immunoreceptor inhibits B cell 
receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine 
phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci U S A. 2001;98(24):13866-13871. 
O’Malley DM, Moore KN, Vergote I, et al. Safety findings from FORWARD II: A Phase 1b 
study evaluating the folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) 
mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, 
pegylated liposomal doxorubicin (PLD), or pembrolizumab in patients (pts) with ovarian cancer. 
J Clin Oncol. 2017;35(15 suppl):5553. 
O’Malley DM, Martin LP, Gilbert L, et al. Mirvetuximab soravtansine, a folate receptor alpha 
(FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients 
(pts) with platinum-resistant ovarian cancer: Maturing safety and activity profile from the 
FORWARD II phase 1b study. J Clin Oncol. 2018;36(15 suppl):5549. 
O’Shannessy DJ, Jackson SM, Twine NC, et al. Gene expression analyses support fallopian tube 
epithelium as the cell of origin of epithelial ovarian cancer. Int J Mol Sci. 2013;14(7):13687-
13703. 
Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell 
activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543-9553. 
Perren T, Swart A, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J 
Med. 2012;365(26): 2484-2496. 
Pisano C, Cecere SC, Di Napoli M, et al. Clinical trials with pegylated liposomal doxorubicin in 
the treatment of ovarian cancer. J Drug Deliv. 2013;2013:898146. 
Prat J, FIGO Committee on Gynecologic Oncology. FIGO’s staging classification for cancer of 
the ovary, fallopian tube, and peritoneum: abridged republication. J Gynecol Oncol. 
2015;26(2):87-89. 
Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for 
platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III 
trial. J Clin Oncol. 2014;32(13):1302-1308. 
Raja FA, Chopra N, Ledermann JA. Optimal first-line treatment in ovarian cancer. Ann Oncol. 
2012;23(10 suppl):x118-x127. 
Riley JL. PD-1 signaling in primary T cells. Immunol Rev. 2009;229(1):114-125. 
Risch HA, McLaughlin JR, Cole DE, et al. Prevalence and penetrance of germline BRCA1 and 
BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 
2001;68(3):700-710. 
Rosen DG, Yang, G, Liu Guangzhi L, et al. Ovarian cancer: pathology, biology, and disease 
models. Front Biosci (Landmark Ed). 2009;14:2089-2102. 
Rustin GJS, Quinn M, Thigpen T, et al. Re: New guidelines to evaluate the Response to 
Treatment in Solid Tumors (Ovarian Cancer). J Natl Cancer Inst. 2004;96(6):487-488. 
Sheppard KA, Fitz LJ, Lee JM, et al. PD-1 inhibits T-cell receptor induced phosphorylation of 
the ZAP70/CD3 signalosome and downstream signaling to PKC. FEBS Lett. 2004;574(1-3):37-
41. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
129 
ten Bokkel Huinink W, Gore M, Carmichael J, et al. Topotecan versus paclitaxel for the 
treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997;15(6):2183-2193.  
Timmermans M, Sonke GS, Van de Vijver KK, van der Aa MA, Kruitwagen RFPM. No 
improvement in long-term survival for epithelial ovarian cancer patients: A population-based 
study between 1989 and 2014 in the Netherlands. Eur J Cancer. 2018;88:31-37.  
van Dam GM, Themelis G, Crane LM, et al. Intraoperative tumor-specific fluorescence imaging 
in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med. 
2011;17(10):1315-1319. 
Varga A, Piha-Paul SA, Ott PA, et al. Antitumor activity and safety of pembrolizumab in 
patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib 
study. J Clin Oncol. 2015;33(15 suppl):5510. 
Vorobiof DA, Rapoport BL, Slabber CF, et al. Phase 2 study of combination therapy with 
liposomal doxorubicin and carboplatin in patients with relapsed, platinum sensitive ovarian 
cancer. J Clin Oncol. 2004;22(14 suppl):5091. 
Wadler S, Benson A, Engelking C, et al. Recommended guidelines for the treatment of 
chemotherapy-induced diarrhea. J Clin Oncol. 1998;16(9):3169-3178. 
Weitman SD, Lark RH, Coney LR et al. Distribution of the folate receptor GP38 in normal and 
malignant cell lines and tissues. Cancer Res. 1992;52(12):3396-3401. 
Younes A, Kim S, Romaguera J, et al. Phase I multidose-escalation study of the anti-CD19 
maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks 
to patients with relapsed/refractory B-cell lymphoma. J Clin Oncol. 2012;30(22):2776-2782. 
Zhang X, Schwartz JC, Guo X, et al. Structural and functional analysis of the costimulatory 
receptor programmed death-1. Immunity. 2004;20(3):337-347. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
130 
APPENDIX A. 
SCHEDULE OF CLINICAL ASSESSMENTS – REGIMENS A, B, AND E  
Activity 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycle 3 
Cycles 
≥ 4 
End of 
Treatment 
30-Day 
Follow-up 
(+ 14 
Days) 
Day 
1 
Day 
2 
Day
s 8 
& 15 
Day 
1 
Days 
8 & 
15 
Days 15-
21 
Day 
1 
Day 
2 
Days 
8 & 15 
Day 1 
Informed consent 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm disease diagnosis/ 
current stage and prognostic 
index evaluation 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Record baseline signs and 
symptoms 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
Review and document 
IC/EC 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm patient continues to 
satisfy IC/EC 
 
● 
 
 
 
 
 
 
 
 
 
 
 
Confirm patient meets 
re-treatment criteria 
 
 
 
 
● 
 
 
● 
 
 
● 
 
 
Height 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationb 
●c 
● 
 
● 
● 
● 
 
● 
 
 
● 
● 
● 
Weight 
●c 
● 
 
 
● 
 
 
● 
 
 
● 
● 
● 
Vital signsd 
●c 
● 
● 
 
● 
 
 
● 
● 
 
● 
● 
● 
Pulmonary function testse 
●c 
 
 
 
 
 
 
 
 
 
 
 
 
Pulse oximetry 
● 
●r 
● 
● 
●r 
● 
 
●r 
● 
● 
●r 
● 
● 
ECOG PS 
●  
●o 
 
 
● 
 
 
● 
 
 
● 
● 
● 
Hematology and chemistry f 
●c 
● 
 
● 
● 
● 
 
● 
 
● 
● 
● 
● 
Coagulation (PT/INR/aPTT)f  
●c 
● 
 
 
● 
 
 
● 
 
 
● 
 
● 
Urinalysisg, f  
●c 
● 
 
 
● 
 
 
● 
 
 
● 
 
● 
Pregnancy test (urine or 
serum)h 
● 
● 
 
 
● 
 
 
● 
 
 
● 
 
● 
Ophthalmic examinationsi 
●c 
Every other cycle (from point at which toxicity first reported) 
● 
● 
Schirmer testi 
● 
For patients who experience treatment-emergent eye disorders, the Schirmer test will 
be repeated at the first on-study ophthalmic examination and subsequently if clinically 
indicated. 
 
 
Ocular symptom 
assessmenti 
● 
● 
 
 
● 
 
 
● 
 
 
● 
● 
● 
Radiologic tumor 
assessments 
●a 
Every 6 weeks ± 1 week)j 
●k 
●k 
CA125  
●c 
Every 3 weeks (± 1 week)j 
●k 
●k 
12-Lead ECGl 
●c 
● 
● 
 
 
 
 
● 
● 
 
 
● 
●m 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
131 
Activity 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycle 3 
Cycles 
≥ 4 
End of 
Treatment 
30-Day 
Follow-up 
(+ 14 
Days) 
Day 
1 
Day 
2 
Day
s 8 
& 15 
Day 
1 
Days 
8 & 
15 
Days 15-
21 
Day 
1 
Day 
2 
Days 
8 & 15 
Day 1 
Mirvetuximab soravtansine 
administration  
 
● 
 
 
● 
 
 
● 
 
 
● 
 
 
Bevacizumab or carboplatin 
or bevacizumab and 
carboplatin administration   
 
● 
 
 
● 
 
 
● 
 
 
● 
 
 
AE and SAE assessments 
●n 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record concomitant 
medications 
●a 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Lubricating artificial tears 
administrationp 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
Corticosteroid eye drop 
administrationq 
 
● 
● 
● 
● 
● 
 
● 
● 
● 
● 
 
 
a Within 28 days before the start of Cycle 1 Day 1. 
b Directed physical examination is acceptable while on study treatment. A complete physical examination, including assessment of general appearance, skin, 
head (eyes, ears, nose, and throat), neck, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological system, will be completed at screening and 
end of treatment. 
c Screening labs (hematology, clinical chemistry, and urinalysis) and ECG may be performed within 14 days before the first dose before the start of Cycle 1 Day 1. 
Repeat testing on Cycle 1 Day 1 is not required if tests were obtained up to 4 days before dosing and are within acceptable ranges. 
d Vital signs (blood pressure, pulse, respiration rate, and temperature) will be measured as outlined in the full protocol (Section 8.6). 
e Pulmonary function tests should include spirometry, diffusion capacity, and lung volumes. Pulmonary function tests will be performed at screening and in the 
event of pulmonary symptoms as clinically indicated. 
f Day 1 laboratory assessments may be performed up to 4 days before study agent administration. Laboratory results must be reviewed before each scheduled 
administration of mirvetuximab soravtansine and/or bevacizumab or carboplatin. In the event of severe toxicity, laboratory tests must be repeated as necessary 
until the toxicity resolves or stabilizes.  
g For patients receiving bevacizumab, results from urinalysis should be available before dosing because of the increased risk of proteinuria. The test can be 
performed up to 48 hours before dosing. If the test result is +2, bevacizumab should be held until a 24-hour urine test is performed.  
h For WCBP, a urine or serum pregnancy test will be performed at screening, before dosing on Day 1 of every cycle (it can be performed up to 3 days before Day 
1), and at the 30-day follow-up visit. Additional testing may be performed in accordance with institutional requirements or local regulation. 
i Baseline ophthalmic exams will be performed by a board-certified ophthalmologist and will include the following: visual acuity, indirect fundoscopy, slit lamp 
examination under dilatation, intraocular pressure measurement, and corneal photography (when feasible to document corneal abnormalities). A Schirmer test 
will be performed at baseline for all patients, and for patients who experience ocular symptoms, it will be repeated at the first on-study ophthalmic examination 
and subsequently if clinically indicated. Ophthalmic exam may be performed within 14 days before Cycle 1 Day 1. Ocular symptom assessment will be 
performed before the start of each cycle by the treating physician or other qualified individual. If the subject reports ocular symptoms, mirvetuximab soravtansine 
will be stopped, and the subject will be referred to an ophthalmologist for a complete examination (detailed in full protocol). Patients who experience ocular 
toxicity will have a complete ophthalmologic exam performed every other cycle, including patients with blurred vision but normal eye exams. All patients will have 
a complete ophthalmologic exam performed at the end of treatment visit or 30-day follow-up visit. 
j Radiologic tumor assessment by CT scan or MRI is to be performed every 6 weeks (± 1 week) through Week 24 and then every 3 months (± 1 month) for up to 
1 year after randomization, and then either every 6 months (± 1 month) or per standard of care based on symptoms, until the 30-day follow-up visit for Regimens 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
132 
A, B, and E. CA125 will be measured every 3 weeks and at approximately the same time as the radiologic assessment. Patients experiencing CA125 response 
must have a confirmatory test performed at least 28 days after initial response is documented. 
k If a patient discontinues before documentation of PD, a tumor assessment is to be performed at the end of treatment visit or 30-day follow-up visit, if not 
performed within the previous 6 weeks. Tumor assessments will be performed every 12 weeks until progression is documented or the patient begins a new 
treatment regimen. Patients who have discontinued study treatment for reasons other than PD will be followed per RECIST Version 1.1 every 12 weeks 
(± 3 weeks) until documentation of PD, start of subsequent anti-cancer therapy, or for up to 1 year after Cycle 1 Day 1, whichever comes first. 
l Single ECG will be performed at screening, end of treatment, and as clinically indicated. On-study ECGs will be performed in triplicate at each of the following 4 
time points in Cycles 1 and 3: pre-dose (baseline), within 1 hour before first dose of mirvetuximab soravtansine; post-dose, end of mirvetuximab soravtansine 
infusion to coincide with Cmax and PK blood draw (within 1 hour after this blood draw); post-dose, immediately after the end of infusion of the last drug in the 
Regimen to coincide with Cmax and PK blood draw (within 1 hour after this blood draw); 24 ± 2 hours after infusion of mirvetuximab soravtansine to coincide with 
PK blood draw (Section 8.7). 
m As clinically indicated. 
n All AEs and SAEs from the time of informed consent are recorded. 
o ECOG assessment is not necessary on Cycle 1 Day 1 if screening assessment was performed within 3 days before Day 1. 
p Lubricating eye drops are administered every day of the cycle. Patients should be advised to wait at least 15 minutes after corticosteroid eye drop administration 
before instilling lubricating eye drops (Section 5.8.3). 
q Corticosteroid eye drops will be administered on Days 1 through 8 of each cycle (Section 5.8.2). 
r Performed before dosing. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
133 
APPENDIX B. 
SCHEDULE OF CLINICAL ASSESSMENTS – REGIMEN C  
Activity 
Screenin
g 
Cycle 1 
Cycle 2 
Cycle 3 
Cycles 
≥ 4 
End of 
Treat-
ment 
30-Day 
Follow-
up 
(+ 14 
Days) 
Day 
1 
Da
y 2 
Day
s 8 
& 15 
Day 
22 
Day 
1 
Day
s 8 
& 15 
Day 22 
Day 
1 
Da
y 2 
Days 
8 & 
15 
Day 
22 
Day 1 
Informed consent 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm disease 
diagnosis/current stage 
and prognostic index 
evaluation 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record baseline signs 
and symptoms 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review and document 
IC/EC 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm patient 
continues to satisfy 
IC/EC 
 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm patient meets 
re-treatment criteria 
 
 
 
 
 
● 
 
 
● 
 
 
 
● 
 
 
Height 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationb 
●c 
● 
 
● 
 
● 
● 
 
● 
 
 
 
● 
● 
● 
Weight 
●c 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
● 
● 
Vital signsd 
●c 
● 
● 
 
 
● 
 
 
● 
● 
 
 
● 
● 
● 
Pulmonary function 
testse 
●c 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulse oximetry 
● 
●p 
● 
● 
 
●p 
● 
 
●p 
● 
● 
 
●p 
● 
● 
ECOG PS 
●c 
●o 
 
 
 
● 
 
 
● 
 
 
 
● 
● 
● 
Hematology and 
chemistryf  
●c 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Coagulation (PT/INR/ 
aPTT)f  
●c 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
 
● 
Urinalysis f 
●c 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
 
● 
Pregnancy test (urine or 
serum)g 
● 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
 
● 
ECHO/MUGAh 
● 
 
 
 
 
 
 
 
 
 
 
 
Every four 
cycles or 
as 
● 
 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
134 
Activity 
Screenin
g 
Cycle 1 
Cycle 2 
Cycle 3 
Cycles 
≥ 4 
End of 
Treat-
ment 
30-Day 
Follow-
up 
(+ 14 
Days) 
Day 
1 
Da
y 2 
Day
s 8 
& 15 
Day 
22 
Day 
1 
Day
s 8 
& 15 
Day 22 
Day 
1 
Da
y 2 
Days 
8 & 
15 
Day 
22 
Day 1 
clinically 
indicated 
Ophthalmic 
examinationsi 
● 
Every other cycle (from point at which toxicity first reported)i 
● 
● 
Schirmer testi 
● 
For patients who experience treatment-emergent eye disorders, the Schirmer test will be 
repeated at the first on-study ophthalmic examination and subsequently if clinically indicated. 
 
 
Ocular symptom 
assessmenti 
● 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
● 
● 
Radiologic tumor 
assessments 
●a 
Every 8 weeks (± 1 week)j 
●k 
●k 
CA125  
●c 
Every 4 weeks (± 1 week)j 
●k 
●k 
12-Lead ECGl 
●c 
● 
● 
 
 
 
 
 
● 
● 
 
 
 
● 
●m 
Mirvetuximab 
soravtansine 
administration   
 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
 
 
Pegylated liposomal 
doxorubicin 
administration  
 
● 
 
 
 
● 
 
 
● 
 
 
 
● 
 
 
AE and SAE 
assessments 
●n 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record concomitant 
medications 
●a 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Lubricating artificial 
tears administrationq 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
Corticosteroid eye drop 
administrationr 
 
● 
● 
● 
 
● 
● 
 
● 
● 
● 
 
● 
 
 
a Within 28 days before the start of Cycle 1 Day 1. 
b Directed physical examination is acceptable while on study treatment. A complete physical examination, including assessment of general appearance, skin, 
head (eyes, ears, nose, and throat), neck, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological system, will be completed at screening and 
end of treatment. 
c Screening labs (hematology, clinical chemistry, and urinalysis), CA125, and ECG may be performed within 14 days before the first dose before the start of Cycle 
1 Day 1. Repeat testing on Cycle 1 Day 1 is not required if tests were obtained up to 4 days before dosing and are within acceptable ranges. 
d Vital signs (blood pressure, pulse, respiration rate, and temperature) will be measured as outlined in the full protocol Section 8.6. 
e Pulmonary function tests should include spirometry, diffusion capacity, and lung volumes. Pulmonary function tests will be performed at screening and in the 
event of pulmonary symptoms as clinically indicated. 
f Day 1 laboratory assessments may be performed up to 4 days before study agent administration. Laboratory results must be reviewed before each scheduled 
administration of mirvetuximab soravtansine and/or pegylated liposomal doxorubicin. In the event of severe toxicity, laboratory tests must be repeated as 
necessary until the toxicity resolves or stabilizes.  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
135 
g For WCBP, a urine or serum pregnancy test will be performed at screening, before dosing on Day 1 of every cycle (it can be performed up to 3 days before Day 
1), and at the 30-day follow-up visit. Additional testing may be performed in accordance with institutional requirements or local regulation. 
h The same assessment technique should be used throughout the study. If the patient’s left ventricular ejection fraction drops below normal or by at least 15% 
from the baseline value, pegylated liposomal doxorubicin should be stopped. To be performed at screening, every four cycles or as clinically indicated, and at 
the end of treatment visit. 
i Baseline ophthalmic exams will be performed by a board-certified ophthalmologist and will include the following: visual acuity, indirect fundoscopy, slit lamp 
examination under dilatation, intraocular pressure measurement, and corneal photography (when feasible to document corneal abnormalities). A Schirmer test 
will be performed at baseline for all patients, and for patients who experience ocular symptoms, it will be repeated at the first on-study ophthalmic examination 
and subsequently if clinically indicated. Ophthalmic exam may be performed within 14 days before Cycle 1 Day 1. Ocular symptom assessment will be 
performed before the start of each cycle by the treating physician or other qualified individual. If the subject reports ocular symptoms, mirvetuximab soravtansine 
will be stopped, and the subject will be referred to an ophthalmologist for a complete examination (detailed in full protocol). Patients who experience ocular 
toxicity will have a complete ophthalmologic exam performed every other cycle, including patients with blurred vision but normal eye exams. All patients will have 
a complete ophthalmologic exam performed at the end of treatment visit or 30-day follow-up visit. 
j Radiologic tumor assessment by CT scan or MRI is to be performed every 8 weeks (± 1 week) for Regimen C up until 1 year after randomization, and thereafter 
every 16 weeks (± 4 weeks) or as clinically indicated. CA125 will be measured every 4 weeks and at approximately the same time as radiologic assessment. 
Patients experiencing CA125 response must have a confirmatory test performed at least 28 days after initial response is documented. 
k If a patient discontinues before documentation of PD, a tumor assessment is to be performed at the end of treatment visit or 30-day follow-up visit, if not 
performed within the previous 6 weeks. Tumor assessments will be performed every 12 weeks until progression is documented or the patient begins a new 
treatment regimen. Patients who have discontinued study treatment for reasons other than PD will be followed per RECIST Version 1.1 every 12 weeks 
(± 3 weeks) until documentation of PD, start of subsequent anti-cancer therapy, or for up to 1 year after Cycle 1 Day 1, whichever comes first. 
l Single ECG will be performed at screening, end of treatment, and as clinically indicated. On-study ECGs will be performed in triplicate at each of the following 4 
time points in Cycles 1 and 3: pre-dose (baseline), within 1 hour before first dose of mirvetuximab soravtansine; post-dose, end of mirvetuximab soravtansine 
infusion to coincide with Cmax and PK blood draw (within 1 hour after this blood draw); post-dose, immediately after the end of infusion of the last drug in the 
Regimen to coincide with Cmax and PK blood draw (within 1 hour after this blood draw); 24 ± 2 hours after infusion of mirvetuximab soravtansine to coincide with 
PK blood draw (Section 8.7). 
m As clinically indicated. 
n All AEs and SAEs from the time of informed consent are recorded. 
o ECOG assessment is not necessary on Cycle 1 Day 1 if screening assessment was performed within 3 days before Day 1. 
p Performed before dosing. 
q Lubricating eye drops are administered every day of the cycle. Patients should be advised to wait at least 15 minutes after corticosteroid eye drop administration 
before instilling lubricating eye drops (Section 5.8.3). 
r Corticosteroid eye drops will be administered on Days 1 through 8 of each cycle (Section 5.8.2). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
136 
APPENDIX C. 
SCHEDULE OF CLINICAL ASSESSMENTS – REGIMEN D  
Activity 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycle 3 
Cycles 
≥ 4 
End of 
Treatment 
30-Day 
Follow-up 
(+ 14 
Days) 
Day 
1 
Day 
2 
Day
s 8 
& 15 
Day 
1 
Days 
8 & 
15 
Days 15-
21 
Day 
1 
Day 
2 
Days 
8 & 15 
Day 1 
Informed consent 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm disease 
diagnosis/current stage and 
prognostic index evaluation 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Record baseline signs and 
symptoms 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
Review and document 
IC/EC 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm patient continues to 
satisfy IC/EC 
 
● 
 
 
 
 
 
 
 
 
 
 
 
Confirm patient meets 
re-treatment criteria 
 
 
 
 
● 
 
 
● 
 
 
● 
 
 
Biopsy of tumor 
 
●b 
 
 
 
●b 
 
 
 
 
 
 
 
Height 
●a 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationc 
●d 
● 
 
● 
● 
● 
 
● 
 
 
● 
● 
● 
Weight 
●d 
● 
 
 
● 
 
 
● 
 
 
● 
● 
● 
Vital signse 
●d 
● 
● 
 
● 
 
 
● 
● 
 
● 
● 
● 
Pulmonary function testsf 
●d 
 
 
 
 
 
 
 
 
 
 
 
 
Pulse oximetry 
● 
●s 
● 
● 
●s 
● 
 
●s 
● 
● 
●s 
● 
● 
ECOG PS 
●d 
●g 
 
 
● 
 
 
● 
 
 
● 
● 
● 
Hematology and chemistry h 
●d 
● 
 
● 
● 
● 
 
● 
 
● 
● 
● 
● 
Thyroid paneli 
●d 
● 
 
 
 
 
 
● 
 
 
● 
● 
● 
Coagulation (PT/INR/aPTT)h  
●d 
● 
 
 
● 
 
 
● 
 
 
● 
 
● 
Urinalysish 
●d 
● 
 
 
● 
 
 
● 
 
 
● 
 
● 
Pregnancy test (urine or 
serum)j 
● 
● 
 
 
● 
 
 
● 
 
 
● 
 
● 
Ophthalmic examinationsk 
●d 
Every other cycle (from point at which toxicity first reported)k 
● 
● 
Schirmer testk 
● 
For patients who experience treatment-emergent eye disorders, the Schirmer test will 
be repeated at the first on-study ophthalmic examination and subsequently if clinically 
indicated. 
 
 
Ocular symptom 
assessmentk 
● 
● 
 
 
● 
 
 
● 
 
 
● 
● 
● 
Radiologic tumor 
assessments 
●a 
Every 6 weeks (± 1 week)l 
●m 
●m 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
137 
Activity 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycle 3 
Cycles 
≥ 4 
End of 
Treatment 
30-Day 
Follow-up 
(+ 14 
Days) 
Day 
1 
Day 
2 
Day
s 8 
& 15 
Day 
1 
Days 
8 & 
15 
Days 15-
21 
Day 
1 
Day 
2 
Days 
8 & 15 
Day 1 
CA125  
●d 
Every 3 weeks (± 1 week)l 
●m 
●m 
12-Lead ECGn 
●d 
● 
● 
 
 
 
 
● 
● 
 
 
● 
●o 
Mirvetuximab soravtansine 
administration  
 
● 
 
 
● 
 
 
● 
 
 
● 
 
 
Pembrolizumab 
administration   
 
● 
 
 
● 
 
 
● 
 
 
● 
 
 
AE and SAE assessments 
●p 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record concomitant 
medications 
●a 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Lubricating artificial tears 
administrationq 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
Corticosteroid eye drop 
administrationr 
 
● 
● 
● 
● 
● 
 
● 
● 
● 
● 
 
 
a Within 28 days before the start of Cycle 1 Day 1. 
b A minimum of two new tumor tissue samples is required during this study (a baseline sample and Cycle 2 Day 8 sample). Before screening, all patients must 
submit a tumor tissue sample (pre-screening sample) for analysis of FRα. The prescreening sample may either be archived tumor tissue samples (formalin-
fixed, paraffin embedded blocks, or slides sectioned from such blocks), or if archival samples are not available, new biopsy samples must be provided. If a new 
biopsy sample is required for a baseline sample, it will be taken before the first dose of study drug; if a new biopsy sample was provided for FRα pre-screening, 
it can be used as the baseline sample. A second tumor tissue sample will be taken on Cycle 2 Day 8 (± 3 days). Once the FRα status of a patient has been 
established, new biopsies should be taken only if, in the opinion of the Investigator, there is no concern of significant risk to the patient (Section 7.1.1). 
c Directed physical examination is acceptable while on study treatment. A complete physical examination, including assessment of general appearance, skin, 
head (eyes, ears, nose, and throat), neck, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological system, will be completed at screening and 
end of treatment. 
d Screening labs (hematology, clinical chemistry, and urinalysis), CA125, and ECG may be performed within 14 days before the first dose before the start of Cycle 
1 Day 1. Repeat testing on Cycle 1 Day 1 is not required if tests were obtained up to 4 days before dosing and are within acceptable ranges. 
e Vital signs (blood pressure, pulse, respiration rate, and temperature) will be measured as outlined in the full protocol (Section 8.6). 
f Pulmonary function tests should include spirometry, diffusion capacity, and lung volumes. Pulmonary function tests will be performed at screening and in the 
event of pulmonary symptoms as clinically indicated. 
g ECOG assessment is not necessary on Cycle 1 Day 1 if screening assessment was performed within 3 days before Day 1. 
h Day 1 laboratory assessments may be performed up to 4 days before study agent administration. Laboratory results must be reviewed before each scheduled 
administration of mirvetuximab soravtansine and pembrolizumab. In the event of severe toxicity, laboratory tests must be repeated as necessary until the toxicity 
resolves or stabilizes.  
i The thyroid panel includes T3 or free T3, free T4, and TSH. Testing will be performed every 6 weeks during the study. 
j For WCBP, a urine or serum pregnancy test will be performed at screening, before dosing on Day 1 of every cycle (it can be performed up to 3 days before Day 
1), and at the 30-day follow-up visit. Additional testing may be performed in accordance with institutional requirements or local regulation. 
k Baseline ophthalmic exams will be performed by a board-certified ophthalmologist and will include the following: visual acuity, indirect fundoscopy, slit lamp 
examination under dilatation, intraocular pressure measurement, and corneal photography (when feasible to document corneal abnormalities). A Schirmer test 
will be performed at baseline for all patients, and for patients who experience ocular symptoms, it will be repeated at the first on-study ophthalmic examination 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
138 
and subsequently if clinically indicated. Ophthalmic exam may be performed within 14 days before Cycle 1 Day 1. Ocular symptom assessment will be 
performed before the start of each cycle by the treating physician or other qualified individual. If the subject reports ocular symptoms, mirvetuximab soravtansine 
will be stopped, and the subject will be referred to an ophthalmologist for a complete examination (detailed in full protocol). Patients who experience ocular 
toxicity will have a complete ophthalmologic exam performed every other cycle, including patients with blurred vision but normal eye exams. All patients will have 
a complete ophthalmologic exam performed at the end of treatment visit or 30-day follow-up visit. 
l Radiologic tumor assessment by CT scan or MRI is to be performed every 6 weeks (± 1 week) through Week 24 and then every 3 months (± 1 month) for up to 
1 year after randomization, and then either every 6 months ((± 1 month) or per standard of care based upon symptoms, until the 30-day follow-up visit. CA125 
will be measured every 3 weeks and at approximately the same time as radiologic assessment. Patients experiencing CA125 response must have a 
confirmatory test performed at least 28 days after initial response is documented. 
m If a patient discontinues before documentation of PD, a tumor assessment is to be performed at the end of treatment visit or 30-day follow-up visit, if not 
performed within the previous 6 weeks. Tumor assessments will be performed every 12 weeks until progression is documented or the patient begins a new 
treatment regimen. Patients who have discontinued study treatment for reasons other than PD will be followed per RECIST Version 1.1 every 12 weeks 
(± 3 weeks) until documentation of PD, start of subsequent anti-cancer therapy, or for up to 1 year after Cycle 1 Day 1, whichever comes first. 
n Single ECG will be performed at screening, end of treatment, and as clinically indicated. On-study ECGs will be performed in triplicate at each of the following 4 
time points in Cycles 1 and 3: pre-dose (baseline), within 1 hour before first dose of mirvetuximab soravtansine; post-dose, end of mirvetuximab soravtansine 
infusion to coincide with Cmax and PK blood draw (within 1 hour after this blood draw); post-dose, immediately after the end of infusion of the last drug in the 
Regimen to coincide with Cmax and PK blood draw (within 1 hour after this blood draw); 24 ± 2 hours after infusion of mirvetuximab soravtansine to coincide with 
PK blood draw (Section 8.7). 
o As clinically indicated. 
p All AEs and SAEs from the time of informed consent are recorded. 
q Lubricating eye drops are administered every day of the cycle. Patients should be advised to wait at least 15 minutes after corticosteroid eye drop administration 
before instilling lubricating eye drops (Section 5.8.3). 
r Corticosteroid eye drops will be administered on Days 1 through 8 of each cycle (Section 5.8.2). 
s Performed before dosing. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
139 
APPENDIX D. 
BLOOD SAMPLE COLLECTION FOR PHARMACOKINETICS, IMMUNOGENICITY, AND 
BIOMARKER ASSESSMENTS – REGIMENS A, B, C, D, AND E 
Regimen 
Cycles 1 and 3 
Cycles 2, 4, 5, and 6 
End of Treatment and  
30-Day Follow-up 
A 
B 
C 
D 
E 
A 
B 
C 
D 
E 
A 
B 
C 
D 
E 
Day 1, pre-dosea 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
 
 
Day 1, end of mirvetuximab soravtansine 
infusionb 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
 
 
Day 1, after combination infusionc 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
 
 
Day 1, 6 hoursd 
● 
● 
● 
● 
● 
 
 
 
 
 
 
 
 
 
 
Day 2, 24 hourse 
● 
● 
● 
● 
● 
 
 
 
 
 
 
 
 
 
 
Day 3, 48 hoursf 
● 
● 
● 
● 
● 
 
 
 
 
 
 
 
 
 
 
Day 8g 
● 
● 
● 
● 
● 
 
 
 
 
 
 
 
 
 
 
Day 15g 
● 
● 
● 
● 
● 
 
 
 
 
 
 
 
 
 
 
Day 22g 
 
 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Study visitg 
 
 
 
 
 
 
 
 
 
 
● 
● 
● 
● 
● 
a Predose samples to be collected before the start of the first infusion, and to also include a sample for the FcγR biomarker assessment. All patients will be 
genotyped for FcγR alleles via peripheral blood mononuclear cell analysis at Cycle 1 Day 1.  
b Immediately after completion of mirvetuximab soravtansine infusion (+ 10 minutes). 
c Cohorts A, B, C, and D: sample collected immediately after completion of bevacizumab/carboplatin/pegylated liposomal doxorubicin/pembrolizumab infusion (+ 
10 minutes). Cohort E: samples to be collected immediately after completion of bevacizumab infusion (+ 10 minutes) and immediately after completion of 
carboplatin infusion (+ 10 minutes). 
d 6 hours after completion of mirvetuximab soravtansine infusion (+ 20 minutes). 
e 24 hours after completion of mirvetuximab soravtansine infusion (± 2 hours). 
f 48 hours after completion of mirvetuximab soravtansine infusion (± 2 hours). 
g A single sample collected when safety assessments are performed. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
140 
APPENDIX E. 
PEMBROLIZUMAB BACKGROUND 
Pharmaceutical and Therapeutic Background 
The importance of intact immune surveillance function in controlling outgrowth of neoplastic 
transformations has been known for decades (Disis 2010). Accumulating evidence shows a 
correlation between tumor-infiltrating lymphocytes in cancer tissue and favorable prognosis in 
various malignancies. In particular, the presence of CD8+ T cells and the ratio of CD8+ effector 
T cells/FoxP3+ regulatory T cells correlates with improved prognosis and long-term survival in 
solid malignancies, such as ovarian, colorectal, and pancreatic cancer; hepatocellular carcinoma; 
malignant melanoma; and renal cell carcinoma. Tumor-infiltrating lymphocytes can be expanded 
ex vivo and reinfused, inducing durable objective tumor responses in cancers such as melanoma 
(Dudley 2005, Hunder 2008). 
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune 
control. The normal function of PD-1, expressed on the cell surface of activated T cells under 
healthy conditions, is to down-modulate unwanted or excessive immune responses, including 
autoimmune reactions. PD-1 (encoded by the gene Pdcd1) is an Ig superfamily member related 
to CD28 (cluster of differentiation 28) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 
4) that has been shown to negatively regulate antigen receptor signaling upon engagement of its 
ligands (PD-L1 and/or PD-L2) (Greenwald 2005, Okazaki 2001). 
The structure of murine PD-1 has been resolved (Zhang 2004). PD-1 and its family members are 
type I transmembrane glycoproteins containing an Ig-variable–type domain responsible for 
ligand binding and a cytoplasmic tail responsible for the binding of signaling molecules. The 
cytoplasmic tail of PD-1 contains 2 tyrosine-based signaling motifs, an immunoreceptor 
tyrosine-based inhibition motif, and an immunoreceptor tyrosine-based switch motif. Following 
T-cell stimulation, PD-1 recruits the tyrosine phosphatases SHP-1 and SHP-2 to the 
immunoreceptor tyrosine-based switch motif within its cytoplasmic tail, leading to the 
dephosphorylation of effector molecules such as CD3 zeta, protein kinase C-theta, and zeta-
chain–associated protein kinase, which are involved in the CD3 T-cell signaling cascade 
(Okazaki 2001, Chemnitz 2004, Sheppard 2004, and Riley 2009). The mechanism by which PD-
1 down-modulates T-cell responses is similar to, but distinct from, that of CTLA-4 because both 
molecules regulate an overlapping set of signaling proteins (Parry 2005, Francisco 2010). As a 
consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic intervention in 
EOC.  
Nonclinical and Clinical Trials 
Therapeutic studies in mouse models have shown that administration of antibodies blocking 
PD-1/PD-L1 interaction enhances infiltration of tumor-specific CD8+ T cells and ultimately 
leads to tumor rejection, either as a monotherapy or in combination with other treatment 
modalities. Anti-mouse PD-1 or anti-mouse PD-L1 antibodies have demonstrated antitumor 
responses in models of squamous cell carcinoma, pancreatic carcinoma, melanoma, acute 
myeloid leukemia, and colorectal carcinoma. In such studies, tumor infiltration by CD8+ T cells 
and increased interferon γ, granzyme B, and perforin expression were observed, indicating that 
the mechanism underlying the anti-tumor activity of PD-1 checkpoint inhibition involved local 
infiltration and activation of effector T-cell function in vivo. Experiments have confirmed the in 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
141 
vivo efficacy of anti-mouse PD-1 antibody as a monotherapy, and in combination with 
chemotherapy, in syngeneic mouse tumor models. 
Justification for Dose  
The planned dose of pembrolizumab for this study is 200 mg Q3W. Based on the totality of data 
generated in the Keytruda development program, 200 mg Q3W is the appropriate dose of 
pembrolizumab for adults across all indications and regardless of tumor type. As outlined below, 
this dose is justified by: 
• Clinical data from 8 randomized studies demonstrating flat dose– and exposure-
efficacy relationships from 2 mg/kg Q3W to 10 mg/kg Q2W 
• Clinical data showing meaningful improvement in benefit-risk, including overall 
survival at 200 mg Q3W across multiple indications 
• Pharmacology data showing full target saturation in both systemic circulation 
(inferred from PK data) and tumor (inferred from physiologically based PK analysis) 
at 200 mg Q3W 
Among the 8 randomized dose-comparison studies, a total of 2,262 participants were enrolled 
with melanoma and NSCLC, covering different disease settings (treatment naïve, previously 
treated, PD-L1 enriched, and all comers) and different treatment settings (monotherapy and in 
combination with chemotherapy). Five studies compared 2 mg/kg Q3W with 10 mg/kg Q2W 
(KN001 Cohort B2, KN001 Cohort D, KN002, KN010, and KN021), and 3 studies compared 
10 mg/kg Q3W with 10 mg/kg Q2W (KN001 Cohort B3, KN001 Cohort F2, and KN006). All of 
these studies demonstrated flat dose– and exposure-response relationships across the doses 
studied, representing an approximate 5- to 7.5-fold difference in exposure. The 2 mg/kg (or 
200 mg fixed dose) Q3W regimen provided similar responses to the highest doses studied. 
Subsequently, flat dose exposure-response relationships were also observed in other tumor types 
including head and neck cancer, bladder cancer, gastric cancer, and classical Hodgkin 
lymphoma, confirming 200 mg Q3W as the appropriate dose, independent of the tumor type. 
These findings are consistent with the mechanism of action of pembrolizumab, which acts by 
interaction with immune cells, and not via direct binding to cancer cells. 
Additionally, pharmacology data clearly show target saturation at 200 mg Q3W. First, PK data in 
KN001 evaluating target-mediated drug disposition conclusively demonstrated saturation of 
PD-1 in systemic circulation at doses much lower than 200 mg Q3W. Second, a physiologically 
based PK analysis was conducted to predict tumor PD-1 saturation over a wide range of tumor 
penetration and PD-1 expression. This evaluation concluded that pembrolizumab at 200 mg 
Q3W achieves full PD-1 saturation in both blood and tumor. 
Finally, population PK analysis of pembrolizumab, which characterized the influence of body 
weight and other participant covariates on exposure, has shown that fixed dosing provides 
similar control of PK variability as weight-based dosing, with considerable overlap in the 
distribution of exposures from the 200 mg Q3W fixed dose and 2 mg/kg Q3W dose. Supported 
by these PK characteristics, and given that fixed dosing has advantages of reduced dosing 
complexity and reduced potential for dosing errors, the 200 mg Q3W fixed dose was selected for 
evaluation across all pembrolizumab protocols. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
142 
APPENDIX F. 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS SCALE 
Sources: Muggia 1997 and Oken 1982. 
Grade 
Scale 
0 
Fully active, able to carry out all pre-disease performance without restriction 
(Karnofsky 90-100) 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, eg, light housework, office work (Karnofsky 70-80) 
2 
Ambulatory and capable of all self-care but unable to carry out work activities; up and 
about more than 50% of waking hours (Karnofsky 50-60) 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours (Karnofsky 30-40) 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair. 
(Karnofsky 10-20) 
APPENDIX G. 
RESPONSE DEFINITION (RECIST VERSION 1.1) 
Source: Eisenhauer 2009. 
DEFINITIONS 
Baseline: Baseline is defined as the most recent assessment performed before the first dose of 
study treatment. Baseline assessments must be performed within the period defined in the 
protocol eligibility criteria. 
Measurable Lesions: Except for lymph nodes (described below), measurable lesions are defined 
as those that can be accurately measured in at least one dimension (longest diameter to be 
recorded) as ≥ 10 mm with CT scan (if CT scans have slice thickness greater than 5 mm, the 
minimum size of a measurable lesion is twice the slice thickness).  
• To be considered pathologically enlarged and measurable, a lymph node must be 
≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the 
short axis will be measured and recorded. 
• Magnetic resonance imaging may be substituted for contrast-enhanced CT for lesions 
at some anatomical sites, but not for lesions in the lungs. The minimum size for 
measurability is the same as for CT scan (10 mm) as long as the scans are performed 
with slice thickness of 5 mm and no gap. If MRI is performed with thicker slices, the 
size of a measurable lesion at baseline should be twice the slice thickness. If there are 
inter-slice gaps, this also needs to be considered in determining the size of measurable 
lesions at baseline. 
Non-measurable Lesions: All other lesions (or sites of disease), including small lesions (longest 
diameter < 10 mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis), are considered 
non-measurable.  
• Lymph nodes that have a short axis < 10 mm are considered non-pathological and are 
not to be recorded or followed.  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
143 
• Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses 
(not followed by CT scan or MRI) are considered non-measurable. 
Target Lesions: All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in 
total, representative of all involved organs, are to be identified as target lesions and measured 
and recorded at baseline.  
• Target lesions are to be selected on the basis of their size (lesions with the longest 
diameter) to represent all involved organs, and to be those that lend themselves to 
reproducible repeated measurements.  
• On occasion, the largest lesion may not lend itself to reproducible measurement; in 
this case, the next-largest lesion that can be measured reproducibly should be 
selected. 
• Target lesions will be measured at each assessment (longest axis for non-nodal 
lesions, shortest axis for measurable malignant nodal lesions). 
Non-target Lesions: All other lesions (or sites of disease) including all non-measurable lesions 
(including pathological lymph nodes with ≥ 10 to < 15 mm short axis) and all measurable lesions 
beyond the 5 target lesions are to be identified as non-target lesions and recorded at baseline.  
• Measurements of these lesions are not required, but the presence, absence, and 
unequivocal progression of each is to be recorded throughout follow-up.  
• Lymph nodes that have a short axis < 10 mm are considered non-pathological and are 
not to be recorded or followed. 
Special Considerations 
Clinical Examination of Lesions: Superficial or visible lesions that cannot be assessed by CT 
scan or MRI will be considered for response assessment only if these lesions are biopsy-proven 
metastatic lesions and ≥ 10 mm in diameter. These lesions will be considered non-measurable, 
and thus non-target, for response assessment. 
Cystic Lesions: Cystic lesions thought to represent cystic metastases can be considered 
measurable lesions if they meet the definition of measurability described above. However, if 
non-cystic lesions are present in the same patient, these are preferred for selection as target 
lesions.  
Bone Lesions: Bone scan, positron emission tomography (PET) scan, and plain films are not 
considered adequate imaging techniques to measure bone lesions. However, these techniques can 
be used to confirm the presence or disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross-sectional imaging techniques such as CT 
scan or MRI be considered measurable lesions if the soft tissue component meets the 
definition of measurability described above. 
• Blastic bone lesions are non-measurable. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
144 
Lesions With Prior Local Treatment: Lesions situated in a previously irradiated area, or in an 
area subjected to other loco-regional therapy, are usually not considered measurable; however, if 
they meet the following criteria, they may be considered for study: 
• There has been prior documented progression in the lesion by at least 2 sequential CT 
scans or MRIs performed after the completion of radiation. 
OR 
• There is histopathological evidence of progression. 
Additionally, if such lesions meet the criteria for measurability, they may be considered target 
lesions. 
Imaging Methods 
The same method of assessment and the same technique used to characterize each identified and 
reported lesion at baseline should be used during each follow-up assessment. Imaging-based 
evaluation is preferred to evaluation by clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessable by clinical exam (referring to biopsy-proven visible 
lesions(s) at the vaginal apex).  
Chest X-ray: Lesions that are identified on chest x-ray must be confirmed and followed by CT 
scan. If there is/are pre-existing chest lesion(s) before the baseline tumor assessment, a chest 
x-ray is not necessary to assess those lesions. The pre-existing chest lesion(s) must be assessed at 
baseline and followed by CT scans. 
Conventional CT Scan or MRI: This guideline has defined measurability of lesions on CT scan 
on the basis of the assumption that CT scan slice thickness is 5 mm or less. If CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion is twice the slice 
thickness. Magnetic resonance imaging is also acceptable in certain situations (eg, for body 
scan), except for lungs.  
CA125: Tumor marker CA125 alone cannot be used to assess response or determine 
progression; however, it will be followed. CA125 measurements should be scheduled to 
approximately coincide with radiologic assessment (every 6 weeks ± 1 week). Patients whose 
CA125 is above the ULN at baseline will need to have their values normalize to ≤ the ULN, in 
addition to complete disappearance of measurable or evaluable disease, to be considered in CR. 
Other methods of assessment (eg, PET-CT, ultrasound, and fluorodeoxyglucose PET) should not 
be used for response assessment in this study. 
Time Point Assessments 
Patients will have tumor measurements performed within 28 days before baseline and every 
6 weeks thereafter (± 1 week). 
At baseline, tumors and lymph nodes are classified and documented as target or non-target per 
the definitions provided above. It is possible to record multiple non-target lesions involving the 
same organ as a single item (eg, multiple liver metastases).  
At all post-baseline evaluations, the baseline classification (target or non-target) is to be 
maintained, and lesions are to be documented and described in a consistent fashion over time 
(eg, recorded in the same order on source documents and CRFs). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
145 
For target lesions, measurements should be taken and recorded in metric notation. All tumor 
measurements must be recorded in millimeters. 
At each assessment, a sum of the diameters (longest for non-nodal lesions, short axis for nodal 
lesions) for all target lesions will be calculated and reported. The baseline sum of the longest 
diameters (SLD) will be used as reference to further characterize any objective tumor regression 
in the measurable dimension of the disease. The lowest SLD (nadir) since, and including, the 
baseline value will be used as reference for evaluating progression. 
After baseline, the actual size of the target lesion should be documented, if possible, even if the 
lesions become very small. If in the opinion of the radiologist, the lesion has likely disappeared, 
0 mm should be recorded. If the lesion is present but too small to measure, an indicator of “too 
small to measure” will be provided on the CRF (a default value of 5 mm will be imputed during 
analysis).  
Non-target lesions are to be assessed qualitatively (present, resolved, or unequivocal 
progression) and new lesions, if any, are to be documented separately. 
At each evaluation, a time point response is to be determined for target lesions, non-target 
lesions, new lesions, and overall. 
Time Point Response Criteria 
Target Lesion Time Point Response (TPR) 
Complete response 
(CR) 
Disappearance of all target lesions. All pathological lymph nodes (whether target 
or non-target) must have reduction in short axis to < 10 mm.  
Partial response 
(PR) 
At least 30% decrease in the SLD of target lesions, taking as reference the 
baseline SLD. 
Progressive 
disease (PD) 
At least a 20% increase in the SLD of target lesions, taking as reference the 
smallest (nadir) SLD since and including baseline. In addition to the relative 
increase of 20%, the SLD must also demonstrate an absolute increase of at 
least 5 mm. 
Stable disease 
(SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for 
PD. 
Not applicable (NA) 
No target lesions identified at baseline. 
Unable to evaluate 
(UE) 
One or more target lesions are not imaged, and the remainder of the SLD 
compared with the nadir SLD does not meet the criteria for PD. 
If the target lesion for a patient meets the criteria for both PR and PD at a given time point, the target 
lesion response is PD. 
If the nadir SLD is 0 (ie, the patient had a prior target lesion CR), the re-appearance of any prior target 
lesions to any degree constitutes PD. 
Non-target Lesion TPR 
Complete response 
(CR) 
Disappearance of all non-target lesions and normalization of tumor marker level 
if tumor marker at baseline is above the ULN. All lymph nodes must be non-
pathological in size (< 10 mm short axis).  
Non-CR/non-PD 
Persistence of one or more non-target lesion(s) and/or maintenance of CA125 
above the normal limits if CA125 at baseline is above the ULN. 
Progressive 
disease (PD) 
Unequivocal progression of non-target lesions. Unequivocal progression should 
not normally trump target lesion status. It must be representative of overall 
disease status change, not a single lesion increase. 
Not applicable (NA) 
No non-target lesions identified at baseline. 
Unable to evaluate 
(UE) 
One or more non-target lesions are not imaged, and the remaining non-target 
lesions do not meet the criteria for PD. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
146 
If the target lesion for a patient meets the criteria for both PR and PD at a given time point, the target 
lesion response is PD. 
If the nadir SLD is 0 (ie, the patient had a prior target lesion CR), the re-appearance of any prior target 
lesions to any degree constitutes PD. 
New Lesion TPR 
Yes 
Lesion present at follow-up visit either for the very first time or re-appearing (ie, 
lesion was present at baseline, disappeared at a follow-up visit, and re-appeared 
later). 
No 
No new lesions present at follow-up. 
Unable to evaluate 
(UE) 
Patient not assessed or incompletely assessed for new lesion. 
Determining Overall Time Point Response 
Target Lesion TPR 
Non-target TPR 
New Lesions TPR 
Overall TPR 
CR 
CR or NA 
No 
CR* 
CR 
Non-CR/non-PD 
No 
PR* 
CR 
UE 
No 
PR* 
PR 
Non-PD or NA or UE 
No 
PR* 
SD 
Non-PD or NA or UE 
No 
SD 
UE 
Non-PD 
No 
UE 
PD 
Any 
No or Yes or UE 
PD 
Any 
PD 
No or Yes or UE 
PD 
Any 
Any 
Yes 
PD 
NA 
CR 
No 
CR* 
NA 
Non-CR/non-PD 
No 
Non-CR/non-PD 
Non-PD 
Non-PD 
UE 
UE 
* Patients with an overall response of CR or PR must have a repeat tumor assessment performed no fewer than 
4 weeks after the criteria for response are first met. 
Any = CR, PR, SD, PD, NA, or UE. 
The overall response at a given time point does not depend on the overall response assigned at any prior time 
point. 
Confirmation: The main goal of confirmation of objective response is to avoid overestimating 
the observed response rate. For patients with an overall response of PR or CR at a given time 
point, changes in tumor measurements must be confirmed by repeat assessments that should be 
performed no fewer than 4 weeks after the criteria for response are first met. However, the 
presence or absence of confirmation is not considered when assigning a time point response. 
Best Overall Response: Best overall response, incorporating confirmation requirements, will be 
derived during statistical analysis from the series of time point responses and need not be 
considered when assigning response at any time point. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
147 
APPENDIX H. 
GYNECOLOGIC CANCER INTERGROUP CRITERIA FOR 
EVALUATION OF CA125 
Source: Rustin 2004. 
On the basis of the available data and extensive discussions among the cooperative groups within 
the GCIG, it is recommended that the following definition of response be used in ovarian cancer 
studies so that response can be measured by either RECIST or CA125 criteria. If the response is 
evaluable by both criteria, then the date of response will be the date of the earlier of the two 
events. 
Definition of Response 
Greater than or equal to 50% reduction in CA125 levels from baseline: 
• The response must be confirmed and maintained for at least 28 days. 
• The pre-treatment sample must be ≥ 2.0 times the ULN and within 2 weeks before 
starting treatment. 
• The date of response corresponds to the date when the CA125 level is first reduced by 
50%.  
To calculate CA125 responses accurately, the following rules apply:  
1. Intervening samples and the 30-day confirmatory sample must be less than or equal to 
(within an assay variability of 10%) the previous sample. 
2. Variations within the normal range of CA125 levels will not interfere with the response 
definition.  
Timing of CA125 Assessments 
The GCIG recommends that CA125 measurements be taken at specific time intervals: 
• The first sample is collected within 2 weeks before treatment is started. 
• Later samples are collected at intervals of 2 to 4 weeks during treatment and at 
intervals of every 2 or 3 months during follow-up.  
• For each patient, the same assay method must be used, and the assay must be tested in 
a quality-control scheme. Patients are not evaluable by CA125 if they have received 
mouse antibodies or if there has been medical and/or surgical interference with their 
peritoneum or pleura during the previous 28 days.  
This CA125 response definition has been produced to evaluate relapse therapy. If assessing 
therapy that includes two treatment modalities for relapse (eg, surgery and chemotherapy), any 
CA125 response results from both treatments. CA125 cannot distinguish between the effects of 
each treatment. To calculate response rates in protocols, an intent-to-treat analysis should be 
used that includes all patients with an initial CA125 level of at least twice the ULN as eligible 
and evaluable. In addition to calculating response rates in protocols, it is advisable to record 
those patients who have both a CA125 response and whose CA125 level falls to within the 
normal range. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
148 
APPENDIX I. 
RESPONSE DEFINITION (IMMUNE-RELATED RECIST) 
(REGIMEN D ONLY) 
RECIST Version 1.1 will be adapted to account for the unique tumor response characteristics 
seen with treatment with pembrolizumab. Immunotherapeutic agents such as pembrolizumab 
may produce anti-tumor effects by potentiating endogenous cancer-specific immune responses. 
The response patterns seen with such an approach may extend beyond the typical time course of 
responses seen with cytotoxic agents and can manifest a clinical response after an initial increase 
in tumor burden or even the appearance of new lesions. Standard RECIST may not provide an 
accurate response assessment of immunotherapeutic agents such as pembrolizumab; therefore, 
RECIST Version 1.1 will be used with the following adaptations: 
If radiologic imaging indicates PD, tumor assessment should be repeated ≥ 4 weeks later to 
confirm PD, with the option of continuing treatment as described below while awaiting 
radiologic confirmation of progression.  
If repeat imaging shows < 20% tumor burden compared with nadir, stable or improved previous 
new lesion (if identified as cause for initial PD), and stable/improved non-target disease (if 
identified as cause for initial PD), treatment may be continued/resumed.  
If repeat imaging confirms PD due to any of the scenarios list below, patients will be 
discontinued from study therapy (exception noted in Section 5.10.6.4.3).  
In determining whether the tumor burden has increased or decreased, the site study team should 
consider all target lesions and non-target lesions. 
Scenarios where PD is confirmed at repeat imaging: 
• Tumor burden remains ≥ 20% and at least 5 mm absolute increase compared with 
nadir. 
• Non-target disease resulting in initial PD is worse (qualitative). 
• New lesion resulting in initial PD is worse (qualitative). 
• Additional new lesion(s) since last evaluation. 
In patients who have initial evidence of radiologic PD, it is at the discretion of the treating 
physician whether to continue a patient on study treatment until repeat imaging is obtained. This 
clinical judgment decision should be based on the patient’s overall clinical condition, including 
performance status, clinical symptoms, and laboratory data. Patients may receive pembrolizumab 
treatment while waiting for confirmation of PD if they are clinically stable as defined by the 
following criteria: 
• Absence of signs and symptoms indicating PD 
• No decline in ECOG PD 
• Absence of rapid progression of disease 
• Absence of progressive tumor at critical anatomical sites (eg, cord compression) 
requiring urgent alternative medical intervention 
When feasible, patients should not be discontinued until progression is confirmed. This 
allowance to continue treatment despite initial radiologic progression takes into account the 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
149 
observation that some patients can have a transient tumor flare in the first few months after the 
start of immunotherapy, but with subsequent disease response. Patients who are deemed 
clinically unstable are not required to have repeat imaging for confirmation of PD.  
Immune-Related RECIST Assessment of Disease 
Immune-related RECIST is RECIST Version 1.1 adapted as described below to account for the 
unique tumor response seen with immunotherapeutic drugs. Immune-related RECIST will be 
used by the site Investigator/local radiology review to assess tumor response and progression and 
make treatment decisions. These data will be collected in the clinical database.  
Imaging and Treatment After First Radiologic Evidence of Progressive Disease 
 
Clinically Stable 
Clinically Unstable 
Imaging 
Treatment 
Imaging 
Treatment 
First 
radiologic 
evidence of 
PD by 
RECIST 
Version 1.1 
Repeat 
imaging at > 4 
weeks at site 
to confirm PD. 
May continue 
study treatment at 
the local site 
Investigator’s 
discretion while 
awaiting 
confirmatory tumor 
imaging by site by 
irRECIST 
Repeat imaging 
at > 4 weeks to 
confirm PD per 
physician 
discretion only. 
Discontinue treatment. 
Repeat tumor 
imaging 
confirms PD 
by irRECIST 
at the local 
site 
No additional 
imaging 
required 
Discontinue 
treatment 
(exception is 
possible upon 
consultation with 
Sponsor). 
No additional 
imaging 
required 
NA 
Repeat tumor 
imaging 
shows SD, 
PR, or CR by 
irRECIST by 
the local site 
Continue 
regularly 
scheduled 
imaging 
assessments. 
Continue study 
treatment at the 
local site 
Investigator’s 
discretion. 
Continue 
regularly 
scheduled 
imaging 
assessments. 
May restart study treatment if 
condition has improved 
and/or is clinically stable per 
Investigator’s discretion. Next 
tumor image should occur 
according to the every 3 
weeks (XX  ± 7 days) imaging 
schedule for the first year and 
every Y weeks (XX ± 7 days) 
after the first year. 
• In determining whether the tumor burden has increased or decreased, local study site 
investigators should consider all target lesions and non-target lesions (please refer to 
the irRECIST Tip Sheet). Patients who are deemed clinically unstable are not 
required to have repeat tumor imaging for confirmation.  
• For a clinically stable patient with first radiologic evidence of PD by RECIST 
Version 1.1 (ie, unconfirmed progression of disease), it is at the discretion of the 
site investigator to continue treating the patient with the assigned treatment per 
protocol until PD is confirmed at least 28 days after the date of the scan first 
suggesting PD. If radiologic progression is confirmed by subsequent scan, the patient 
will be discontinued from study treatment. If radiologic progression is not confirmed 
by irRECIST per the site, the patient may continue on treatment and follow the 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
150 
regular imaging schedule intervals until progression is confirmed at a later time point 
by the site.  
− NOTE: If a patient has confirmed radiologic progression (ie, 2 scans at least 
4 weeks apart demonstrating PD) per irRECIST, but the patient is achieving a 
clinically meaningful benefit, and there is no further increase in the tumor burden 
at the confirmatory tumor imaging, an exception to continue treatment may be 
considered following consultation with the Sponsor. In this case, if treatment is 
continued, tumor imaging should continue to be performed following the intervals 
outlined in Appendix C. 
• Any patient deemed clinically unstable should be discontinued from study treatment 
at first radiologic evidence of PD and is not required to have repeat imaging for PD 
confirmation. 
• In patients who discontinue study therapy without documented PD, every effort 
should be made to continue monitoring their disease status by tumor imaging using 
the same imaging schedule used while on treatment (every Y weeks (XX days ± 7 
days), until (1) the start of new anti-cancer treatment, (2) PD, (3) death, or (4) the end 
of the study, whichever occurs first. 
The irRECIST data will be collected in the clinical database. 
APPENDIX J. 
CALVERT FORMULA FOR CARBOPLATIN DOSING 
The formula for calculating carboplatin dosage is based upon the patient’s glomerular filtration 
rate (GFR; in mL/min) and carboplatin injection target area AUC (in mg/mL*min). 
Calvert formula for carboplatin dosing: 
Total Dose (mg) = (Target AUC) × (GFR + 25). 
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m². 
Calculations may be based on a patient’s actual body weight subject to appropriate consideration 
of other comorbid conditions; however, GFR should be capped at 125 mL/min for carboplatin 
dosing. For more information regarding carboplatin dosing, please refer to  
https://www.nccn.org/professionals/OrderTemplates/PDF/appendix_B.pdf 
APPENDIX K. 
BODY SURFACE AREA CALCULATION 
To prepare the correct pegylated liposomal doxorubicin doses for administration to each patient, 
the body surface area must be calculated using the following formula or equivalent: 
Body Surface Area (m2) = ([Height {cm} × Weight {kg}] / 3600)½ 
The value calculated will be used to determine the quantity of chemotherapeutic drug to be 
placed in the infusion bag. The weight used for calculation of body surface area should be 
obtained before first treatment and thereafter should be modified only for significant (≥ 10%) 
changes in body weight not influenced by weight gain or loss attributed to fluid retention 
(exceptions may be made for institutional policies).  


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
151 
APPENDIX L. 
ADJUSTED IDEAL BODY WEIGHT CALCULATION 
Adjusted Ideal Body Weight (AIBW) 
IBWa + 0.4 (Actual Weight − IBWa), 
where: 
Ideal Body Weight (IBW) 
IBWa (Male) = 0.9Ha – 88, and 
IBWa (Female) = 0.9Ha – 92. 
a H = height in cm; W = weight in kg. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
152 
APPENDIX M. 
COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS VERSION 4.03 GRADING FOR 
SELECTED ADVERSE EVENTS 
Source: CTCAE Version 4.03, National Cancer Institute, 14 June 2010; NIH Publication No 09-5410. 
Adverse Event 
Grade 
1 
2 
3 
4 
5 
Pneumonitis 
Asymptomatic; clinical or 
diagnostic observations 
only; intervention not 
indicated 
Symptomatic; medical 
intervention indicated; 
limiting instrumental ADL 
Severe symptoms; limiting 
self-care ADL; oxygen 
indicated  
Life-threatening 
respiratory compromise 
Death 
Blurred vision 
Intervention not indicated 
Symptomatic; limiting 
instrumental ADL 
Limiting self-care ADL 
 
- 
Dry eye 
Asymptomatic; clinical or 
diagnostic observations 
only; mild symptoms 
relieved by lubricants 
Symptomatic; multiple 
agents indicated; limiting 
instrumental ADL 
Decrease in visual acuity 
(< 20/40); limiting self-
care ADL 
 
- 
Keratitis 
 
Symptomatic; medical 
intervention indicated (eg, 
topical agents); limiting 
instrumental ADL 
Decline in vision (worse 
than 20/40 but better than 
20/200); limiting self-care 
ADL 
Perforation or blindness 
(20/200 or worse) in the 
affected eye 
- 
Eye disorders – 
other, specify 
Asymptomatic or mild 
symptoms; clinical or 
diagnostic observations 
only; intervention not 
indicated 
Moderate; minimal, local, 
or noninvasive 
intervention indicated; 
limiting age-appropriate 
instrumental ADL 
Severe or medically 
significant but not 
immediately sight-
threatening; 
hospitalization or 
prolongation of existing 
hospitalization indicated; 
disabling; limiting self-
care ADL 
Sight-threatening 
consequences; urgent 
intervention indicated; 
blindness (20/200 or 
worse) in the affected eye 
- 
ADL = activities of daily living. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
153 
APPENDIX N. 
EXAMPLES OF SENSITIVE IN VIVO CYTOCHROME P450 SUBSTRATES AND CYTOCHROME 
P450 SUBSTRATES WITH NARROW THERAPEUTIC RANGE (28 JULY 2011) 
CYP Enzyme 
Sensitive Substrates 
Substrates With Narrow Therapeutic Range 
CYP3A 
Alfentanil, aprepitant, budesonide, buspirone, conivaptan, darifenacin, 
darunavir, dasatinib, dronedarone, eletriptan, eplerenone, everolimus, 
felodipine, indinavir, fluticasone, lopinavir, lovastatin, lurasidone, 
maraviroc, midazolam, nisoldipine, quetiapine, saquinavir, sildenafil, 
simvastatin, sirolimus, tolvaptan, tipranavir, triazolam, vardenafil 
Alfentanil, astemizole, cisapride, cyclosporine, 
dihydroergotamine, ergotamine, fentanyl, 
pimozide, quinidine, sirolimus, tacrolimus, 
terfenadine 
Source: FDA drug development resources. 
http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#classSub. Accessed 09 June 2016. 
APPENDIX O. 
SCHEMA FOR ADMINISTRATION OF STUDY-REQUIRED EYE DROPS 
 
* Lubricating drops are continued if dose is held and/or cycle is delayed. 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Steroid Eye drops – 
6 times daily
Lubricating eye 
drops at least 15 
minutes after steroid 
eye drops – daily as 
directed
Steroid Eye drops – 
4 times daily
Lubricating eye 
drops at least 15 
minutes after steroid 
eye drops – daily as 
directed
Lubricating eye drops  – daily as directed
Cycle Days


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
154 
APPENDIX P. 
HISTORY OF AMENDMENTS 
Amendment 1 Summary of Key Changes 
The primary reasons for amending the protocol were to revise the table for management of 
potential infusion-related reactions, to clarify drugs for premedication before mirvetuximab 
soravtansine infusion, and to add a section for reporting a pregnancy occurring during the study. 
Amendment 1A Summary of Key Changes 
The primary reasons for amending the protocol were to revise inclusion criteria for WCBP, to 
clarify the maximum dose of each drug administered for each regimen and dosing schedule, and 
to add monitoring and management guidelines for peripheral neuropathy.  
The following key changes were made to Amendment 1: 
1. Barrier contraceptive with spermicide and partner’s latex condom were removed from the 
list of acceptable highly effective contraceptive methods. The length of time for the use 
of contraceptives after the last study dose of bevacizumab, carboplatin, or pegylated 
liposomal doxorubicin was changed to 6 months. 
2. The maximum allowable dose of each drug is as follows: mirvetuximab soravtansine 
6.0 mg/kg AIBW every 3 weeks, mirvetuximab soravtansine 6.0 mg/kg every 4 weeks, 
bevacizumab 15 mg/kg every 3 weeks, bevacizumab 10 mg/kg every 2 weeks, 
carboplatin AUC6 every 3 weeks, and pegylated liposomal doxorubicin 50 mg/m2 every 
4 weeks. 
3. Monitoring and management guidelines for peripheral neuropathy were added to 
Section 5.9. 
Amendment 1B Summary of Key Changes 
The primary reasons for amending the protocol were to correct discrepancies between sections of 
the protocol and the Schedules of Clinical Assessments in the appendices and to clarify study 
assessments. 
The following key changes were made in Amendment 1B: 
1. The PK and immunogenicity section (Section 6) was updated to provide additional clarity 
on the time points for PK and immunogenicity sample collection.  
2. The vital signs and ECG sections (Section 8.6 and Section 8.7) were updated to provide 
additional clarity on time points. 
3. Study activities (Section 10) were updated. Most of the section was removed because this 
information is included in the Schedules of Clinical Assessments in the appendices. 
Information regarding screening, end of treatment, and follow-up visits remains in the 
section. 
4. The Schedules of Clinical Assessments and pharmacokinetics (Appendix A, Appendix B, 
Appendix C, and Appendix D) were updated to correct discrepancies with the protocol 
text.   


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
155 
Amendment 2 Summary of Key Changes 
The primary reasons for amending the protocol were to add Regimen D, to revise the time period 
for reporting AEs, and to clarify PK time points.  
The following key changes were made to Amendment 1A: 
1. Regimen D was added to the protocol. This regimen is mirvetuximab soravtansine in 
combination with pembrolizumab. The entire protocol was updated to include this 
regimen. There is a Dose Escalation part and a Dose Expansion for Regimen D.  
2. The time period for reporting AEs and SAEs was updated. In this amendment, AEs and 
SAEs regardless of causality are recorded and reported from the time of informed consent 
until at least 30 days after the last dose of study medication. 
3. The PK section (Section 6.1) was updated to clarify the timing of PK sample collection 
for each drug administered. The blood collection schedule was updated to separate each 
drug.  
4. Adverse events of special interest were added. 
5. Overdose information for pembrolizumab was added. 
6. The concomitant medications section was updated to include medications metabolized by 
CYP3A, vaccines (Regimen D only), and systemic steroids (Regimen D only). 
7. Typographical errors were corrected. 
Amendment 3 Summary of Key Changes 
The primary reasons for amending the protocol were to add prophylactic corticosteroid eye 
drops, to modify the inclusion criteria for prior therapies, and to clarify management guidelines 
for ocular AEs. 
1. The premedication section (Section 5.8.1) was updated to include prophylactic 
corticosteroid eye drops. A schema for the administration schedule for eye drops was 
added (Appendix O). Additionally, information about lubricating eye drops was moved 
from the concomitant medication section (Section 5.13) to the premedication section 
(Section 5.8.1). 
2. Inclusion criteria to define the therapies considered to be prior therapies were modified. 
3. Inclusion criteria for prior therapies for Regimen A Dose Expansion were changed. 
4. Exclusion criterion 12 for all patients was revised to specify that patients with a history of 
non-infectious pneumonitis that required steroids or who have current pneumonitis will 
be excluded. 
5. Exclusion criterion 14 was updated to add that patients with severe hypersensitivity 
(≥ Grade 3) to pembrolizumab and/or any of its excipients will be excluded. 
6. The ocular management guidelines were updated for clarification. 
7. Discontinuation criterion for carboplatin to allow for discontinuation of carboplatin after 
6 cycles at the discretion of the Investigator was added. 
8. Dose modification guidelines for bevacizumab were updated. 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
156 
9. The AE section was updated to provide further clarification. 
10. The section for patient informed consent was updated for clarification. 
11. Typographical errors were corrected. 
Amendment 4 Summary of Key Changes 
The primary reason for this amendment was to add a cohort of patients with EOC, primary 
peritoneal cancer, or fallopian tube cancer who will receive a triplet dosing regimen of 
mirvetuximab soravtansine + carboplatin + bevacizumab. The amendment also enabled early 
closure, due to slow enrollment, of the bevacizumab-naïve cohort (Cohort 1) and removal of 
Regimen A Expansion Cohort 3 (endometrial cancer).  
1. The protocol was updated for the new triplet cohort: The study title was updated to reflect 
the new scope of the study; a rationale for the triplet cohort was added to Section 1.10; 
the study objectives and endpoints were updated (Section 2); the number of patients, 
study design, and study schema were adjusted and new eligibility criteria added 
(Section 3 and Section 4); PK sample collections were added (Section 6); and the 
statistical analysis was updated (Section 11). 
2. The number of patients to be recruited into Expansion Cohort 1 was adjusted from 
35 bevacizumab-naïve patients to approximately 20 bevacizumab-naïve patients 
(Section 4.1.5), and the statistical analysis was updated (Section 11). 
3. Clarified the procedures for tumor sample collections including the timing of the 
collection, and a window for the Cycle 2 Day 8 sample was added (Section 7.1.1 and 
Section 8.17). 
4. Removed the Endometrial Expansion Cohort 3. This change was made throughout the 
protocol. 
5. The patient FRα status for patients enrolled into the Expansion Cohorts was increased 
from FRα ≥ 25% to FRα ≥ 50% of tumor staining at ≥ 2 + intensity. This change was 
primarily made in the inclusion criteria (Section 3.1.2). 
6. Reduced the scan frequency for patients receiving Regimen A and Regimen B, after they 
have been receiving study drug for 24 weeks, from every 6 weeks to every 12 weeks, and 
then reduced the frequency further to every 3 months for patients who remain on study 
for more than one year from randomization. 
7. Provided greater clarity around the definition of platinum sensitive in the inclusion 
criteria for Regimens B and E (Section 3.1.1.2). 
8. Updated the background information on pembrolizumab (Section 1.5.1 and Appendix E).  
9. Updated the dose modification guidelines for pembrolizumab (Section 5.10.4.5). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
157 
Amendment 5 Summary of Key Changes 
The primary reason for this amendment was to add an additional cohort (Cohort 3) to 
Regimen A, which will include patients with one to three prior therapies who may be either 
platinum resistant or platinum sensitive, and who may or may not have received prior therapy 
with bevacizumab. Further, the amendment includes the change of the investigational product 
name from IMGN853 to the International Non-proprietary Name of mirvetuximab soravtansine. 
The amendment also removed the alternative dosage schedule for Regimen A because it was not 
enrolled. 
1. The protocol was updated to reflect a new Cohort (Cohort 3) in Regimen A based on 
clinical experience with Regimen A Cohorts 1 and 2. This includes the study title (Phase 
1b/2), rationale for the new Cohort (Section 1.10), Study Objectives and Endpoints 
(Section 2), Study Population/Inclusion and Exclusion Criteria (Section 3), Study 
Overview and Schema (including diagram) (Section 4.1.1), and Sample Size 
(Section 11.1). 
2. The alternative dosing schedule for Regimen A was removed because this schedule did 
not enroll. Text was removed from (Section 4.1.3.1), and Table 2 and Appendix C were 
deleted. 
3. The AIBW justification was removed for calculating the mirvetuximab soravtansine dose 
because the use of AIBW is now established and no longer needs justification 
(Section 5.8.4.1, Appendix L, and Appendix K). 
4. The mirvetuximab soravtansine administration section was amended to include a special 
note to ensure that mirvetuximab soravtansine is administered first when used in 
combination with other study treatments (Section 5.8.4.3). 
5. Monitoring of Ocular disorders was updated for safety information guidelines and 
clarification around study visits (Section 5.9.2.1 and Table 8). 
6. Monitoring of Non-infectious Pneumonitis was updated for safety information guidelines 
(Section 5.9.3 and Table 11). 
7. Re-treatment criteria were updated to reflect specifications for Regimen E 
(Section 5.10.1). 
8. Pregnancy testing after study discontinuation after a CR was updated 
(Section 5.10.6.4.2). 
9. Myocarditis was added as an AE that would cause discontinuation from pembrolizumab 
(Section 5.10.6.4.4 and Table 25). 
10. Guidelines on reporting an overdose from any study treatment were updated 
(Section 5.1.4.1). 
11. The methodology used to assess the tumor FRα expression levels was defined and 
updated (Section 7.1.1). 
12. The Potential Markers of Drug Resistance section was updated to align with objectives 
and endpoints and to improve overall clarity (Section 7.2.1). 


mirvetuximab soravtansine 
Amendment 5 
Clinical Study Protocol IMGN853-0402 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
158 
13. Eligibility based on FRα expression was updated to provide clear guidance on the 
methods used, and Regimen A Cohort 3 was added to this section (Section 8.16). 
14. The safety sections were updated for consistency with program and ImmunoGen 
standards (Section 9.1, Section 9.1.1.1, Section 9.1.1.2, Table 29, Section 9.1.1.3, 
Section 9.2.1, and Section 9.2.4). 
15. The sample size section was updated for the new cohort and to provide better clarity 
around patient numbers in Regimens D and E (Section 11.1). 
16. The PK section was updated to include a description of the analysis of the PK samples, 
including the substances to be analyzed and indication of the parameters to be calculated 
from the analysis (Section 11.2). 
17. The immunogenicity analysis section was updated to improve clarity around the 
calculation of ADA-positive results (Section 11.3). 
18. The patient confidentiality section was updated to provide details on protected health 
information and Investigator responsibilities (Section 13.5). 
19. The study procedures section and the Schedule of Clinical Assessment tables were 
aligned and streamlined for internal consistency. Associated footnotes were amended and 
updated (Section 8, Appendix A, Appendix B, and Appendix C). 

SAP_001.pdf: 
ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
1 
ImmunoGen, Inc. 
Protocol #: 0402 
A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab 
Soravtansine (IMGN853) in Combination with Bevacizumab, Carboplatin, Pegylated Liposomal 
Doxorubicin, Pembrolizumab, or Bevacizumab + Carboplatin, in Adults with Folate Receptor Alpha 
Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer 
Statistical Analysis Plan 
Version 2.0 
Document last saved: 3-Aug-2020 12:01 PM 
Prepared for: 
 
ImmunoGen, Inc. 
830 Winter Street 
Waltham, MA 02451 
Prepared by: 
 
IQVIA Biotech 
1700 Perimeter Park Dr. 
Morrisville, NC 27560 
Approvals 
Aug 3, 2020 | 2:44:58 PM EDT 
Date 
Aug 3, 2020 | 2:56:22 PM EDT 
Date 
Aug 3, 2020 | 2:44:58 PM EDT 
Date 
NCT #NCT02606305


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
2 
 
 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ......................................................................................................... 6 
1. 
INTRODUCTION ....................................................................................................... 9 
1.1. 
Background .................................................................................................................. 9 
2. 
PROTOCOL OBJECTIVES ...................................................................................... 11 
2.1. 
Primary Objectives .....................................................................................................11 
2.1.1. 
Dose Escalation...........................................................................................................11 
2.1.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) ................................11 
2.2. 
Secondary Objectives................................................................................................. 11 
2.3. 
Exploratory Objectives .............................................................................................. 12 
3. 
STUDY ENDPOINTS ................................................................................................12 
3.1. 
Primary Endpoints ..................................................................................................... 12 
3.1.1. 
Dose Escalation (Regimens A, B, C, and D) ............................................................. 12 
3.1.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) ................................12 
3.2. 
Secondary Endpoints ................................................................................................. 12 
3.3. 
Exploratory Endpoints ................................................................................................13 
4. 
STUDY DESIGN ...................................................................................................... 14 
4.1. 
Design Overview ....................................................................................................... 14 
4.1.1. 
Cohort Review Committee .........................................................................................15 
4.1.2. 
Dose Escalation Phase ............................................................................................... 15 
4.1.3. 
Dose Expansion Phase ............................................................................................... 18 
4.1.4. 
Triplet Dose Cohort (Regimen E) ............................................................................... 19 
4.1.5. 
Second Course Phase for Regimen D (Mirvetuximab Soravtansine + 
Pembrolizumab) ......................................................................................................... 19 
4.2. 
Study Period Schema ................................................................................................. 21 
4.3. 
Study Population ........................................................................................................ 21 
4.3.1. 
Enrolled Patient and Screen Failure Definitions ........................................................ 21 
4.4. 
Sample Size Predictions ............................................................................................. 22 
4.4.1. 
Dose Escalation...........................................................................................................22 
4.4.2. 
Dose Expansion ......................................................................................................... 22 
4.4.3. 
Overall ....................................................................................................................... 24 
4.5. 
Treatment Randomization.......................................................................................... 24 
4.6. 
Assessment Schedule ................................................................................................. 24 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
3 
 
 
5. 
INTERVENTIONS .................................................................................................... 25 
5.1. 
Clinical Trial Material ................................................................................................25 
6. 
GENERAL ANALYTICAL CONSIDERATIONS .................................................. 25 
6.1. 
Data Sources .............................................................................................................. 25 
6.2. 
Definition of Baseline ................................................................................................ 25 
6.3. 
Missing Data .............................................................................................................. 26 
6.4. 
Multiple Assessments for the Same Assessment Time Point .....................................27 
6.5. 
Multiple Study Centers ...............................................................................................27 
6.6. 
Covariate Adjustment in Primary Analysis ................................................................27 
6.7. 
Sample Size Reassessment .........................................................................................27 
6.8. 
Interim Analyses or Timing of Analyses ................................................................... 27 
6.9. 
Test Sizes ................................................................................................................... 27 
6.10. 
Multiple Comparisons ................................................................................................27 
6.11. 
Analysis Populations.................................................................................................. 27 
6.11.1 
Screened ..................................................................................................................... 28 
6.11.2 
Safety Population ....................................................................................................... 28 
6.11.3 
Response-Evaluable Population ................................................................................ 28 
6.11.4 
CA125 Evaluable Population .....................................................................................28 
6.12. 
Data Display Characteristics ...................................................................................... 28 
7. 
PATIENT ACCOUNTABILITY .............................................................................. 29 
7.1. 
Patient Characteristics................................................................................................ 29 
7.2. 
Patient Disposition ..................................................................................................... 31 
7.2.1 
Screened Patients ....................................................................................................... 31 
7.2.2 
Safety Population ....................................................................................................... 31 
7.3. 
Protocol Deviations and Population Inclusions ......................................................... 31 
8. 
EFFICACY ANALYSES .......................................................................................... 32 
8.1. 
Efficacy Outcomes ......................................................................................................32 
8.2. 
Primary Efficacy Outcome Analysis ......................................................................... 35 
8.3. 
Secondary Efficacy Analyses .................................................................................... 35 
8.4. 
Exploratory Efficacy Analyses ...................................................................................36 
8.5. 
Efficacy Analysis on Subgroups of Patients .............................................................. 36 
8.6. 
Sensitivity Analyses ....................................................................................................37 
8.7. 
Other Efficacy-related Summaries ..............................................................................37 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
4 
 
 
9. 
SAFETY ANALYSES .............................................................................................. 37 
9.1. 
Exposure .................................................................................................................... 37 
9.2. 
Adverse Events .......................................................................................................... 38 
9.3. 
Dose Limiting Toxicities (DLTs) ...............................................................................41 
9.4. 
Clinical Laboratory Results ........................................................................................41 
9.5. 
Vital Signs.................................................................................................................. 43 
9.6. 
Electrocardiograms (ECGs) ........................................................................................43 
9.7. 
Concomitant Medications (CMs) ...............................................................................43 
9.8. 
Concomitant Procedures .............................................................................................44 
9.9. 
Ophthalmic Examinations .......................................................................................... 44 
9.10. 
Ocular Symptom Assessments................................................................................... 45 
9.11. 
Corticosteroid and Lubricating Eye Drop Compliance ..............................................45 
9.12. 
Transfusions ................................................................................................................45 
9.13. 
Physical Examination .................................................................................................45 
9.14. 
Pulmonary Function Tests ......................................................................................... 45 
9.15. 
Pulse Oximetry .......................................................................................................... 45 
9.16. 
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ................... 45 
9.17. 
ECHO/MUGA ............................................................................................................45 
9.18. 
24 Hour Urine Protein................................................................................................ 45 
10. 
IMMUNOGENICITY ............................................................................................... 45 
11. 
BIOMARKERS ..........................................................................................................46 
12. 
PHARMACOKINETICS .......................................................................................... 46 
REFERENCES ............................................................................................................................. 47 
APPENDIX 1: TEMPLATE SAS® CODE....................................................................................48 
 
LIST OF TABLES 
Table 1: 
History of Protocol Amendments .............................................................................. 10 
Table 2: 
Planned Dose Levels (Dose Escalation) for Regimen A (Mirvetuximab 
Soravtansine + Bevacizumab) ................................................................................... 16 
Table 3: 
Planned Dose Levels (Dose Escalation) for Regimen B (Mirvetuximab 
Soravtansine + Carboplatin) ...................................................................................... 17 
Table 4: 
Planned Dose Levels (Dose Escalation) for Regimen C (Mirvetuximab 
Soravtansine + Pegylated Liposomal Doxorubicin) .................................................. 17 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
5 
 
 
Table 5: 
Planned Dose Levels (Dose Escalation) for Regimen D (Mirvetuximab 
Soravtansine + Pembrolizumab) ................................................................................ 18 
Table 6: 
Planned Doses Triplet Cohort Regimen E (Mirvetuximab Soravtansine + 
Bevacizumab + Carboplatin) ..................................................................................... 19 
Table 7: 
Confidence Interval (90%) for True ORR with Sample Size = 60 ............................ 23 
Table 8: 
Confidence Interval (90%) for True ORR with Sample Size = 35 ............................ 24 
Table 9: 
Confidence Interval (90%) for True ORR with Sample Size = 40 ............................ 24 
Table 10: PFS Definitions (includes investigator assessed radiographic progression 
only) ........................................................................................................................... 33 
Table 11: Summary of Efficacy Analysis ...................................................................................34 
LIST OF FIGURES 
Figure 1: 
Study Design Schema ................................................................................................ 15 
Figure 2: 
Study Period Schema ................................................................................................. 21 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
6 
 
 
LIST OF ABBREVIATIONS 
 
Abbreviation or Specialist Term 
Explanation 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
AIBW 
Adjusted ideal body weight 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AUC 
Area under the time-concentration curve 
BOR 
Best Overall Response 
BRCA 
Breast cancer susceptibility gene 
BSA 
Body Surface Area 
CA125 
Cancer antigen 125 
Cl 
Clearance 
CM 
Concomitant medication 
Cmax 
Maximum plasma concentration 
CP 
Concomitant procedure 
CR 
Complete response/remission 
CRC 
Cohort Review Committee 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of Variation 
DCR 
Disease Control Rate 
DLT 
Dose limiting toxicity 
DM4 
N2’-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-sulfopentyl]- 
N2’-deacetylmaytansine 
DM4-Me 
Methylated N2’-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2- 
sulfopentyl]-N2’-deacetylmaytansine 
DOR 
Duration of response 
ECG 
Electrocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
eCRF 
Electronic case report form 
EOC 
Epithelial Ovarian Cancer 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
7 
 
 
 
Abbreviation or Specialist Term 
Explanation 
FcγR 
Fc gamma receptor 
FIH 
First in human 
FRα 
Folate receptor α 
GCIG 
Gynecologic Cancer Intergroup 
IEC 
Independent ethics committee 
IHC 
Immunohistochemistry 
IMGN 
ImmunoGen 
IRB 
Institutional review board 
irRECIST 
Immune-related Response Evaluation Criteria in Solid Tumors 
MDR1 
Multi-drug resistent gene 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
Maximum tolerated dose 
MUGA scan 
Multigated Acquisition scan 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PARP 
Poly (ADP-ribose) polymerase 
PD 
Progressive Disease 
PD-1 
Programmed death receptor-1 
PFS 
Progression-free Survival 
Pgp 
P-Glycoprotein 
PK 
Pharmacokinetics 
PR 
Partial Response/remission 
PT 
Preferred Term (MedDRA terminology) 
Q3W 
Every 3 weeks 
Q4W 
Every 4 weeks 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended Phase 2 Dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SCP 
Second Course Phase 
SD 
Stable Disease 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
8 
 
 
 
Abbreviation or Specialist Term 
Explanation 
SOC 
System Organ Classification (MedDRA terminology) 
t1/2(β) 
Terminal Half-life 
TBL 
Total Bilirubin 
TEAE 
Treatment Emergent Adverse Events 
Tmax 
Time to maximum plasma concentration 
TTR 
Time to Response 
ULN 
Upper Limit of Normal 
VSS 
Volume of distribution at steady state 
WCBP 
Woman of childbearing potential 
WHO-DD 
World Health Organization –Drug Dictionary 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
9 
 
 
1. 
INTRODUCTION 
1.1. 
Background 
In the first-in-human (FIH) Phase 1 study (Study IMGN853-0401) of single-agent mirvetuximab 
soravtansine, objective responses have been observed in patients with heavily pretreated FRα 
positive EOC and endometrial cancer. As of 29 April 2016, mirvetuximab soravtansine has a 
26% confirmed overall response rate (95% CI 14%, 41%) and median PFS (mPFS) 4.8 months 
(95% CI 3.9, 5.7 months) in the 46 patients with platinum-resistant EOC in the patient expansion 
cohort in study IMGN853-0401 (Moore 2016). The confirmed overall response rate is 44% (95% 
CI 20%, 70%) and the median PFS (mPFS) is 6.7 months (95% CI 3.9, 11 months) in the subset 
of 16 patients with FRα−positive (medium/high expression) platinum-resistant EOC with one to 
three prior regimens treated as part of a 46 patient expansion cohort in study IMGN853-0401 
(Moore 2016). Adverse events occurring in > 20% of patients in this cohort included diarrhea, 
blurred vision, fatigue, nausea, vomiting, and peripheral neuropathy, and were mostly low grade. 
Blurred vision is likely related to corneal keratopathy, transient microcysts that form on the 
cornea, causing temporary astigmatism. 
Bevacizumab carboplatin and pegylated liposomal doxorubicin are currently in use for the 
treatment of EOC. Doublet combinations of mirvetuximab soravtansine with bevacizumab, 
carboplatin, and pegylated liposomal doxorubicin have all demonstrated additive activity in 
preclinical models. Pembrolizumab, an anti-programmed death receptor-1 (PD-1), monoclonal 
antibody is approved for the treatment of melanoma and non-small cell lung cancer and has 
shown preliminary anti-tumor activity as a single agent in EOC (Varga 2015). 
The current study is designed to establish the maximum tolerated dose (MTD) and determine the 
recommended Phase 2 dose (RP2D) of mirvetuximab soravtansine when administered in 
combination with either bevacizumab, carboplatin, pegylated liposomal doxorubicin, or 
pembrolizumab. The study will also investigate activity signals, and safety and tolerability of a 
triplet dose regimen of mirvetuximab soravtansine + bevacizumab + carboplatin. All study 
treatments will be administered intravenously to adult patients with FRα positive ovarian cancer, 
primary peritoneal cancer, or fallopian tube cancer. The safety, tolerability, immunogenicity of 
mirvetuximab soravtansine, and preliminary anti-tumor activity of mirvetuximab soravtansine in 
combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin, pembrolizumab, 
or bevacizumab + carboplatin will be characterized. The pharmacokinetics (PK) of mirvetuximab 
soravtansine, bevacizumab, carboplatin and pegylated liposomal doxorubicin will be 
characterized. PK profile of pembrolizumab may be characterized, if warranted, due to a safety 
signal. 
The protocol for Study 0402 describes the general approach to analysis of data from the study. 
This analysis plan describes additional detail needed to complete such an analysis. Table, figure 
and listing shells will be supplied in an accompanying document. 
This Statistical Analysis Plan (SAP) is based on Amendment 5 of Protocol IMGN853-0402. 
A brief history of protocol amendments is presented in Table 1. 
This SAP will govern the analysis of data from this study. The plan may be modified until time 
of database lock. Any deviations from the analysis plan will be documented as such in the study 
report. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
10 
 
 
Table 1: 
History of Protocol Amendments 
 
Version 
Approval Date 
Salient Changes, if any* 
Protocol 
11 August 2015 
Amendment 1 
23 September 2015 
No changes that require accommodation in this analysis 
plan. 
Amendment 1A 
11 February 2016 
No changes that require accommodation in this analysis 
plan. 
Amendment 1B 
13 May 2016 
No changes that require accommodation in this analysis 
plan. 
Amendment 2 
21 June 2016 
Regimen D was added to the protocol. This regimen is 
mirvetuximab soravtansine in combination with 
pembrolizumab. The entire protocol was updated to 
include this regimen. There is a dose escalation part and a 
dose expansion for Regimen D. 
The time period for reporting AEs and SAEs was updated. 
In this amendment, Aes and SAEs regardless of causality 
are recorded and reported from the time of informed 
consent until at least 30 days after the last dose of study 
medication. 
Adverse events of special interest were added. 
Amendment 3 
26 June 2017 
The exploratory endpoint regarding BRCA testing was 
removed. The endpoint for analysis of tumor infiltrating 
cells by IHC was clarified. 
The secondary objective and endpoint sections were 
updated to specify that the objective response rate analysis 
is to be performed for the dose escalation cohorts for all 
regimens, plus the dose expansion cohort 3 for Regimen A. 
Hormonal therapy was added as a prior therapy. 
Prophylactic corticosteroid eye drops and lubricating eye 
drops were added as required pretreatments. 
Amendment 4 
14 November 2017 
Regimen E was added to the protocol. This regimen is 
mirvetuximab soravtansine in combination with 
bevacizumab and carboplatin. The entire protocol was 
updated to include this regimen. 
Endometrial cancer cohort (Regimen A, Cohort 3) was 
removed. The entire protocol was updated to remove this 
cohort in the dose-expansion phase. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
11 
 
 
Table 1: 
History of Protocol Amendments (Continued) 
 
Version 
Approval Date 
Salient Changes, if any* 
Amendment 5 
21 September 2018 
Added an additional cohort (Cohort 3) to Regimen A, 
which will include patients with one to three prior 
therapies who may be either platinum resistant or platinum 
sensitive, and who may or may not have received prior 
therapy with bevacizumab. 
Changed the investigational product name from IMGN853 
to the International Non-proprietary name of mirvetuximab 
soravtansine. 
Removed the alternative dosage schedule for Regimen A 
because it was not enrolled. 
* Changes expected to require accommodation in analysis plan. 
 
2. 
PROTOCOL OBJECTIVES 
All objectives apply to all dosing regimens and all cohorts unless otherwise noted. 
 
2.1. 
Primary Objectives 
The protocol lists the following primary objectives: 
 
2.1.1. 
Dose Escalation 
Evaluate the safety and tolerability of mirvetuximab soravtansine when given in combination 
with bevacizumab, carboplatin, pegylated liposomal doxorubicin, or pembrolizumab (Regimens 
A, B, C, and D, respectively) in patients with EOC, primary peritoneal cancer, or fallopian tube 
cancer. 
 
2.1.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) 
Assess preliminary response-based anti-tumor activity of mirvetuximab soravtansine when 
administered in combination with bevacizumab (Regimen A) or pembrolizumab (Regimen D) 
and in combination with bevacizumab and carboplatin (Regimen E) in patients with EOC, 
primary peritoneal cancer, or fallopian tube cancer. 
 
2.2. 
Secondary Objectives 
The protocol lists the following secondary objectives: 
• Evaluate the safety and tolerability of mirvetuximab soravtansine when administered 
in combination with bevacizumab or pembrolizumab (Dose Expansion, Regimens A 
and D, respectively) and in combination with bevacizumab and carboplatin (Regimen 
E [Triplet]) in patients with EOC, primary peritoneal cancer, or fallopian tube cancer 
• Assess preliminary response-based anti-tumor activity of the combination Regimens 
(Dose Escalation, Regimens A through D) 
• Assess PFS 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
12 
 
 
• Measure duration of response (DOR): the time from first objective response (CR/PR) 
to the time of progressive disease (PD) among those who have achieved a PR or CR 
• Assess Gynecologic Cancer Intergroup (GCIG) CA125 response rate of the 
combination regimens 
• Characterize PK of mirvetuximab soravtansine when used in combination regimens 
• Evaluate bevacizumab, carboplatin, and pegylated liposomal doxorubicin 
concentrations when administered in combination with mirvetuximab soravtansine 
• Characterize immunogenicity of mirvetuximab soravtansine 
2.3. 
Exploratory Objectives 
The protocol lists the following exploratory objectives: 
• Assess any association between FRα expression levels and clinical response 
• Identify or evaluate potential biomarkers in blood and tumor tissue that might predict 
response to each of the four combinations 
• Evaluate pembrolizumab concentrations if warranted by a safety signal (Regimen D 
only) 
• Assess anti-tumor activity of the combination with pembrolizumab per immune- 
related RECIST (irRECIST) (Regimen D only) 
 
3. 
STUDY ENDPOINTS 
3.1. 
Primary Endpoints 
The protocol lists the following primary endpoints: 
 
3.1.1. 
Dose Escalation (Regimens A, B, C, and D) 
• Treatment-emergent adverse events, laboratory test results, physical examination, 
electrocardiograms (ECGs), and vital signs. 
 
3.1.2. 
Dose Expansion (Regimens A and D) and Regimen E (Triplet) 
• Objective response rate, defined as percentage of patients with confirmed response 
(complete response/remission [CR] + partial response/remission [PR]) as assessed by 
Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 
 
3.2. 
Secondary Endpoints 
The protocol lists the following as secondary endpoints: 
• Treatment-emergent AEs, changes in laboratory test results, physical examination, 
ECGs, and vital signs (Dose Expansion [Regimens A and D] and Regimen E 
[Triplet]) 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
13 
 
 
• Objective response rate, defined as percentage of patients with confirmed response 
(CR + PR) as assessed by RECIST Version 1.1 (Dose Escalation, Regimens A 
through D) 
• Progression-free survival, defined as the time from first dose to PD or death, 
whichever occurs first 
• Duration of response, defined as the time from first objective response (CR/PR) to the 
time of PD among those who have achieved a PR or CR 
• Number of patients with GCIG CA125 criteria clinical responses 
• Mirvetuximab soravtansine PK parameters for intact ADC, total antibody, DM4, and 
S-methyl DM4 include, but are not limited to, Cycle 1 and Cycle 3 maximum plasma 
concentration (Cmax), area under the time-concentration curve (AUC), terminal 
halflife (t½), clearance (CL), volume of distribution at steady state (Vss), and time 
that Cmax occurs (tmax) 
• Concentration data of bevacizumab, carboplatin, and pegylated liposomal 
doxorubicin will be measured before and after bevacizumab, carboplatin, and 
pegylated liposomal doxorubicin infusions (Cycle 1 through Cycle 6) 
• Immunogenicity: presence of anti-drug antibodies (ADA) to mirvetuximab 
soravtansine 
 
3.3. 
Exploratory Endpoints 
The protocol lists the following exploratory endpoints. 
• Correlation of FRα expression, by IHC (protein), quantitative reverse 
transcriptasepolymerasechain reaction (mRNA), or other quantitative methods, to 
clinical endpoints 
• Measure biomarkers in blood and tumor tissue including, but not limited to, 
mutational and genomic alterations of tumor samples; expression and activation of 
oncogenic genes and pathways in tumor samples; expression and polymorphism of 
drug transporters such as multidrug resistance protein-1 (p-glycoprotein [PgP]); the 
genotype of FcγR; expression and of immune-related genes and gene signatures 
(Regimen D only), and infiltration of tumor-related immune cells (Regimen D only) 
• Concentration data for pembrolizumab if warranted by a safety signal (Regimen D 
only) 
• Evaluate efficacy endpoints per irRECIST (Appendix I) (Regimen D only) 
− Progression-free survival, ORR, and DOR per irRECIST are defined as specified 
for the respective endpoints using RECIST Version 1.1 above, except that a 
confirmation assessment of PD (at least 4 weeks after the initial PD assessment) is 
required for patients who remain on treatment after documented PD per RECIST 
Version 1.1. Patients who discontinue treatment after documented PD assessment 
per RECIST Version 1.1 will be counted as having PD on the date of the 
documented PD assessment. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
14 
 
 
Note: Unless specifically warranted by relevance to safety or efficacy endpoints, the exploratory 
endpoints will not be reported in the clinical study report. 
 
4. 
STUDY DESIGN 
4.1. 
Design Overview 
This is an open label, Phase 1b/2, non-randomized combination study of mirvetuximab 
soravtansine with bevacizumab, carboplatin, pegylated liposomal doxorubicin, pembrolizumab, 
or bevacizumab + carboplatin in adult patients with FRα−positive advanced EOC, primary 
peritoneal cancer, or fallopian tube cancer. 
This Phase 1b/2 study comprises a dose escalation phase followed by an MTD expansion phase 
to further characterize the safety profile and confirm the MTD as the RP2D (Figure 1). A triplet 
Regimen (Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin) will be opened 
to evaluate the safety and toleratiblity and to assess any early signs of activity in patients dosed 
with the combination regimen. 
The dose escalation phase will follow a standard 3+3 cohort design. The MTD will be 
determined from the assessment of Dose Limiting Toxicities (DLTs) during the first treatment 
cycle (see Protocol Table 5). A dose expansion phase is planned for Regimen A (mirvetuximab 
soravtansine + bevacizumab) and Regimen D (mirvetuximab soravtansine + pembrolizumab) 
and will open pending sponsor decision; patients enrolled in the dose expansion phase will 
receive study treatment at the MTD or RP2D determined during the dose escalation (Figure 1). 
For Regimen A, patients in the dose expansion phase may be enrolled according to prior 
exposure to bevacizumab and disease diagnosis into three dose expansion cohorts as follows: 1) 
Dose Expansion Cohort 1: bevacizumab naïve; 2) Dose Expansion Cohort 2: bevacizumab 
pretreated; and 3) Dose Expansion Cohort 3: one to three prior treatments, one of which could 
have been bevacizumab (Figure 1). Regimen E (Triplet Cohort) will be opened because 
enrollment and safety from Regimen A and B have been established, and Regimen A (Dose 
Expansion Cohorts) enrollment is currently ongoing. The planned doses for patients receiving 
the triplet dose (Regimen E) were derived from all available data in Regimens A and B. 
Regimen E may enroll approximately 40 patients, with a plan to be dosed at the maximum dose 
level determined to be safe. 
Safety and tolerability will be assessed on an ongoing basis, and patients will be enrolled initially 
in a stepwise manner. 
The period of observation extends from the time the patient receives the first dose of study 
treatment (mirvetuximab soravtansine and/or combination agent) until the final follow-up study 
visit. Patients will continue to receive mirvetuximab soravtansine and/or the combination agent 
until progressive disease (PD); unacceptable toxicity or withdrawal of consent, whichever comes 
first; or until the Sponsor terminates the study. Patients who experience PD, as defined by 
RECIST, while on study may remain on study, provided there is evidence of clinical benefit and 
no unacceptable toxicity, as agreed upon by the Investigator and the Medical Monitor. 
Pembrolizumab (Regimen D) will be continued for up to 2 years. Patients who discontinue study 
treatment for reasons other than PD will be followed until PD; start of new anti-cancer therapy; 
or death, whichever occurs first. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
15 
 
 
Figure 1: 
Study Design Schema 
 
a Enrolled 46 patients to ensure 35 patients with medium and high FRα expression and 11 patients with low FRα 
expression 
b Enroll approximately 50 patients to evaluate 40 patients at the MTD. 
 
4.1.1. 
Cohort Review Committee 
The Cohort Review Committee (CRC) is comprised of the ImmunoGen Medical Monitor and 
Investigators from participating sites. Once the last patient in a given cohort has completed a 
cycle of study treatment, a CRC meeting will be convened to review all safety data and decide 
whether to continue or halt dose escalation, further expand individual dose levels to gain 
additional safety data, or explore lower or intermediate dose levels. In addition to meeting to 
review safety data at the end of each dose level, the CRC will convene to review safety data for 
ongoing patients and patients in follow-up as per the cohort management plan. 
 
4.1.2. 
Dose Escalation Phase 
The primary aim of the dose escalation phase for each Regimen is to evaluate the safety and 
tolerability of mirvetuximab soravtansine in combination with bevacizumab, carboplatin, 
pegylated liposomal doxorubicin or pembrolizumab, to identify the MTD and RP2D, and to 
characterize the PK profile of mirvetuximab soravtansine, bevacizumab, carboplatin and 
pegylated liposomal doxorubicin. The PK profile of pembrolizumab may be characterized if 
warranted due to a safety signal. 
Patients will be enrolled in cohorts of 3 to 6 patients until the MTD for each of the four regimens 
is defined. If a patient is eligible for more than one combination regimen, the investigator will 
assign the patient to the most appropriate combination regimen, taking into consideration the 
patient’s disease history, treatment history, and/or preferences. Approximately 16 (Regimen A), 
22 (Regimen B), 22 (Regimen C) and 16 (Regimen D) patients will be enrolled in each regimen, 
plus additional 10 patients in each arm to define the MTD. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
16 
 
 
The starting dose of mirvetuximab soravtansine will be 5 mg/kg, with the dose calculated using 
adjusted ideal body weight (AIBW). The four regimens will be evaluated in parallel and 
independently. 
The treatment regimens and planned dose levels for the dose escalation phase of the study are 
outlined below and in Table 2, Table 3, Table 4, and Table 5. 
Intermediate or lower dose levels of pegylated liposomal doxorubicin, bevacizumab, or 
carboplatin may be explored if DLTs can be attributed to their mechanism of action. Higher 
doses of pegylated liposomal doxorubicin (up to 50 mg/m2) and carboplatin (AUC 6) may also 
be considered. 
Regimen A: Mirvetuximab soravtansine +bevacizumab administered on day 1 of each 21-day 
cycle; alternatively, mirvetuximab soravtansine administered on day 1 and bevacizumab 
administered on days 1 and 15 of each 28-day cycle 
Regimen B: Mirvetuximab soravtansine + carboplatin administered on day 1 of each 21-day 
cycle 
Regimen C: Mirvetuximab soravtansine + pegylated liposomal doxorubicin administered on day 
1 of each 28-day cycle 
Regimen D: Mirvetuximab soravtansine + pembrolizumab administered on day 1 of each 21-day 
cycle 
Table 2: 
Planned Dose Levels (Dose Escalation) for Regimen A (Mirvetuximab 
Soravtansine + Bevacizumab) 
 
Cohort 
Regimen A 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Bevacizumabc 
(mg/kg, D1q3W) 
-1 
4 
15 
1 
5 
15 
2 
6 
15 
a Mirvetuximab soravtansine dose calculated using adjusted ideal body weight (AIBW). Maximum allowable dose 
is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of bevacizumab is 15 mg/kg. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
17 
 
 
Table 3: 
Planned Dose Levels (Dose Escalation) for Regimen B (Mirvetuximab 
Soravtansine + Carboplatin) 
 
Cohort 
Regimen B 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Carboplatinc 
(AUC, D1q3W) 
-1 
4 
AUC4 
1 
5 
AUC4 
2 
5 
AUC5 
3 
6 
AUC5 
a Mirvetuximab soravtansine dose calculated using adjusted ideal body weight (AIBW). Maximum allowable dose 
is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of carboplatin is AUC6, subject to CRC review. 
Table 4: 
Planned Dose Levels (Dose Escalation) for Regimen C (Mirvetuximab 
Soravtansine + Pegylated Liposomal Doxorubicin) 
 
Cohort 
Regimen C 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Pegylated Liposomal 
Doxorubicinc 
(mg/m2, D1q4W) 
-1 
4 
30 
1 
5 
30 
2 
5 
40 
3 
6 
40 
a Mirvetuximab soravtansine dose calculated using adjusted ideal body weight (AIBW). Maximum allowable dose 
is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c The approved dose of pegylated liposomal doxorubicin for ovarian cancer is 50 mg/m2; however, a decrease in the 
incidence of hand-foot syndrome was observed at a dose of 40 mg/m2 without a significant change in efficacy. 
Maximum allowable dose is 50 mg/m2, subject to CRC review. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
18 
 
 
Table 5: 
Planned Dose Levels (Dose Escalation) for Regimen D (Mirvetuximab 
Soravtansine + Pembrolizumab) 
 
Cohort 
Regimen D 
Mirvetuximab Soravtansinea 
(mg/kg, D1q3W)b 
Pembrolizumabc 
(mg, D1q3W) 
-1 
4 
200 
1 
5 
200 
2 
6 
200 
a Mirvetuximab soravtansine dose calculated using adjusted ideal body weight (AIBW). Maximum allowable dose 
is 6 mg/kg AIBW. 
b Day 1, every 3 weeks. 
c Maximum allowable dose of pembrolizumab is 200 mg. 
The dose escalation phase will follow a standard 3+3 cohort design. No intra-patient dose- 
escalation will be allowed. The MTD will be determined from the assessment of DLTs during 
the first treatment cycle. See Protocol Section 4.1.3.2 for further dose escalation rules, and 
Protocol Section 4.1.4 for definition of DLT. 
To better characterize safety, 10 patients may receive mirvetuximab soravtansine and the 
assigned combination agent at the MTD level established for each combination regimen. 
 
4.1.3. 
Dose Expansion Phase 
Once the CRC determines the MTD, the CRC will determine the dose and schedule to be 
administered in the dose expansion phase. The dose expansion phase will commence enrollment 
pending sponsor decision. The primary aims of the dose expansion phase are to further evaluate 
safety and tolerability and to assess preliminary anti-tumor activity of mirvetuximab soravtansine 
in combination with bevacizumab or mirvetuximab soravtansine in combination with 
pembrolizumab. Data obtained in the dose expansion phase will help define the RP2D. 
Regimen A (Mirvetuximab Soravtansine + Bevacizumab) 
Patients enrolled in the dose expansion phase may be assigned to one of two dose expansion 
cohorts according to previous exposure to bevacizumab as follows: 
1. Dose Expansion Cohort 1: bevacizumab naïve; will enroll approximately 20 patients 
2. Dose Expansion Cohort 2: bevacizumab pretreated; may enroll 35 patients 
3. Dose Expansion Cohort 3: patients with at least one but no more than three prior systemic 
treatment regimens, where prior regimens may have included bevacizumab; may enroll 
approximately 60 patients 
Regimen D (Mirvetuximab Soravtansine + Pembrolizumab) 
The dose expansion phase will enroll sufficient patients to ensure 35 patients have medium or 
high FRα expression. 
Dose expansion is planned for Regimen A and D, pending sponsor decision; however, based on 
emerging safety and preliminary anti-tumor activity data, the CRC may make the decision to 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
19 
 
 
expand Regimens B and/or C to collect additional safety information. If expanded, Regimens B 
and C will each enroll a maximum of 20 patients who will be treated at the MTD established for 
the corresponding regimen. 
Safety will be evaluated continuously, separately, and in aggregate in the expansion cohorts. If at 
any time ≥ 33% of at least 3 patients treated in an expansion cohort experiences a Cycle 1 DLT, 
further enrollment to that cohort will stop and a CRC will be convened. The CRC will review all 
available safety data to determine how further dosing should proceed. If it is decided that a new 
dose should be investigated, enrollment to the cohort will begin anew. 
 
4.1.4. 
Triplet Dose Cohort (Regimen E) 
Following evaluation of the safety, tolerability, and activity data from patients receiving 
Regimens A and B (dose escalation and dose expansion) in this study, a triplet dose cohort 
(Regimen E) will be opened. The planned doses for patients receiving the triplet dose are derived 
from all available data from Regimens A and B. Regimen E may enroll approximately 50 
patients, as exploration of alternative doses is required to enroll approximately 40 planned 
patients to be dosed at the maximum dose level determined to be safe. 
The MTD will be determined from the assessment of DLTs during the first treatment cycle. 
Initially, six patients will be dosed at the target triplet dose defined in Table 6. If there are <2 
Cycle 1 DLTs (total), a further 6 patients will be dosed. If there are <4 Cycle 1 DLTs (total) in 
all 12 patients, the remaining 28 patients will be enrolled. See Protocol Section 4.1.5 for further 
dosing rules, and Protocol Section 4.1.4 for definition of DLT. 
Table 6: 
Planned Doses Triplet Cohort Regimen E (Mirvetuximab Soravtansine + 
Bevacizumab + Carboplatin) 
 
Dose Level 
Regimen E 
Mirvetuximab 
soravtansinea 
(mg/kg, D1q3W)b 
Bevacizumab 
(mg/kg, D1q3W) 
Carboplatinc 
(AUC, D1q3W) 
-2 
5 
15 
4 
-1d 
6 
15 
4 
-1e 
5 
15 
5 
1 
6 
15 
5 
a Mirvetuximab soravtansine dose calculated using adjusted ideal body weight (AIBW). 
b Day 1, every 3 weeks. 
c Carboplatin dose may be reduced to AUC4 if safety data from the first 6 or 12 patients suggest the triplet dose is 
not being tolerated. 
d Dose reduction of Carboplatin due to Carboplatin associated toxicity. 
e Dose reduction of mirvetuximab soravtansine due to mirvetuximab soravtansine associated toxicity. 
 
4.1.5. 
Second Course Phase for Regimen D (Mirvetuximab Soravtansine + 
Pembrolizumab) 
Patients on Regimen D (mirvetuximab soravtansine + pembrolizumab) who stop mirvetuximab 
soravtansine and pembrolizumab with CR per Protocol Section 5.10.6.4.1 may be eligible for up 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
20 
 
 
to 1 year of additional treatment with pembrolizumab in combination with mirvetuximab 
soravtansine or as monotherapy if they progress after stopping study treatment. This Second 
Course Phase of this study is available only if the study remains open and the patient meets the 
following conditions: 
• Stopped initial treatment with mirvetuximab soravtansine and pembrolizumab after 
attaining an investigator-determined confirmed CR according to RECIST Version 
1.1. 
− Was treated for at least 24 weeks with mirvetuximab soravtansine and 
pembrolizumab before discontinuing therapy. 
− Received at least two treatments with mirvetuximab soravtansine and 
pembrolizumab beyond the date when the initial CR was declared. 
AND 
• Experienced Investigator-determined confirmed radiologic PD after stopping their 
initial treatment with mirvetuximab soravtansine and pembrolizumab. 
• Did not receive any anti-cancer treatment since the last dose of mirvetuximab 
soravtansine and pembrolizumab. 
• Has a performance status of 0 or 1 on the ECOG PS. 
• Demonstrates adequate organ function as detailed in the inclusion criteria 
(Protocol Section 3.1). 
• If WCBP, defined as a sexually mature woman who has not undergone surgical 
sterilization or who has not been naturally postmenopausal for at least 12 consecutive 
months (ie, who has had menses any time in the preceding 12 consecutive months): 
has a negative serum or urine pregnancy test within 72 hours before receiving 
retreatment with study medication. 
• If WCBP: agrees to use effective contraceptive methods (examples include oral, 
parenteral, or implantable hormonal contraceptive, intra-uterine device, or 
vasectomy) while on study treatment and for at least 12 weeks after the last dose of 
mirvetuximab soravtansine and for at least 4 months after the last dose of 
pembrolizumab. 
• Does not have a history or current evidence of any condition, therapy, or laboratory 
abnormality that a) might interfere with the patient’s participation for the full duration 
of the study, or b) makes it not in the best interest of the patient to participate, in the 
opinion of the treating Investigator. 
Patients who restart treatment will be retreated at the same dose frequency as when they last 
received pembrolizumab and mirvetuximab soravtansine. Treatment will be administered for up 
to 1 additional year. Patients will follow the Schedule of Clinical Assessments in 
Protocol Appendix C. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
21 
 
 
4.2. 
Study Period Schema 
Figure 2 below illustrates the Study Periods for each Regimen. The periods are defined by 
regimen and will be the same for the Dose Escalation and Dose Expansion phases of the trial. 
Figure 2: 
Study Period Schema 
 
1 Discontinuation of treatment may be considered for patients who have attained a confirmed complete response 
(CR) that have been treated for at least 24 weeks with mirvetuximab soravtansine+pembrolizumab and had at least 
2 cycles with mirvetuximab soravtansine+pembrolizumab beyond the date when the initial CR was declared. 
Retreatment with pembrolizumab in combination with mirvetuximab soravtansine or as monotherapy may be 
considered if the patient has a CR and meets the criteria in the protocol. 
2 This is the period of time between the discontinuation of pembrolizumab or mirvetuximab 
soravtansine+pembrolizumab, and the start of the second course phase treatment. 
3 Second Course Phase Treatment has separate baselines for efficacy and safety analyses. For safety analyses, the 
baseline is the same as the baseline for the Primary Treatment period (i.e. the last non-missing value on or prior to 
the first dose of study treatment). For efficacy analyses, the baseline is the last non-missing value on or prior to 
the first SCP treatment. 
 
4.3. 
Study Population 
See Protocol Section 3.1 for a complete list of the inclusion/exclusion criteria. 
 
4.3.1. 
Enrolled Patient and Screen Failure Definitions 
Patients who have signed an IRB/IEC approved informed consent form the study and who have 
received at least one dose of study treatment will be considered enrolled. Patients who are issued 
a patient number, but who do not successfully complete the screening process and who do not 
receive a dose of mirvetuximab soravtansine and/or combination drug will be considered a 
screen failure. Patient numbers for patients who screen fail will not be re-issued. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
22 
 
 
4.4. 
Sample Size Predictions 
4.4.1. 
Dose Escalation 
Ascending doses of mirvetuximab soravtansine and bevacizumab, carboplatin, pegylated 
liposomal doxorubicin or pembrolizumab are to be evaluated to identify the MTD for each of the 
four combination regimens. The actual number of patients accrued during the dose escalation 
phase will be determined largely by the findings observed during the course of their treatment. 
Regimen A (mirvetuximab soravtansine + bevacizumab) is expected to enroll 16 patients 
whereas Regimens B (mirvetuximab soravtansine + carboplatin) and C (mirvetuximab 
soravtansine + pegylated liposomal doxorubicin) are expected to enroll 22 patients. Regimen D 
(mirvetuximab soravtansine + pembrolizumab) is expected to enroll 16 patients. 
For all four regimens, 10 patients may be treated at the MTD. 
Overall, the dose escalation phase of the study is expected to enroll approximately 76-120 
patients. 
4.4.2. 
Dose Expansion 
Following MTD determination, there will be an expansion phase for Regimen A (mirvetuximab 
soravtansine + bevacizumab) and Regimen D (mirvetuximab soravtansine + pembrolizumab). 
Overall, the dose expansion phase is expected to enroll up to 130 patients. 
Regimen A (Mirvetuximab Soravtansine + Bevacizumab) 
Patients enrolled in the dose expansion phase will be allocated to three Dose Expansion Cohorts 
according to prior exposure to bevacizumab and disease diagnosis as follows: 1) Dose expansion 
Cohort 1: bevacizumabnaïve; 2) Dose expansion Cohort 2: bevacizumab pretreated; and 3) Dose 
expansion cohort 3: patients with at least one but no more than three prior systemic treatment 
regimens, where prior regimens may have included bevacizumab. 
For the bevacizumab naïve cohort (Cohort 1), assuming a response rate of 55%, there is a 94.2% 
probability of detecting at least 8 responders if 20 patients are recruited. The response rate 
assumption is based on an ORR of 53% observed with the standard of care therapy of paclitaxel 
in combination with bevacizumab in patients with platinum-resistant EOC (Bevacizumab 
[package insert] 2014). 
For the bevacizumab pretreated cohort (Cohort 2), assuming a response rate of 50%, there is a 
91.2% probability of detecting at least 14 responders if 35 patients are recruited. 
For the bevacizumab expansion cohort 3, assuming a response rate of 50%, there is a 95.4% 
probability of detecting at least 24 response if 60 patients are recruited. In addition, the 90% 
confidence interval for true ORR is given in Table 7 below if the observed number of responders 
is between 20 and 40 of 60 patients. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
Table 7: 
Confidence Interval (90%) for True ORR with Sample Size = 60 
23 
 
 
 
Responses Observed, 60 patients 
90% Exact Confidence Interval for True ORR 
20/60 (33%) 
(23%, 45%) 
21/60 (35%) 
(25%, 46%) 
22/60 (37%) 
(26%, 48%) 
23/60 (38%) 
(28%, 50%) 
24/60 (40%) 
(29%, 51%) 
25/60 (42%) 
(31%, 53%) 
26/60 (43%) 
(32%, 55%) 
27/60 (45%) 
(34%, 56%) 
28/60 (47%) 
(36%, 58%) 
29/60 (48%) 
(37%, 60%) 
30/60 (50%) 
(39%, 61%) 
31/60 (52%) 
(40%, 63%) 
32/60 (53%) 
(42%, 64%) 
33/60 (55%) 
(44%, 66%) 
34/60 (57%) 
(45%, 68%) 
35/60 (58%) 
(47%, 69%) 
36/60 (60%) 
(49%, 71%) 
37/60 (62%) 
(50%, 72%) 
38/60 (63%) 
(52%, 74%) 
39/60 (65%) 
(54%, 75%) 
40/60 (67%) 
(55%, 77%) 
Regimen D (Mirvetuximab Soravtansine+ Pembrolizumab): 
In the dose expansion phase for Regimen D, a total of 35 patients will be enrolled with medium 
or high FRα expression and 11 patients with a low FRα expression. Assuming a response rate of 
50%, there is a 91.2% probability of detecting at least 14 responders if 35 patients are recruited. 
In addition, the 90% confidence interval for true ORR is given in Table 8 below if the observed 
number of responders is 12-18 out of 35 patients. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
24 
 
 
Table 8: 
Confidence Interval (90%) for True ORR with Sample Size = 35 
 
Responses observed out of 35 patients 
90% exact confidence interval for true ORR rate 
12/35 (34%) 
(21%, 50%) 
13/35 (37%) 
(24%, 52%) 
14/35 (40%) 
(26%, 55%) 
15/35 (43%) 
(29%, 58%) 
16/35 (46%) 
(31%, 61%) 
17/35 (49%) 
(34%, 64%) 
18/35 (51%) 
(36%, 66%) 
Regimen E (Mirvetuximab Soravtansine + Bevacizumab + Carboplatin): 
In Regimen E (triplet), approximately 50 patients will be enrolled to ensure 40 patients will be 
treated at the MTD. Assuming a response rate of 60%, there is a 92.6% probability of detecting 
at least 20 responders if 40 patients are recruited. In addition, the 90% confidence interval for 
true ORR is given in Table 9 if the observed number of responders is 20-26 out of 40 patients. 
Table 9: 
Confidence Interval (90%) for True ORR with Sample Size = 40 
 
Responses observed out of 40 patients 
90% exact confidence interval for true ORR rate 
20/40 (50.0%) 
(36%, 64%) 
21/40 (52.5%) 
(38%, 66%) 
22/40 (55.0%) 
(41%, 69%) 
23/40 (57.5%) 
(43%, 71%) 
24/40 (60.0%) 
(46%, 73%) 
25/40 (62.5%) 
(48%, 75%) 
26/40 (65.0%) 
(51%, 77%) 
 
4.4.3. 
Overall 
Overall, the dose escalation phase of the study is expected to enroll approximately 76-120 
patients and the dose expansion phase is expected to enroll up to 211 patients. Assuming that 
approximately 90% of enrolled patients will be evaluable, the trial is projected to accrue 
approximately 311-355 patients. 
 
4.5. 
Treatment Randomization 
No randomization will be performed in this study. 
 
4.6. 
Assessment Schedule 
See Protocol Appendices A-D for the study schedule of assessments. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
25 
 
 
5. 
INTERVENTIONS 
5.1. 
Clinical Trial Material 
For all regimens, the total dose of mirvetuximab soravtansine will be calculated according to 
AIBW. Mirvetuximab soravtansine should be administered first, followed by the assigned 
combination drug (bevacizumab, carboplatin, pegylated liposomal doxorubicin or 
pembrolizumab). 
For Regimen A (Mirvetuximab Soravtansine + Bevacizumab): 
Mirvetuximab soravtansine and bevacizumab will be administered on day 1 of each 21-day 
cycle. 
For Regimen B (Mirvetuximab Soravtansine + Carboplatin): 
Mirvetuximab soravtansine and carboplatin will be administered on day 1 of each 21-day cycle. 
For Regimen C (Mirvetuximab Soravtansine + Pegylated Liposomal Doxorubicin): 
Mirvetuximab soravtansine and pegylated liposomal doxorubicin will be administered on day 1 
of each 28-day cycle. 
For Regimen D (Mirvetuximab Soravtansine + Pembrolizumab): 
Mirvetuximab soravtansine and pembrolizumab will be administered on day 1 of each 21-day 
cycle. 
For Regimen E (Mirvetuximab Soravtansine + Bevacizumab + Carboplatin): 
Mirvetuximab soravtansine, followed by bevacizumab and then carboplatin will be administered 
on day 1 of each 21-day cycle. 
Protocol Section 5 provides additional details. 
 
6. 
GENERAL ANALYTICAL CONSIDERATIONS 
6.1. 
Data Sources 
Data are recorded on electronic case report forms (eCRFs). Central laboratory data will be 
provided via electronic data transfers. Protocol Section 12 provides additional details regarding 
data recording and handling. 
 
6.2. 
Definition of Baseline 
Study Day 1 will be designated as the first day a patient receives study drug (i.e. Cycle 1 Day 1). 
The baseline value for the Primary Treatment period is defined as the last non-missing value on 
or prior to the first dose of study treatment. Patients in Regimen D who experience a CR may 
withdraw from treatment and enter the optional Pre-Second Course Phase period. The baseline 
for the Pre-Second Course Phase period will be the same as the baseline for the Primary 
Treatment period (i.e. the last non-missing value on or prior to the first dose of study treatment). 
For patients in Regimen D who enter the optional Second Course Phase Treatment period, the 
baseline for the Second Course Phase for efficacy analyses will be the last non-missing 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
26 
 
 
assessment following the last mirvetuximab soravtansine+pembrolizumab treatment in the 
Primary Treatment period, and on or prior to the first mirvetuximab 
soravtansine+pembrolizumab or pembrolizumab treatment in the Second Course Phase treatment 
period. The baseline for the Second Course Phase for safety analyses will be the last non- 
missing value on or prior to the first dose of study treatment (note: this is the same as the 
baseline definition for the primary treatment period). For ECG assessments, this may be the 
average of replicate readings. 
 
6.3. 
Missing Data 
Partial dates are allowed on the CRF for Adverse Event (AE) onset and resolution dates, 
Concomitant Medication (CM) start and stop dates, and Concomitant Procedure (CP) procedure 
dates. An entry for the year is required in the eCRF system for each of these dates. Only the 
month and day may be entered as unknown. Dates from these forms will be reported in listings 
as collected. Every effort will be made to query missing dates. 
For records with a missing AE onset date, the following procedure will be employed for use in 
determining whether the AE is treatment-emergent: 
• AE onset dates with missing day and non-missing month will be assumed to occur on 
the first day of the non-missing month, except for AEs occurring in the first month of 
dosing, in which case the date will be the first day of dosing. 
• AE onset dates with missing month will be assumed to occur on the first day of the 
non-missing year (i.e. January 1), except for AEs occurring in the first year of dosing, 
in which case the date will be the first day of dosing. 
For records with a missing medication start and/or stop date, the following procedure will be 
employed for use in determining whether the medication is prior or concomitant: 
• Medication start dates with a missing day and non-missing month will be assumed to 
occur on the first day of the non-missing month, except for medications occurring in 
the first month of dosing, in which case the date will be the first day of dosing. 
• Medication start dates with missing month will be assumed to occur on the first day 
of the non-missing year (i.e. January 1), except for medications occurring in the first 
year of dosing, in which case the date will be the first day of dosing. 
• Medications that are not ongoing, and have a medication stop date with a missing day 
and non-missing month will be assumed to occur on the last day of the non-missing 
month. 
• Medications that are not ongoing, and have a medication stop date with a missing 
month will be assumed to occur on the last day of the non-missing year (i.e. 
December 31). 
For records with a missing procedure date, the following procedure will be employed for use in 
determining whether the procedure is prior or concomitant: 
• Procedure dates with a missing day and non-missing month will be assumed to occur 
on the first day of the non-missing month, except for procedures occurring in the first 
month of dosing, in which case the date will be the first day of dosing. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
27 
 
 
• Procedure dates with missing month will be assumed to occur on the first day of the 
non-missing year (i.e. January 1), except for procedures occurring in the first year of 
dosing, in which case the date will be the first day of dosing. 
All other data will be reported as they are collected. No imputation methods will be used to 
replace missing data unless otherwise stated in this document. 
 
6.4. 
Multiple Assessments for the Same Assessment Time Point 
In the case of multiple observations at a specific visit, the first non-missing measurement will be 
used for analysis, unless multiple study assessments are expected (e.g. pre-dose vs. post-dose). 
When multiple study assessments are expected, the first non-missing measurement for the visit 
and assessment time point will be used for analysis. The exception to this rule will be for 
triplicate ECGs, for which the average of the three triplicates will be used for analysis. 
 
6.5. 
Multiple Study Centers 
No adjustment for study center is planned. 
 
6.6. 
Covariate Adjustment in Primary Analysis 
No covariate adjustments are planned. 
 
6.7. 
Sample Size Reassessment 
Not applicable. 
 
6.8. 
Interim Analyses or Timing of Analyses 
No formal interim analysis is planned for this study. However, a review of safety data will be 
conducted by the CRC upon completion of each dose escalation cohort, and at least every 4 
weeks during MTD Dose Expansion. Results from this data review could enable selection of 
dose for additional studies with mirvetuximab soravtansine, before full completion of this study. 
 
6.9. 
Test Sizes 
No formal statistical hypothesis tests are planned. 95% confidence intervals will be provided 
where specified. Any tested hypotheses will be tested against two-sided alternatives, using 
procedures that provide an expected probability of Type I error (α) of 0.05. 
 
6.10. 
Multiple Comparisons 
No control for the effect of multiple comparisons is planned. 
 
6.11. 
Analysis Populations 
Four analysis populations will be defined for use with various analyses. The following table 
illustrates the relationship between each population and the analyses for which the data from the 
population will be used. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
28 
 
 
 
Analysis Population 
Analysis 
Baseline 
Patient Disposition 
Efficacy 
Safety 
Safety 
X 
X 
X 
Response- Evaluable 
X 
CA125 Evaluable 
X 
 
6.11.1 Screened 
The Screened population includes all patients entered into the eCRF system who have signed an 
informed consent. 
 
6.11.2 Safety Population 
All patients who received at least one dose of study treatment (mirvetuximab soravtansine, 
bevacizumab, carboplatin, pegylated liposomal doxorubicin or pembrolizumab) will be included 
in the Safety population. 
 
6.11.3 Response-Evaluable Population 
To meet the definition of response-evaluable, patients must have undergone radiographic 
assessment at baseline, received at least one dose of combination treatment (i.e. mirvetuximab 
soravtansine with bevacizumab, carboplatin, pegylated liposomal doxorubicin or 
pembrolizumab), and must have had at least one post-dose radiographic tumor assessment or 
have died with 105 days of first dose. 
 
6.11.4 CA125 Evaluable Population 
The CA125 evaluable population is defined as all patients whose pretreatment sample is ≥ 2.0 
times the ULN, within 2 weeks prior to the first dose of combination treatment, and who have at 
least one post-baseline CA125 evaluation. 
6.12. 
Data Display Characteristics 
Data displays produced for this study will include three types—summary tables, data listings, 
and figures. Unless stated otherwise, data listings will be produced for all recorded data. 
Summary tables will be produced as specified in the following sections. Additional data listings 
will be produced for outcome measures that involve extensive procedures to derive the analyzed 
outcomes. Figures will be produced when specified in sections to follow. 
Unless otherwise specified, tables and figures will be presented separately for the Dose 
Escalation and Dose Expansion phases of the study. Data listings will display data from both 
phases of the study. 
Data listings will simply list the data recorded on the eCRF or derived for each patient. They 
will be ordered by study phase (Dose Escalation followed by Dose Expansion), treatment, site, 
patient number, and date/time of assessment. When expedient, additional levels of ordering 
hierarchy may reflect subsets of assessments within patient. Data listings will not display patient 
initials. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
29 
 
 
Summary tables will display summary statistics calculated for each regimen and cohort. Separate 
tables will be generated for each regimen, and the presentation of cohorts will depend on the type 
of analysis, as described in the following sections. 
Summaries of demographics, disposition, and baseline characteristics will be presented by 
escalation cohort for Regimens B and C, and will include a total column summarizing all 
escalation cohorts. For Regimens A and D, summaries will be presented by escalation and 
expansion cohort, and will include a total column summarizing all escalation and expansion 
patients who receive a full dose of mirvetuximab soravtansine. All patients enrolled in Regimen 
E will be summarized in one column. Each regimen will be presented on a separate page. 
Summaries of safety data will be presented by dose cohort for Regimens B and C and will not 
include a total column. For Regimens A and D, summaries will be presented by dose cohort, 
combining patients who receive a full dose of mirvetuximab soravtansine. All patients enrolled 
in Regimen E will be summarized in one column. Each regimen will be presented on a separate 
page. 
Summaries of efficacy data will be presented for all dosed patients by escalation cohort for 
Regimens B and C and by escalation and expansion cohort for Regimens A and D. A total 
column will be included. For Regimen E, efficacy endpoints will be summarized in one column. 
The summary statistics displayed will be a function of the type of data associated with the 
summarized assessment. Unless stated otherwise in relevant sections to follow, continuous data 
will be summarized with the number of non-missing values, mean, standard deviation, minimum, 
median, and maximum. Categorical data will be summarized with the number of non-missing 
values and the numbers of values equal to each of the possible values. Percentages of patients 
with each of the possible values will be calculated from the number of patients in the 
corresponding analysis population, unless stated otherwise. Some continuous variables may also 
be grouped into categorical levels and evaluated in frequency tables. 
 
7. 
PATIENT ACCOUNTABILITY 
7.1. 
Patient Characteristics 
Patient characteristics will be summarized for the Safety population using the treatment actually 
received (i.e. the actual treatment arm variable(s) in SDTM/ADaM). 
Demography. Data collected about the following patient characteristics at the screening visit 
will be summarized: 
• Age. Age is collected in the eCRF system. As this is a global study, there are certain 
regions where local regulations prohibit the collection of a complete date of birth. 
Therefore, age will not be recalculated for analysis purposes. The collected age will 
be used for summarization. 
• Sex and childbearing potential yes/no 
• Ethnicity 
• Race 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
30 
 
 
All demography data including informed consent date will be listed. 
Height, Baseline Weight, Baseline AIBW and Baseline BSA. Height, baseline weight, baseline 
AIBW and baseline body surface area (BSA) will be summarized by treatment group and 
presented in a listing. Note that BSA is collected depending on the treatment group (i.e. 
combination agent) to which a patient is assigned. Thus, baseline BSA will only be summarized 
for the treatment groups for which these data are available. 
Medical History. Medical history will be coded using MedDRA (version 21.0 or later), 
associating lower-level terms with preferred terms and system organ classes by the primary 
hierarchy. Medical Histories will be summarized as the numbers and percentages of patients 
who reported at least one medical history event, numbers and percentages of patients who 
reported at least one medical history event in each system organ class. Within each system organ 
class, the tables will display the counts and percentages of patients reporting at least one medical 
history event as designated by the preferred terms. All medical history information will also be 
listed. 
Disease Characteristics, Prior Therapy, and Gene Mutations. Listings of all collected data 
related to disease characteristics and prior therapy will be provided. A summary of the following 
elements will also be provided: 
• Primary diagnosis (epithelial ovarian, fallopian tube, primary peritoneal, other) 
• Folate receptor alpha status 
− low 
− medium 
− high 
• BRCA mutation status 
• Histology 
• Stage at initial diagnosis 
• Histologic grade 
• Prior radiotherapy (yes/no) 
• Prior systemic therapy (yes/no, number of prior therapies) 
− The number of prior systemic therapies is defined as the number of distinct 
regimens. 
 Adjuvant±Neoadjuvant will be considered as one regimen 
 Maintenance therapy will be considered to be part of the preceding regimen 
 PARP inhibitor therapy will be considered as a prior treatment 
• Prior surgery (yes/no) 
• Baseline ECOG performance status 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
31 
 
 
• Platinum free interval, definded as time from last dose of prior platinum therapy to 
disease progression or relapse following last line of prior platinum therapy (<=6 
months, > 6 months) (Regimen A only) 
 
7.2. 
Patient Disposition 
7.2.1 Screened Patients 
For patients who failed screening, the number and percentage of patients will be summarized in a 
table by the reasons for screen failure. The reasons for screen failure will also be provided in a 
listing. 
7.2.2 Safety Population 
Disposition will be summarized for the Safety population using the treatment actually received 
(i.e. the actual treatment arm variable(s) in SDTM/ADaM). 
Safety Disposition. A summary of patient disposition will summarize, for the Safety population, 
the numbers of patients who received study treatment and the reasons for treatment and study 
discontinuation. For Regimen D, the number of patients who continued into the Pre-Second 
Course Phase and Second Course Phase of treatment and the reasons for Second Course 
treatment discontinuation will be provided. 
Percentages of patients who withdrew for each of the reasons on the End of Treatment and End 
of Study forms will be calculated using all members of the Safety population in the relevant 
treatment group for the denominator. For Regimen D, Second Course Phase of treatment 
summary, percentages of patients who withdrew for each of the reasons on the Second Course 
End of Treatment form will be calculated using the number of patients who entered the Second 
Course Phase of treatment as the denominator. 
A listing of the End of Treatment and End of Study information will be provided for the Safety 
population. 
Deaths. A summary table and listing of all reported deaths will be provided. 
 
7.3. 
Protocol Deviations and Population Inclusions 
Protocol deviations will be summarized for the Safety population using the treatment actually 
received (i.e. the actual treatment arm variable(s) in SDTM/ADaM). 
Protocol deviations will be captured in a protocol deviation log. A summary of the number of 
patients with any protocol deviation by treatment group will be provided. 
Protocol deviations will also be summarized by the following categories: 
• Those who entered the study even though they did not satisfy the entry criteria 
• Those who developed withdrawal criteria during the study but were not withdrawn 
• Those who received the wrong treatment or incorrect dose 
• Those who received an excluded concomitant treatment 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
32 
 
 
The summary will be grouped first by deviation categories and then by site within each deviation 
category. 
A listing from the protocol deviation log will be provided for patients who were enrolled even 
though they did not meet one or more eligibility criteria and patients who met withdrawal criteria 
discernible from recorded data during the study but were not withdrawn. 
A hierarchical table of the populations in which Screened patients were included will summarize 
the relationship of the analysis populations. The number of screened patients will be provided in 
the Total column. Given population definitions, the Safety population will be treated as the 
starting, parent population. The numbers and percentages of Safety patients included in the 
Response-Evaluable population, and the CA125 Evaluable population will be presented for each 
treatment group. 
 
8. 
EFFICACY ANALYSES 
All efficacy analyses for RECIST-related variables will use data from the Response-Evaluable 
population. CA125 response analyses will use the CA125 Evaluable population. Patients will be 
analyzed by the treatment they actually received (i.e. the actual treatment arm variable(s) in 
SDTM/ADaM). 
 
8.1. 
Efficacy Outcomes 
CA125 Response. A CA125 response is defined as a ≥ 50% reduction in CA125 levels from 
baseline. The response must be confirmed and maintained for at least 28 days. The CA125 
response will be analyzed using the CA125 Evaluable population. The date of response 
corresponds to the date when the CA125 level is first reduced by 50% or more. The summary 
table for CA125 will include a summarization of the n (%) of patients in the CA125 Evaluable 
population, and that n will then be used as the denominator for CA125 response rate. 
RECIST and Immune-Related RECIST (irRECIST) Related Endpoints. Tumor response will be 
measured by RECIST v1.1 for Regimens A, B, C, D, and E. Immune-related RECIST 
(irRECIST) will be used to evaluate tumor response for Regimen D. All endpoints described 
below will use RECIST or irRECIST based on the regimen. PFS, ORR and DOR per irRECIST 
are defined as specified for the respective endpoints using RECIST 1.1 below, with the exception 
that a confirmation assessment of PD (at least 4 weeks after the initial PD assessment) is required 
for patients who remain on treatment following a documented PD per RECIST 1.1. Patients who 
discontinue treatment following a documented PD assessment per RECIST 1.1 will be counted 
as having disease progression on the date of the documented PD assessment.  See 
Protocol Appendix I for further details. 
Best Overall Response (BOR). Best overall response for a patient is the best response 
designation as assessed by the investigator, recorded between the date of the first dose of study 
treatment and the date of objectively documented progression per RECIST v1.1 or the date of 
treatment discontinuation, whichever occurs first. Patients with an overall response of CR or PR 
must have a repeat tumor assessment performed no less than 4 weeks (28 days) after the criteria 
for response are first met. Patients with an overall response of SD must have a minimum 
duration of 35 days (6 weeks – 1 week window = 35 days; with 6 weeks being the most frequent 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
33 
 
 
scheduled radiographic tumor assessment for the study). The confirmatory scan is valid 
following treatment discontinuation as long as the patient has not started a new anti-cancer 
therapy. 
Objective Response Rate (ORR). The ORR will be calculated as the number of patients with a 
BOR of CR or PR divided by the number of patients in the analysis population. Patients without 
at least one post-baseline RECIST assessment will be treated as non-responders. That is, these 
patients will contribute to the denominator, but not the numerator. Response or progression in 
the Second Course Phase for Regimen D patients will not count towards the ORR of the primary 
endpoint in this trial. 
Progression Free Survival (PFS). PFS is defined as the time from the date of the first dose of 
study drug until the date of progressive disease (PD) or death from any cause, whichever occurs 
first. PFS is defined based on radiological assessments and determined by the investigator. 
Clinical progression is not considered a progression endpoint. 
Table 10 provides a summary of the rules to be used for PFS. When an analysis cutoff date is 
implemented, only data (deaths and radiological assessments) occurring on or prior to the cutoff 
date will be used for analysis. 
Table 10: 
PFS Definitions (includes investigator assessed radiographic progression 
only) 
 
Situation 
Date of PFS Event or Censoring 
Outcome 
No baseline tumor assessments or post- 
baseline radiological assessments and patient 
did not die within 105 days of Day 1 
Date of first dose of study drug 
Censored 
No baseline tumor assessments or post- 
baseline radiological assessments and patient 
died within 105 days of Day 1 
Date of death 
Death 
Death 
Date of death 
Death 
Radiological Progression 
Date of first radiological assessment 
indicating progression (i.e Overall 
Response = Progressive Disease on 
RECIST Response CRF). 
Progression 
New anti-cancer therapy prior to PD or death 
(including palliative radiotherapy during study 
treatment) 
Date of last radiological assessment 
prior to the start of the new anticancer 
therapy 
Censored 
No death or progression 
Date of last radiological assessment 
Censored 
PD or death after missing two or more 
consecutive radiological assessments (PD or 
death date – last radiological assessment date 
+1 >=105 days) 
Date of last adequate radiological 
assessment showing no PD 
Censored 
Duration of Response (DOR). DOR is defined as the time from the date of the first response (CR 
or PR), whichever is recorded first, to the date of progressive disease (PD) or death from any 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
34 
 
 
cause, whichever occurs first. Duration of response is only defined for patients who have a best 
overall response of CR or PR. 
Per the BOR definition, patients with an overall response of CR or PR must have a repeat tumor 
assessment performed no less than 4 weeks after the criteria for response are first met. The first 
date at which a CR or PR response was noted will be used to calculate DOR, not the date of the 
confirmatory tumor assessment. 
Patients who started a new anti-cancer therapy prior to documented PD or death will be censored 
at the last radiological assessment prior to initiation of new anti-cancer therapy. Patients who did 
not have PD or death will be censored at the date of their last radiological assessment. Patients 
who had PD or death after missing two or more consecutive radiological assessments (PD or 
death date – last radiological assessment date +1 >=105 days) will be censored at the date of 
their last radiological assessment. When an analysis cutoff date is implemented, only data 
(deaths or radiological assessments) occurring on or prior to the cutoff date will be used for 
analysis. 
Overall Survival (OS). OS is defined as the time from the date of the first dose of study 
treatment until the date of death from any cause. 
Patients who are alive or lost to follow-up at the analysis are censored at the last known date at 
which they were known to be alive. When an analysis cutoff date is implemented, only deaths 
occurring on or prior to the cutoff date are counted as OS events. Patients whose date of death or 
last date at which the patient was known to be alive is after the data cutoff date will be censored 
at the analysis cutoff date. 
Table 11 provides a summary of the efficacy analyses planned for the study. These analyses are 
further described in Section 8.2, Section 8.3, and Section 8.4 below. 
Table 11: 
Summary of Efficacy Analysis 
 
Efficacy Analysis 
Regimen 
A 
B 
C 
D 
E 
Esc 
Exp 
Esc 
Esc 
Esc 
Exp 
Primary 
Number of Patients with RECIST 
1.1 Clinical Responses 
Objective Response Rate 
X 
X 
X 
Secondary 
Number of Patients with RECIST 
1.1 Clinical Responses 
Objective Response Rate 
X 
X 
X 
X 
RECIST 1.1 Progression-Free 
Survival 
X 
X 
X 
X 
X 
X 
X 
RECIST 1.1 Duration of Response 
X 
X 
X 
X 
X 
X 
X 
Number of Patients with 
Gynecologic Cancer Intergroup 
(GCIG) CA125 Criteria Clinical 
Responses 
X 
X 
X 
X 
X 
X 
X 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
35 
 
 
 
Efficacy Analysis 
Regimen 
A 
B 
C 
D 
E 
Esc 
Exp 
Esc 
Esc 
Esc 
Exp 
CA125 Response Rate 
Overall Survival 
X 
X 
X 
X 
X 
X 
X 
Exploratory 
Number of Patients with irRECIST 
Clinical Response 
Objective Response Rate 
Progression Free Survival 
Duration of Response 
X 
X 
 
8.2. 
Primary Efficacy Outcome Analysis 
There is no primary efficacy endpoint for the Dose Escalation phase of the study. 
The protocol specifies the following primary efficacy endpoints for the Dose Expansion phase of 
the study: 
Regimen A and Regimen D (Dose Expansion cohorts) and Regimen E 
• Number of patients with RECIST 1.1 criteria clinical responses 
• RECIST 1.1 objective response rate (ORR) 
• Note: Response or progression in the Second Course Phase for Regimen D patients 
will not count towards the ORR of the primary endpoint in this trial. 
 
8.3. 
Secondary Efficacy Analyses 
The protocol describes the following secondary efficacy endpoints: 
Regimens A through D (Dose Escalation cohorts) 
• Number of patients with RECIST 1.1 criteria clinical responses 
• RECIST 1.1 objective response rate (ORR) 
Regimens A through D (Dose Escalation and Dose Expansion cohorts) and Regimen E 
• RECIST 1.1 progression-free survival (PFS) 
• RECIST 1.1 duration of response (DOR) 
• Number of patients with GCIG CA125 criteria clinical responses 
• GCIG CA125 Response Rate 
• Overall Survival (OS) 
The distribution of time-to-event variables (PFS, DOR, and OS) will be summarized using the 
Kaplan-Meier method. Median times will be estimated for each treatment group from the 50th 
percentile of the corresponding Kaplan-Meier estimates. The 6 month rates will be estimated for 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
36 
 
 
each treatment group from the corresponding Kaplan-Meier estimates at the 6 month time point. 
The 95% confidence intervals will also be provided. 
 
8.4. 
Exploratory Efficacy Analyses 
The protocol describes the following exploratory efficacy endpoints for Regimen D only: 
Regimen D (Dose Escalation and Dose Expansion cohorts) 
• Number of patients with irRECIST 1.1 criteria clinical responses 
• irRECIST 1.1 objective response rate (ORR) 
• irRECIST 1.1 duration of response (DOR) 
• irRECIST 1.1 progression-free survival (PFS) 
The distribution of time-to-event variables (PFS, DOR) will be summarized using the Kaplan- 
Meier method. Median time will be estimated for each treatment group from the 50th percentile 
of the corresponding Kaplan-Meier estimates. The 6 month rate will be estimated for each 
treatment group from the corresponding Kaplan-Meier estimates at the 6 month time point. The 
95% confidence interval will also be provided. 
 
8.5. 
Efficacy Analysis on Subgroups of Patients 
Efficacy analysis on the following subgroups of patients will be conducted for Regimens A, D 
and E for patients receiving full dosing of mirvetuximab soravtansine (6 mg/kg) in either 
escalation or expansion cohorts. 
• Folate receptor alpha status (FRα) 
− Low (Regimens A and D only) 
− medium 
− high 
• Number of prior lines of therapy 
− 1 
− 2-3 
− ≥4 (Regimens A and D only) 
• Platinum free interval (Regimen A only) 
− ≤ 6 months 
− > 6 months 
• Prior exposure to bevacizumab (Regimen A only) 
− Yes 
− No 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
37 
 
 
8.6. 
Sensitivity Analyses 
No formal sensitivity analyses are planned. 
 
8.7. 
Other Efficacy-related Summaries 
Listings of efficacy-related data will include: 
• All lesion assessments (target lesion, non-target lesion, new lesion) 
• Investigator’s RECIST assessments 
• CA125 results 
• Derived parameters for CA125 response, BOR, PFS, DOR, and OS 
• Censoring for time-to-event variables 
 
9. 
SAFETY ANALYSES 
Safety analyses will use data from the Safety population. Patients will be analyzed according to 
the actual study treatment received (i.e. the actual treatment arm variable(s) in SDTM/ADaM). 
 
9.1. 
Exposure 
Exposure to mirvetuximab soravtansine, bevacizumab, carboplatin, pegylated liposomal 
doxorubicin, and pembrolizumab will be summarized with descriptive statistics for the number 
of doses received, the number of cycles received, duration of dosing (weeks), total cumulative 
dose (AUC for carboplatin, mg for remaining investigational products), and total volume infused 
(mL). Absolute dose intensity and relative dose intensity will also be calculated and summarized 
for each investigational product, as shown in the following table. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
38 
 
 
 
Investigational Product 
Absolute Dose Intensity1 
Relative Dose 
Intensity 
Mirvetuximab 
Soravtansine 
Units 
mg/kg/dose 
% 
Calculation 
Total Cumulative Dose (mg)/ 
Expected Number of 
Doses/AIBW (kg) 
[Absolute Dose 
Intensity/6] x 100% 
Bevacizumab 
Units 
mg/kg/dose 
% 
Calculation 
Total Cumulative Dose (mg)/ 
Expected Number of Doses/ 
Body Weight at C1D1 (kg) 
[Absolute Dose 
Intensity/15] x 
100% 
Carboplatin 
Units 
mg/m2/week 
N/A 
Calculation 
Total Cumulative Dose (mg)/ 
BSA (m2) / Duration of dosing 
(weeks) 
N/A 
Pegylated Liposomal 
Doxorubicin 
Units 
mg/m2/dose 
% 
Calculation 
Total Cumulative Dose (mg)/ 
Expected Number of 
Doses/BSA (m2) 
[Absolute Dose 
Intensity/40] x 
100% 
Pembrolizumab 
Units 
mg/dose 
% 
Calculation 
Total Cumulative Dose (mg)/ 
Expected Number of Doses 
[Absolute Dose 
Intensity/200] x 
100% 
1 For investigational products administered Q3W (mirvetuximab soravtansine, bevacizumab, carboplatin, 
pembrolizumab), the expected number of doses is defined as the duration of dosing in weeks / 3, where duration of 
dosing is defined as (date of last dose – date of first dose + 21) / 7. For investigational products administered Q4W 
(pegylated liposomal doxorubicin), the expected number of doses is defined as the duration of dosing in weeks / 4, 
where duration of dosing is defined as (date of last dose – date of first dose + 28) / 7. 
The number of infusions with dose decreased, infusions interrupted, and dose delayed will also 
be summarized by regimen and study drug. The number of infusions with the rate of infusion 
decreased will also be summarized for the mirvetuximab soravtansine infusions. 
Listings will be provided with the information from all of the study drug administration eCRFs 
(including mirvetuximab soravtansine administration, bevacizumab administration, carboplatin 
administration, carboplatin desensitization, pegylated liposomal doxorubicin administration, and 
pembrolizumab administration). 
 
9.2. 
Adverse Events 
Adverse events (AEs), will be documented on the AE eCRF and monitored continuously 
throughout the study from the time of the first dose of study treatment until 30 days after the 
patient’s last study treatment or until the event has resolved, stabilized or an outcome has been 
reached, whichever comes first. AEs attributed to study procedures, including those events that 
occur prior to the first dose, should also be documented on the AE eCRF. Any other change in 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
39 
 
 
medical condition, which occurs during the interval between consent and first dose, will be 
documented on the medical history eCRF. 
For patients who discontinue study treatment due to a study-related AE, the reporting time- 
period may be extended. These patients must be followed at least once a week for four weeks, 
and subsequently at 4-week intervals until resolution or stabilization of the adverse event or 
laboratory abnormality, whichever comes first. 
Adverse event (AE) data are available to ImmunoGen from two sources, the eCRFs and the SAE 
forms. While reconciliation will be performed, the production of data summaries and listings 
will be based on the data collected on the eCRF. 
Pre-treatment AEs are defined as AEs with an onset date prior to the first dose of study drug. 
Treatment-emergent adverse events (TEAEs) are defined as adverse events with an onset date on 
or after the first dose of study drug, and within 30 days of the last dose of study drug (inclusive 
of all treatment periods, primary and SCP treatment if applicable). Medical history conditions 
that exist before the initiation of study treatment but worsen in severity during the study will also 
be recorded on the AE eCRF as an AE, and will be included as treatment-emergent in the 
summary tables and listings. 
The adverse events will be coded using MedDRA (version 21.0 or later), associating lower-level 
terms with preferred terms and system organ classes by the primary hierarchy. The tables will 
display the counts and percentages of patients who reported at least one TEAE in each system 
organ class represented in the AE data. Within each system organ class, the tables will display 
the counts and percentages of patients reporting at least one TEAE as designated by the preferred 
terms. 
AEs are graded using Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03. AE summaries may include summaries for all AEs and by the maximum CTCAE 
grade for the item being summarized (i.e., SOC or PT). In these cases, the outputs will include a 
row for All Grades as well as rows for the 5 potential CTCAE grades: Grade 1 (Mild), Grade 2 
(Moderate), Grade 3 (Severe), Grade 4 (Life threatening or disabling), or Grade 5 (Death). AEs 
missing a severity grade will not be included in the Grade 1-5 rows of the tables. An AE reported 
by a patient more than once will be represented in the most severe category. 
The following AE summaries will be produced: 
• An Overall Summary of Safety will summarize the numbers of patients with TEAEs 
of each grade and the number of patients who died during the study or within 30 days 
of last dose. 
• All TEAEs 
• Serious TEAEs 
• Non-Serious TEAEs (i.e. TEAEs excluding SAEs) 
• Grade 3 or higher TEAEs 
• TEAEs leading to drug withdrawal. This subset includes TEAEs with an Action 
Taken of “Drug Permanently Discontinued.” 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
40 
 
 
• TEAEs related to study drug. This table will include TEAEs with a drug relationship 
of “Possibly Related,” “Probably Related,” “Definitely Related.” It will also include 
TEAEs with missing drug relationships. An AE reported by a patient more than once 
will be included in this table if at least one of the drug association grades is one of the 
grades listed here. 
• Serious, Related TEAEs. This subset includes all serious TEAEs with a drug 
relationship of “Possibly Related,” “Probably Related,” “Definitely Related.” It will 
also include serious TEAEs with missing drug relationships. An AE reported by a 
patient more than once will be included in this table if at least one of the drug 
association grades is one of the grades listed here. 
• TEAEs leading to dose reduction and/or delay 
• Related TEAEs leading to dose reduction and/or delay 
• Deaths on Study or within 30 Days of the Last Dose 
The following AE listings will be produced: 
• All pre-treatment AEs will be listed. 
• All AEs, sorted chronologically within patient. This listing includes system organ 
class, preferred term, onset and end dates, and other relevant information. 
• Serious TEAEs, sorted chronologically within patient. 
• TEAEs leading to drug withdrawal. This subset includes TEAEs with an Action 
Taken of “Drug Permanently Discontinued.” 
• TEAEs related to study drug. This listing will include TEAEs with a drug 
relationship of “Possibly Related,” “Probably Related,” “Definitely Related.” It will 
also include TEAEs with missing drug relationships. 
• Serious TEAEs related to study drug. This listing will include serious TEAEs with a 
drug relationship of “Possibly Related,” “Probably Related,” “Definitely Related.” It 
will also include serious TEAEs with missing drug relationships. 
• TEAEs resulting in death. This listing includes TEAEs with a CTCAE Grade of 
“Grade 5 (Death)” or TEAEs with an outcome of “Fatal”. 
The following groupings of TEAEs will be generated as part of the focused analysis of safety: 
• Ocular TEAEs 
• A list of preferred terms for ocular AE will be provided and finalized by the Sponsor 
before the final database lock. 
• Peripheral Neuropathy TEAEs 
• A list of preferred terms meeting the criteria for peripheral neuropathy will be 
provided and finalized by the Sponsor before the final database lock. 
• Pneumonitis 
For each of the focused safety analysis groups, the following summary tables will be produced: 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
41 
 
 
• TEAEs by SOC, PT, and maximum CTCAE grade. 
• Related TEAEs by SOC, PT, and maximum CTCAE grade. 
• Serious TEAEs by SOC, PT, and maximum CTCAE grade. 
• Related serious TEAEs by SOC, PT, and maximum CTCAE grade. 
Additionally, a table will be produced which contains the following for each of the focused 
safety analysis groups: 
• The number of patients with at least 1 TEAE in each group, presented by treatment 
arm. 
• Time to first onset of each group of TEAEs. 
• Action taken with study drug with respect to each group of TEAEs. 
For the focused safety analysis, the following listings will be produced: 
• Ocular TEAEs. 
• Peripheral neuropathy TEAEs. 
• Pneumonitits TEAE. 
9.3. 
Dose Limiting Toxicities (DLTs) 
DLTs will be defined as a TEAE or abnormal laboratory value related to study treatment (i.e. 
assessed as unrelated to disease, intercurrent illness, or concomitant medications), including 
those TEAEs and abnormal laboratory values that result in a failure to meet the criteria for 
retreatment. DLTs will be considered related to the study treatment unless there is clear evidence 
of an alternative explanation and this attribution is agreed to by the CRC. 
For the purposes of dose escalation and determination of the MTD, only DLTs that occur during 
the first cycle will be necessarily considered for decisions regarding dose escalation. Clinically 
significant toxicities or treatment-emergent adverse events that meet the definition of dose 
limiting but occurring after Cycle 1 (dose modifying events) may be considered when 
determining the MTD. 
A listing of DLTs will be provided. 
 
9.4. 
Clinical Laboratory Results 
Laboratory test results (including hematology, coagulation, serum chemistry, thyroid panel and 
urinalysis) and abnormal laboratory values will be presented in data listings. Common Toxicity 
Criteria (CTCAE) version 4.03 lab grades will also be presented. CTCAE grades will be derived 
based on laboratory results, and will not factor in clinical evaluations. 
Shift tables summarizing the changes from baseline in severity of lab grades will be provided for 
lab parameters that are graded according to the CTCAE v4.03. Summaries of actual values and 
changes from baseline will be presented by treatment group for each assessment time point, 
beginning with the first post-baseline assessment. Grade 3 or above lab values will also be 
summarized based on the worst grade observed on study. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
42 
 
 
Clinically significant values in liver function tests will be summarized by the following 
categories using the maximum value while on treatment. The denominator for the summaries 
will be the number of patients who had at least one non-missing value during treatment. Note 
the categories for each test are not mutually exclusive: 
• Aspartate Aminotransferase (AST) 
− > 3xULN 
− > 5xULN 
− > 10xULN 
− > 20xULN 
• Alanine Aminotransferase (ALT) 
− > 3xULN 
− > 5xULN 
− > 10xULN 
− > 20xULN 
• AST or ALT 
− > 3xULN 
− > 5xULN 
− > 10xULN 
− > 20xULN 
• Total Bilirubin (TBL) 
− > ULN 
− > 2xULN 
• Alkaline Phosphatase (ALP) 
− > 1.5xULN 
• (AST or ALT) and TBL 
− AST or ALT > 3xULN and TBL > 1.5xULN 
− AST or ALT > 3xULN and TBL > 2xULN 
• (AST or ALT) and ALP and TBL 
− AST or ALT > 3xULN and ALP < 2xULN and TBL ≥ 2xULN 
Results from pregnancy tests will be provided in data listings. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
43 
 
 
9.5. 
Vital Signs 
Vital signs (including temperature, pulse rate, systolic blood pressure, diastolic blood pressure, 
respiratory rate and weight) will be presented in data listings. 
 
9.6. 
Electrocardiograms (ECGs) 
ECG results (Rhythm, Heart Rate, PR Interval, RR Interval, QRS Interval, QT Interval, QTcF 
Interval, and classification of Within Normal Limits, Abnormal, Not Clinically Significant, and 
Abnormal, Clinically Significant will be presented in data listings. If a different correction for 
QT is captured in the eCRF, that QTc will also be reported in the listing for that patient along 
with QTcF. 
The number and percent of patients in the following non-mutually exclusive categories will be 
summarized by visit: 
• QTc > 450 ms 
• QTc > 480 ms 
• QTc > 500 ms 
• QTc change from baseline > 30 ms 
• QTc change from baseline > 60 ms 
This summary of QTc will be based on QTcF derived from QT and RR interval, not the QTcF 
value reported in eCRF. 
For numeric results, summaries of actual values and changes from baseline will be presented by 
treatment group for each assessment time point, beginning with Cycle 1 Day 1 End of Infusion 
time point. Note that dosing ECGs are collected in triplicate and analyses for numeric results 
will be based on the average of the triplicate results. 
For the overall ECG result (Within Normal Limits, Abnormal, Not Clinically Significant, and 
Abnormal, Clinically Significant) summaries will be provided for baseline and each post- 
baseline assessment time point. Note that dosing ECGs are collected in triplicate and analyses 
for the overall ECG result will be based on the worst-case result (i.e. if any one of the triplicate 
results is Abnormal, Clinically Significant then the value for the time point will be Abnormal, 
Clinically Significant). The hierarchy for the worst-case assessment is: Abnormal, Clinically 
Significant will be considered the worst value, with Abnormal, Not Clinically Significant being 
considered worse than Within Normal Limits. 
 
9.7. 
Concomitant Medications (CMs) 
All medications and supportive therapy taken within four weeks prior to Cycle 1, Day 1 and 
through 30 days after last study treatment must be recorded on the appropriate electronic case 
report form (eCRF). The identity of all medications, dosage, and route of administration, 
frequency, duration of administration, and indication for use will be recorded in the appropriate 
sections of the eCRF. 
Prior medications are defined as medications with a stop date prior to the first dose of study 
treatment. Concomitant medications are defined as medications which are taken during the 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
44 
 
 
course of study treatment and within 30 days of the last dose of study treatment (inclusive of all 
treatment periods, primary and SCP treatment if applicable). That is, medications started after 
the first dose of study treatment and within 30 days of the last dose of study treatment are 
considered as concomitant medications. Additionally, medications started prior to the first dose 
of study treatment, but with a stop date after the first dose of study treatment and within 30 days 
of the last dose of study treatment will be considered concomitant medications. 
Prior and concomitant medications will be coded using the September 2015 or later version of 
World Health Organization drug dictionary (WHO Drug). Separate summary tables will be 
provided for prior and concomitant medications. Summary tables will be organized to display 
the anatomical main class of each coded medication (ATC level 1 term) and, within that, the 
pharmacological subgroup (ATC level 3 term) of the coded medication. The summary table will 
display counts and percentages of patients who reported using at least 1 medication in each 
represented pharmacological subgroup. If a patient has more than one medication in the 
subgroup, they will be counted only once. 
A complete listing will be generated as well. The listing will contain both prior and concomitant 
medications with an indication of whether the medication is a prior or concomitant medication. 
The listing will display entries from the Concomitant Medications form, ordered within patient 
by the “Start Date.” The listing will display the recorded term from the CRF and, adjacent to 
that, the WHO Drug anatomical main class (ATC level 1 term) and the pharmacological 
subgroup (ATC level 3 term) that appears in the tables. 
 
9.8. 
Concomitant Procedures 
All procedures within four weeks of Cycle 1, Day 1 and through 30 days after last study 
treatment must be recorded on the appropriate electronic case report form (eCRF). 
Prior procedures are defined as procedures with a procedure date that is prior to the first dose of 
study drug. Concomitant procedures are defined as procedures with a procedure date on or after 
the first dose of study drug, and within 30 days of the last dose of study drug (inclusive of all 
treatment periods, primary and SCP treatment if applicable). 
Prior and concomitant procedures will be coded using MedDRA (version 21.0 or later), 
associating lower-level terms with preferred terms and system organ classes by the primary 
hierarchy. 
A complete listing will be generated. The listing will contain both prior and concomitant 
procedures with an indication of whether the procedure is a prior or concomitant procedure. The 
listing will display entries from the Concomitant Procedures form, ordered within patient by the 
“Date of Procedure.” The listing will display the recorded term from the CRF and, adjacent to 
that, the system organ class and the preferred term that appears in the tables. 
 
9.9. 
Ophthalmic Examinations 
Ophthalmic Examinations are collected at the Screening, End of Treatment and 30-Day Follow- 
up Visits. Results of the Ophthalmic Examinations will be presented in data listings. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
45 
 
 
9.10. 
Ocular Symptom Assessments 
Results of the Ocular Assessments will be presented in data listings. 
 
9.11. 
Corticosteroid and Lubricating Eye Drop Compliance 
All compliance information collected on the eCRF will be presented in data listings. 
 
9.12. 
Transfusions 
All Transfusions recorded on the eCRF will be presented in data listings. 
 
9.13. 
Physical Examination 
Physical Examination results will be presented in data listings. 
 
9.14. 
Pulmonary Function Tests 
Pulmonary Function Text results will be presented in data listings. 
 
9.15. 
Pulse Oximetry 
Pulse Oximetry will be presented in data listings. 
 
9.16. 
Eastern Cooperative Oncology Group Performance Status (ECOG 
PS) 
Eastern Cooperative Oncology Group performance status (ECOG PS) results will be presented in 
data listings. ECOG PS at baseline will be presented in summary table of baseline disease 
characteristics. 
9.17. 
ECHO/MUGA 
ECHO/MUGA scans are taken on for patients receiving pegylated liposomal doxorubicin. All 
ECHO/MUGA results will be presented in data listings. 
 
9.18. 
24 Hour Urine Protein 
All 24 hour urine protein results will be presented in data listings. 
 
10. 
IMMUNOGENICITY 
The potential immunogenicity against mirvetuximab soravtansine will be assessed at various 
timepoints in Cycles 1 through 6, as outlined in Protocol Section 6.2 and Protocol Appendix F. 
Exploratory analyses will be completed to evaluate the potential impact of immunogenicity on 
PK, safety, and efficacy. 
The anti-drug antibody (ADA) analyses, including the impact of immunogenicity on PK, will be 
covered by a separate, independent analysis plan (Section 12). 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
46 
 
 
Impact of immunogenicity on safety and efficacy will be explored. A by patient TEAE listing for 
those patients determined seropositive for IMGN853 antibodies will be produced. Summary of 
TEAEs experienced within 1 and 3 days of ADA+ will be generated for those patients who sero- 
convert following the first dose of mirvetuximab soravtansine. Efficacy will be analysed by 
seroconversion status for patients treated with IMGN853, as appropriate. 
 
11. 
BIOMARKERS 
The biomarker analyses for this study will be covered by a separate, independent analysis plan. 
 
12. 
PHARMACOKINETICS 
Pharmacokinetic analyses for this study will be covered by a separate, independent analysis plan. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
47 
 
 
REFERENCES 
Bevacizumab [package insert]. South San Franciso, CA: Genentech, Inc.; 2014. 
Moore K, Martin L, Matulonis U, Konner J, Seward S, Bauer T, O’Malley, Perez R, Woondong 
J, Zhou Y, Kirby M, Mohanavelu, S, Ruiz-Soto R, Birrer M. IMGN853 (mirvetuximab 
soravtansine), a Folate Receptor Alpha (FRα)-targeting Antibody-drug Conjugate (ADC): Single 
Agent Activity in Platinum-resistant Epithelial Ovarian Cancer (EOC) Patients. ASCO 2016. 
Abstract #5567. 
Varga A, Piha-Paul SA, Ott PA, et al. Antitumor activity and safety of pembrolizumab in 
patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib 
study. J Clin Oncol 33, (suppl; abstr 5510) 2015. 


ImmunoGen, Inc. Protocol: 0402 
IQVIA Biotech (Confidential) Project # OXA69059 
48 
 
 
APPENDIX 1: TEMPLATE SAS® CODE 
This appendix provides template SAS® code (version 9.3 or higher) that will be used for 
analysis. 
Template code for the ORR, DCR, and GCIG CA125 response estimates along with the 95% 
confidence intervals: 
proc freq data=AD_RESP; 
by TRTP; 
tables AVAL / binomial alpha=0.05; 
run; 
Template code for median time-to-event estimates along with 95% confidence intervals: 
proc lifetest data=AD_TTE; 
time AVAL*CNSR(1); 
strata TRTP; 
run; 
where:  
• AD_RESP is the name of the ADaM dataset used for response analysis 
• AD_TTE is the name of the ADaM dataset used for time-to-event analysis 
• TRTP is a variable containing the treatment used for analysis. 
• AVAL is a variable containing the value for analysis (e.g. objective response or time 
to death) 
• CNSR is a variable indicating whether the AVAL is censored (1=censored, 0=non- 
censored)