Clinical trial NCT04209855
Conditions: Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer
Keywords: Platinum-resistant Folate-receptor alpha expression Phase 3 Antibody-drug conjugate mirvetuximab soravtansine IMGN853 Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer
Sponsor: AbbVie
Start date: 2019-12-31; Completion date: 2024-10-29
Enrollment: 453 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This Phase 3 study is designed to compare the efficacy and safety of mirvetuximab soravtansine (MIRV) vs. IC chemotherapy in participants with platinum-resistant high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα. Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. The FRα positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay.

Detailed description:
Participants will be randomized to either MIRV or IC chemotherapy (paclitaxel, PEGylated liposomal doxorubicin, or topotecan).

Arms: arm 1: Participants will receive single-agent mirvetuximab soravtansine (MIRV) at 6 milligrams (mg)/kilogram (kg) adjusted ideal body weight (AIBW) administered intravenously (IV) on Day 1 of every 3-week cycle (Q3W). arm 2: Participants will receive a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel administered at 80 milligrams/square meter (mg/m\^2) as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week cycle; or topotecan administered at 4 mg/m\^2 over 30 minutes on Days 1, 8, and 15 of a 4-week cycle. Alternatively, topotecan could be administered at 1.25 mg/m\^2 over 30 minutes on Days 1 to 5 of a 3-week cycle; or pegylated liposomal doxorubicin administered at 40 mg/m\^2 as a 1 mg/minute IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, pegylated liposomal doxorubicin could be administered as a 1-hour infusion.
Interventions: intervention 1: Mirvetuximab Soravtansine intervention 2: Paclitaxel intervention 3: Topotecan intervention 4: Pegylated liposomal doxorubicin
Intervention descriptions: intervention 1: Mirvetuximab Soravtansine will be administered per dose and schedule specified in the arm. intervention 2: Paclitaxel will be administered per dose and schedule specified in the arm. intervention 3: Topotecan will be administered per dose and schedule specified in the arm. intervention 4: Pegylated liposomal doxorubicin will be administered per dose and schedule specified in the arm.

Protocol documents:
Prot_000.pdf: 




Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
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SPONSOR CONTACT LIST 
Primary Medical Monitor 
  
Phone: 
  
Email: 
 
Clinical Scientist 
Brooke 
 
Phone: 
 
Email: 
 
Trial Management  
 
Phone: 
 
Email: 
 
 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
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INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator Brochure for mirvetuximab soravtansine. I have read 
the ImmunoGen Protocol IMGN853-0416 and agree to conduct the study as outlined and in 
conformance with International Conference on Harmonisation (ICH) E6 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 of Investigator 
 
Signature of Investigator 
Date 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
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LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Term 
ADA 
anti-drug antibodies 
ADC 
antibody drug conjugate 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
AIBW 
adjusted ideal body weight 
ALT 
alanine aminotransferase (SGPT) 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase (SGOT) 
BICR 
blinded independent central review 
BRCA 
breast cancer susceptibility gene 
BSA 
body surface area 
BUN 
blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CNS 
central nervous system 
CR 
complete response/remission 
CRO 
contract research organization 
CT 
computed tomography 
CTCAE  
Common Terminology Criteria for Adverse Events 
DM4 
N2’-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2’-
deacetylmaytansine 
S-methyl DM4 
methylated N2’-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-sulfopentyl]-
N2’-deacetylmaytansine 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
ECHO 
echocardiography 


Mirvetuximab Soravtansine (IMGN853) 
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Abbreviation 
Term 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EOC 
epithelial ovarian cancer 
EORTC 
European Organisation for Research and Treatment of Cancer 
EOS 
End of Study 
EOT 
End of Treatment 
EPO 
erythropoietin 
FDA 
Food and Drug Administration 
FFPE 
formalin fixed paraffin embedded 
FIH 
first-in-human 
FOLR1, FRα 
folate receptor 1/folate receptor alpha 
GCIG 
Gynecologic Cancer Intergroup  
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony stimulating factor 
HFS 
hand-foot syndrome 
HIV 
human immunodeficiency virus 
IA 
interim analysis 
IC 
investigator’s choice 
IC50 
half maximal (50%) inhibitory concentration 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation  
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IHC 
immunohistochemistry 
ILD 
interstitial lung disease 
IMGN 
ImmunoGen 
IND 
Investigational New Drug  
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
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Abbreviation 
Term 
ITT 
intent-to-treat 
IV 
intravenous 
LVEF 
left ventricular ejection fraction 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIRV 
mirvetuximab soravtansine (IMGN853) 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MUGA scan 
multigated acquisition scan 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
nM 
nanomolar 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 
PD 
progressive disease 
PE 
physical examination 
PET 
positron emission testing 
PFS 
progression-free survival 
PFS2 
time to second disease progression  
PGIS 
Patient global impression of severity  
PK 
pharmacokinetics 
PLD 
pegylated liposomal doxorubicin 
PLT 
platelets 
PR 
partial response/remission 
PRO 
patient-reported outcomes 
PROC 
platinum-resistant ovarian cancer 
PS 
performance status 
PT 
prothrombin time 
Q3W 
every 3 weeks 
Q4W 
every 4 weeks 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
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Abbreviation 
Term 
QoL 
quality of life 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended phase 2 dose 
RR 
response rate 
RT 
radiotherapy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
Steering Committee 
SD 
stable disease 
SGOT 
serum glutamic oxaloacetic transaminase (AST) 
SGPT 
serum glutamic pyruvic transaminase (ALT) 
SoD 
sum of diameters 
SOC 
System Organ Class 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TAb 
total antibody 
TEAE 
treatment emergent adverse events 
TPR 
time point response 
ULN 
upper limit of normal 
US 
United States 
WBC 
white blood cell (count) 
WCBP 
woman of childbearing potential 
WHO 
World Health Organization 
WHO-DD 
World Health Organization –Drug Dictionary 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
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9 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: ImmunoGen, Inc. 
Name of Investigational Product: mirvetuximab soravtansine (MIRV; IMGN853) 
Name of Active Ingredient: mirvetuximab soravtansine (MIRV; IMGN853) 
Title of Study: MIRASOL: A Randomized, Open-label, Phase 3 Study of Mirvetuximab Soravtansine 
vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial 
Ovarian, Primary Peritoneal, or Fallopian Tube Cancers with High Folate Receptor-Alpha Expression 
Number of Patients (planned): Approximately 430 patients 
Study Center(s): Approximately 200 centers globally 
Studied Period (months): Approximately 30 months 
(including follow-up) 
Phase of Development: 3 
Objectives: 
Primary Objective: 
• 
To compare the progression-free survival (PFS) of patients randomized to mirvetuximab 
soravtansine (MIRV) vs. Investigator’s choice of chemotherapy (IC Chemo)  
Key Secondary Objectives: 
• 
To compare the objective response rate (ORR) of patients randomized to MIRV vs. IC Chemo 
• 
To compare overall survival (OS) of patients randomized to MIRV vs. IC Chemo  
• 
To compare the primary patient-reported outcome (PRO) using the European Organization for 
Research and Treatment of Cancer (EORTC) QLQ-OV28 (Abdominal/GI Symptom Scale) 
assessment from patients randomized to MIRV vs. IC Chemo 
Additional Secondary Objectives: 
• 
To compare the safety and tolerability of MIRV vs. IC Chemo  
• 
To compare the duration of response (DOR) in patients randomized to MIRV vs. IC Chemo 
• 
To compare the CA-125 response rate (RR) per Gynecologic Cancer Intergroup (GCIG) CA-
125 criteria in patients randomized to MIRV vs. IC Chemo  
• 
To compare the time to progression or death on the next line of treatment (PFS2) in patients 
randomized to MIRV vs. IC Chemo  
Exploratory Objectives: 
• 
To assess PRO using the EORTC QLQ-C30, EuroQol-5 Dimension 5-level (EQ-5D-5L), and 
Patient Global Impression of Severity (PGIS) questionnaires  
• 
To evaluate concentrations of MIRV, total antibody (TAb), DM4 and S-methyl DM4, using 
sparse sampling 
• 
To assess the immunogenicity of MIRV via anti-drug antibodies (ADAs)  
• 
To evaluate potential biomarkers in blood and tumor tissue predictive of response to MIRV  


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
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Study Design Overview and Schema: 
This Phase 3 study is designed to compare the efficacy and safety of MIRV vs. IC Chemo in patients 
with platinum-resistant high-grade epithelial ovarian cancer (EOC), primary peritoneal, or fallopian 
tube cancer, whose tumors express a high-level of FRα. Patients will be, in the opinion of the 
Investigator, appropriate for single-agent therapy for their next line of therapy. Folate receptor alpha 
(FRα) positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay. 
Eligible patients (N = 430), who have provided informed consent and meet study entry criteria will be 
randomized (1:1) to one of two arms:  
• 
Arm 1 (n = 215): MIRV 6 mg/kg adjusted ideal body weight (AIBW) every 3 weeks (Q3W)  
• 
Arm 2 (n = 215): IC Chemo, at one of the following regimens as determined by the 
Investigator prior to randomization:  
– 
Paclitaxel (Pac; 80 mg/m2) administered QW within a 4-week cycle  
– 
Pegylated liposomal doxorubicin (PLD; 40 mg/m2) administered Q4W  
– 
Topotecan (Topo; 4 mg/m2) administered either on Days 1, 8, and 15 every 4 weeks or for 
5 consecutive days (1.25 mg/m2 Days 1–5) Q3W  
Patients will be stratified by: 
• 
Number of prior lines of therapy (1 vs. 2 vs. 3) 
• 
IC Chemo (Pac vs. PLD vs. Topo) chosen prior to randomization  
The table below shows the dose and schedule of the study drugs. 
Group 
Drug 
Dose 
Dosing Schedule 
Arm 1 
MIRV 
6 mg/kg AIBW IV 
Day 1 of a 3-week cycle  
Arm 2 
Pac 
80 mg/m2 IV 
Days 1, 8, 15, and 22 of a 4-week cycle 
PLD 
40 mg/m2 IV 
Day 1 of a 4-week cycle 
Topo  
4 mg/m2 IV 
Days 1, 8, and 15 of a 4-week cycle 
Topo  
1.25 mg/m2 IV  
Days 1 to 5 of a 3-week cycle  
Disease progression will be evaluated by the Investigator using Response Evaluation Criteria in Solid 
Tumors (RECIST, version 1.1, Appendix B). Computerized tomography (CT) or magnetic resonance 
imaging (MRI) scans will be collected and held for sensitivity analysis by a blinded independent 
central review (BICR). 
Patients will continue to receive study drug until disease progression, unacceptable toxicity, 
withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first).  
Tumor assessments, including radiological assessments by CT/MRI scans will be performed at 
Screening and subsequently every 6 weeks (± 1 week) from Cycle 1 Day 1 (C1D1) (for all regimens) 
for the first 36 weeks then every 12 weeks (± 3 weeks) until disease progression, death, the initiation of 
subsequent anticancer therapy, or patient’s withdrawal of consent, whichever occurs first.  
Patients who discontinue study treatment for reasons other than progressive disease (PD) will continue 
with tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever 
comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments should occur every 6 weeks 
(± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. 
After Week 36, assessment will occur every 12 weeks (± 3 weeks) until documentation of PD or the 
start of new anticancer therapy.  


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
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All patients who discontinue study drug will be followed for survival every 3 months (± 1 month) until 
death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (EOS) 
whichever comes first. Additional survival follow-up calls may occur periodically if needed. All 
patients will be followed for progression and survival.  
Two interim analyses will be conducted, (1) an interim futility analysis (PFS only) when at least 110 
PFS events have occurred, and (2) an interim analysis for OS at the time of final analysis of PFS when 
at least 330 PFS events have occurred. The final analysis for OS will be conducted when at least 300 
deaths have occurred. 
Study Eligibility  
Inclusion Criteria 
1. Female patients ≥ 18 years of age 
2. Patients must have a confirmed diagnosis of high-grade serous EOC, primary peritoneal 
cancer, or fallopian tube cancer  
3. Patients must have platinum-resistant disease:  
a. Patients who have only had 1 line of platinum based therapy must have received at 
least 4 cycles of platinum, must have had a response (CR or PR) and then progressed 
between > 3 months and ≤ 6 months after the date last dose of platinum 
b. Patients who have received 2 or 3 lines of platinum therapy must have progressed on 
or within 6 months after the date of the last dose of platinum  
Note: Progression should be calculated from the date of the last administered dose of 
platinum therapy to the date of the radiographic imaging showing progression  
Note: Patients who are platinum-refractory during front-line treatment are excluded (see 
exclusion criteria) 
4. Patients must have progressed radiographically on or after their most recent line of therapy 
5. Patients must be willing to provide an archival tumor tissue block or slides, or undergo 
procedure to obtain a new biopsy using a low risk, medically routine procedure for 
immunohistochemistry (IHC) confirmation of FRα positivity  
6. Patient’s tumor must be positive for FRα expression as defined by the Ventana FOLR1 
(FOLR-2.1) CDx assay 
7. Patients must have at least one lesion that meets the definition of measurable disease by 
RECIST v1.1 (radiologically measured by the Investigator) 
8. Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer 
therapy, and for whom single-agent therapy is appropriate as the next line of treatment: 
a. Adjuvant ± neoadjuvant considered one line of therapy 
b. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the 
preceding line of therapy (ie, not counted independently) 
c. Therapy changed due to toxicity in the absence of progression will be considered as part of 
the same line (ie, not counted independently) 
d. Hormonal therapy will be counted as a separate line of therapy unless it was given as 
maintenance 
9. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 
0 or 1 
10. Time from prior therapy: 
a. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter) 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
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b. Focal radiation completed at least 2 weeks prior to first dose of study drug 
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related 
toxicities 
12. Major surgery must be completed at least 4 weeks prior to first dose and have recovered or 
stabilized from the side effects of prior surgery 
13. Patients must have adequate hematologic, liver, and kidney functions defined as: 
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL) without G-CSF in the prior 10 
days or long-acting WBC growth factors in the prior 20 days 
b. Platelet count ≥ 100 x 109/L (100,000/μL) without platelet transfusion in the prior 10 days 
c. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 
days 
d. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) 
e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN  
f. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are 
eligible if total bilirubin < 3.0 x ULN) 
g. Serum albumin ≥ 2 g/dL 
14. Patients or their legally authorized representative must be willing and able to sign the informed 
consent form (ICF) and to adhere to the protocol requirements 
15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive 
method(s) (as defined Section 5.9.6) in while on study drug and for at least 3 months after the 
last dose of MIRV or at least 6 months after the last dose of Pac, PLD, or Topo 
16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug 
Exclusion Criteria  
1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors 
containing any of the above histologies, or low-grade or borderline ovarian tumor 
2. Patients with primary platinum-refractory disease, defined as disease that did not respond to 
(CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing 
chemotherapy 
3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow 
4. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse 
Events (CTCAE) 
5. Patients with active or chronic corneal disorders, history of corneal transplantation, or active 
ocular conditions requiring ongoing treatment/monitoring such as uncontrolled glaucoma, wet 
age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy 
with macular edema, macular degeneration, presence of papilledema, and /or monocular vision 
6. Patients with serious concurrent illness or clinically relevant active infection, including, but 
not limited to the following: 
a. Active hepatitis B or C infection (whether or not on active antiviral therapy)  
b. HIV infection 
c. Active cytomegalovirus infection  
d. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before 
starting study drug 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
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Note: Testing at screening is not required for the above infections unless clinically 
indicated 
7. Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-
Eaton syndrome (paraneoplastic syndrome) 
8. Patients with clinically significant cardiac disease including, but not limited to, any one of the 
following: 
a. Myocardial infarction ≤ 6 months prior to first dose 
b. Unstable angina pectoris 
c. Uncontrolled congestive heart failure (New York Heart Association > class II) 
d. Uncontrolled ≥ Grade 3 hypertension (per CTCAE) 
e. Uncontrolled cardiac arrhythmias 
9. Patients assigned to PLD stratum only:  
• 
Left ventricular ejection fraction (LVEF) below the institutional limit of normal as 
measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan  
10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to 
randomization 
11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 
12. Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), 
including noninfectious pneumonitis 
13. Patients with required use of folate-containing supplements (eg, folate deficiency) 
14. Patients with prior hypersensitivity to monoclonal antibodies 
15. Women who are pregnant or lactating 
16. Patients with prior treatment with MIRV or other FRα-targeting agents 
17. Patients with untreated or symptomatic central nervous system (CNS) metastases 
18. Patients with a history of other malignancy within 3 years prior to randomization  
Note: does not include tumors with a negligible risk for metastasis or death (eg, adequately 
controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of 
the cervix or breast) 
19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients 
20. People who are detained through a court or administrative decision, receiving psychiatric care 
against their will, adults who are the subject of a legal protection order (under 
tutorship/curatorship), people who are unable to express their consent, and people who are 
subject to a legal guardianship order 
21. Simultaneous participation in another research study, in countries or localities where this is the 
health authority guidance 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
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Prohibited Concomitant Medications:  
Any non-study anticancer agents, including but not limited to antineoplastic agents, biologics, 
monoclonal antibodies (mAb), and hormonal therapy, or palliative radio therapy (RT) during study 
treatment. 
Investigational Product, Dosage and Mode of Administration:  
Patients randomized to MIRV receive a dose of 6 mg/kg AIBW IV Q3W.  
Reference Therapy, Dosage, and Mode of Administration:  
Pac will be administered at 80 mg/m2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week 
cycle.  
PLD will be administered at 40 mg/m2 as a 1 mg/min IV infusion on Day 1 of a 4-week cycle. After 
Cycle 1, if tolerated, PLD may be delivered as a 1-hour infusion. 
Topo will be administered at 4 mg/m2 as a 30 min IV infusion on Days 1, 8, and 15 of a  
4-week cycle. Alternatively, Topo can be administered at 1.25 mg/m2 over 30 min on Days 1 to 5 of a 
3-week cycle.  
The dose of chemotherapeutic agents will be calculated using body surface area (BSA). Institutional 
conventions may be used to calculate BSA. 
Duration of Study Participation:  
The duration of study participation for each patient extends from the signing of the ICF until the final 
follow-up study visit, termination from study, death, or withdrawal of consent.  
Study Committees: 
An Independent Data Monitoring Committee (IDMC) will independently evaluate safety data of 
patients enrolled to the study, as well as the interim futility analysis. The structure of the committee, 
frequency of meetings and responsibilities are outlined in an IDMC charter. 
 






Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
Confidential and Proprietary 
ImmunoGen, Inc. 
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Abbreviations: AE = adverse event; aPTT = activated partial thromboplastin time; C = cycle; CA = cancer antigen; D = day; ECOG = Eastern Cooperative Oncology Group; 
ECG = electrocardiogram; EOT = End of Treatment; FFPE = formalin-fixed-paraffin-embedded; INR = international normalized ratio; PK = pharmacokinetics; PRO = patient-
reported outcome; PT = prothrombin time; SAE = serious adverse event. 
a Must be within 28 days before C1D1. 
b Confirm before first dose. 
c Must be within 14 days before C1D1. 
d ECG and PRO assessment may be performed predose at C1D1 if not performed previously during screening.  
e Testing for FRα expression is required for all patients. Those who do not have archival tumor tissue to submit will be required to undergo procedures to obtain a new biopsy 
during the Pre-Screening period to confirm eligibility. If the archival tumor tissue does not meet FRα criteria, a new biopsy tumor sample may be submitted and used to meet this 
criterion. 
f Full physical examination (PE) is required at Screening and the 30-day Follow-up visit. Symptom-directed PEs while on study drug. 
g ECOG, PE, pregnancy, hematology, and chemistry labs (if all parameters are within normal range) do not need to be repeated at C1D1 if performed within the previous 4 days 
during Screening.  
h Vital signs (BP and temperature) will be measured before start of infusion; post infusion vital signs should be collected as clinically indicated for potential infusion related 
reaction. 
i Hematology and chemistry labs may be performed up to 4 days prior Day 1 of each cycle, and as clinically indicated while on treatment, with results reviewed before each drug 
administration. In the event of severe toxicity, laboratory tests must be repeated as clinically necessary until the toxicity resolves or stabilizes to baseline level.  
j For women of childbearing potential (WCBP), a urine or serum pregnancy test will be performed within 4 days prior to Day 1 of each cycle and at the 30-day Follow-Up visit. It 
is recommended to perform monthly pregnancy tests for 3 months after the last dose of MIRV. Additional testing may be performed in accordance with institutional 
requirements or local regulation. 
k Baseline ophthalmic exams will be performed by an ophthalmologist within 14 days before C1D1 and will include the following: visual acuity (with/without corrective lens; 
whichever best reflects the patient’s usual functioning), slit lamp examination, intraocular pressure measurement, and indirect fundoscopy. All patients who had an ophthalmic 
exam on study treatment (post-baseline) will have a complete ophthalmological examination performed at EOT visit or 30 day follow-up visit. 
l Ocular symptoms assessment will be performed by the treating physician or other qualified individual before the start of each cycle. For patients reporting > CTCAE Grade 1 
ocular symptoms, treatment will be held until the patient is evaluated by an ophthalmologist for a complete examination.  
m Radiologic tumor assessment by CT/MRI scan.  
n If a patient discontinues before documentation of progressive disease (PD), a tumor assessment and CA-125 will be assessed at the EOT visit or 30-day Follow-up visit, if not 
performed within the previous 6 weeks. Tumor assessments and CA-125 will continue to be performed. Patients who discontinue study treatment for reasons other than 
progressive disease (PD) will continue tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever comes first. Prior to Week 36 (from 
Cycle 1, Day 1), assessments should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. After Week 36, 
assessment will occur every 12 weeks (± 3 weeks) until documentation of PD, death, the start of new anticancer therapy, or patient’s withdrawal of consent (whichever comes 
first). 
o CA-125 responses will be confirmed according to GCIG criteria.  
p Includes the EQ5D-5L, QLQ-C30, QLQ-OV28, and PGIS assessments. At visits where administered, the PROs should be completed before other procedures at the beginning of 
clinic visit. PRO assessments will occur Day 1 of every cycle up to Week 24 and then approximately every 12 weeks (± 3 weeks), at the time of tumor assessment, until 
documentation of PD or the start of new anticancer therapy. 
q Only AEs/SAEs which are considered related to a study procedure (ie blood draw or fresh tumor biopsy) will be captured during the Pre-screening period, ie from the time of 
signing the Pre-screening consent (if one is utilized) until the signing of the main study informed consent, or until the patient is determined to be a screen failure. 
r All ocular AEs will be followed until resolution, stabilization, or return to baseline. 
s Blood samples for PK analysis will be taken within 1 hour after MIRV infusion on Day 1 of Cycles 1 and 3, and on Day 8 (± 24 hours) of Cycles 1 and 3. Samples will also be 
collected on the day of MIRV infusion prior to dosing on Day 1 of Cycles 2 and 4, EOT, and also at the 30-Day Follow-up if feasible. 
t Immunogenicity will be assessed in PK samples collected prior to dosing (predose) on C2D1, C4D1, and anytime at EOT, and 30-day Follow-up.  There will be an ADA only 
collection prior to dosing on Day 1 of Cycle 1. 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
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u Survival follow-up assessments will occur every 3 months (±1 month) until death, the patient is lost to follow-up or withdraws of consent for survival follow-up, or EOS, 
whichever comes first. These assessments may be conducted by telephone. Information on initiation of other anticancer therapy (including start date, therapy type/name, and 
response on treatment) should be collected. Additional survival follow-up calls may occur periodically if needed. 
Note: A patient’s BRCA mutational status (germline or somatic mutation in tumor tissue) will be collected as part of her medical history if available. Patients without a known 
mutation will be classified as unknown. Testing may be performed to support exploratory endpoints at the end of the trial; however, results will not be communicated to treating 
physicians or patients.  






Mirvetuximab Soravtansine (IMGN853) 
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d ECG and PRO assessment may be performed predose at C1D1 if not performed previously during screening.  
e Testing for FRα expression is required for all patients. Those who do not have archival tumor tissue to submit will be required to undergo procedures to obtain a new biopsy 
during the Pre-Screening period to confirm eligibility. If the archival tumor tissue does not meet FRα criteria, a new biopsy tumor sample may be submitted and used to meet this 
criterion. 
f Full examination (PE) is required at Screening and the 30-day Follow-up visit. Symptom-directed PEs while on study drug. 
g PE, pregnancy, hematology, and chemistry labs (if all parameters are within normal range) do not need to be repeated at C1D1 if performed within the previous 4 days during 
Screening. 
h Vital signs (BP and temperature) will be measured before start of infusion; post infusion vital signs should be collected as clinically indicated for potential infusion related 
reaction. 
i ECOG does not need to be repeated at C1D1 if performed within the previous 4 days during Screening.  
j Hematology and chemistry labs may be performed up to 4 days prior Day 1 of each cycle, and as clinically indicated while on treatment, with results reviewed prior to each drug 
administration. In the event of severe toxicity, laboratory tests must be repeated as clinically necessary until the toxicity resolves or stabilizes to baseline level.  
k For WCBP, a urine or serum pregnancy test will be performed within 4 days prior to Day 1 of each cycle and at the 30-day Follow-Up visit. It is recommended to perform 
monthly pregnancy tests for 6 months after the last dose of chemotherapy. Additional testing may be performed in accordance with institutional requirements or local regulation. 
l Baseline ophthalmic exams will be performed by an ophthalmologist within 14 days before C1D1 and will include the following: visual acuity (with/without corrective lens; 
whichever best reflects the patient’s usual functioning), slit lamp examination, intraocular pressure measurement, and indirect fundoscopy. All patients who had an ophthalmic 
exam on study treatment (post-baseline) will have a complete ophthalmologic exam performed at the EOT visit or 30-Day Follow-up visit. 
m Ocular symptoms assessment will be performed by the treating physician or other qualified individual at screening and as clinically indicated if symptoms appear on study. For 
patients reporting > CTCAE Grade 1 ocular symptoms, treatment will be held until the patient is evaluated by an ophthalmologist for a complete examination.  
n Radiologic tumor assessment by CT/MRI scan.  
o If a patient discontinues before documentation of PD, a tumor assessment and CA-125 will be assessed at the EOT visit or 30-day Follow-up visit, if not performed within the 
previous 6 weeks. Tumor assessments and CA-125 will continue to be performed. Patients who discontinue study treatment for reasons other than progressive disease (PD) will 
continue tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments 
should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. After Week 36, assessment will occur every 12 
weeks (± 3 weeks) until documentation of PD, death, the start of new anticancer therapy, or patient’s withdrawal of consent (whichever comes first).  
p CA-125 responses will be confirmed according to GCIG criteria.  
q Includes the EQ5D-5L, QLQ-C30, QLQ-OV28, and PGIS assessments. At visits where administered, the PROs should be completed before other procedures at the beginning of 
clinic visit. PRO assessments will occur Day 1 of every cycle up to Week 24 and then approximately every 12 weeks (± 3 weeks), at the time of tumor assessment, until 
documentation of PD or the start of new anticancer therapy. 
r Topo administered daily on Days 1-5; no assessments are required on Days 2-5 unless clinically indicated. 
s Only AEs/SAEs which are considered related to a study procedure (ie blood draw or fresh tumor biopsy) will be captured during the Pre-screening period, ie from the time of 
signing the Pre-screening consent (if one is utilized) until the signing of the main study informed consent, or until the patient is determined to be a screen failure. 
t Survival follow-up assessments will occur every 3 months (±1 month) until death, the patient is lost to follow-up or withdraws of consent for survival follow-up, or EOS, 
whichever comes first. These assessments may be conducted by telephone. Information on initiation of other anticancer therapy (including start date, therapy type/name, and 
response on treatment) should be collected. Additional survival follow-up calls may occur periodically if needed. 
Note: A patient’s BRCA mutational status (germline or somatic mutation in tumor tissue) will be collected as part of her medical history if available. Patients without a known 
mutation will be classified as unknown. Testing may be performed to support exploratory endpoints at the end of the trial; however, results will not be communicated to treating 
physicians or patients. 








Mirvetuximab Soravtansine (IMGN853) 
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i Vital signs (BP and temperature) will be measured before start of infusion; post infusion vital signs to be collected as clinically indicated for potential infusion related reactions. 
Vital signs should only be collected on dosing days, thus for patients randomized to PLD, this would only be on D1 of each cycle, and for patients on Topo, this would be on D1, 
D8, and D15.  
j ECOG does not need to be repeated at C1D1 if performed within the previous 4 days during Screening.  
k Hematology and chemistry labs may be performed up to 4 days prior Day 1 of each cycle, and as clinically indicated while on treatment, with results reviewed before each drug 
administration. In the event of severe toxicity, laboratory tests must be repeated as clinically necessary until the toxicity resolves or stabilizes to baseline level.  
l For WCBP, a urine or serum pregnancy test will be performed within 4 days prior to Day 1 of each cycle and at the 30-day Follow-Up visit. It is recommended to perform 
monthly pregnancy tests for 6 months after the last dose of chemotherapy. Additional testing may be performed in accordance with institutional requirements or local regulation. 
m Baseline ophthalmic exams will be performed by an ophthalmologist within 14 days prior to C1D1 and will include the following: visual acuity (with/without corrective lens; 
whichever best reflects the patient’s usual functioning), slit lamp examination, intraocular pressure measurement, and indirect fundoscopy. All patients who had an ophthalmic 
exam on study treatment (post-baseline) will have a complete ophthalmologic exam performed at the EOT visit or 30-Day Follow-up visit. 
n Ocular symptoms assessment will be performed by the treating physician or other qualified individual at screening and as clinically indicated if symptoms appear on study. For 
patients reporting > CTCAE Grade 1 ocular symptoms, treatment will be held until the patient is evaluated by an ophthalmologist for a complete examination.  
o Radiologic tumor assessment by CT/MRI scan.  
p If a patient discontinues before documentation of PD, a tumor assessment and CA-125 will be assessed at the EOT visit or 30-day Follow-up visit, if not performed within the 
previous 6 weeks. Tumor assessments and CA-125 will continue to be performed. Patients who discontinue study treatment for reasons other than progressive disease (PD) will 
continue tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments 
should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. After Week 36, assessment will occur every 
12 weeks (± 3 weeks) until documentation of PD, death, the start of new anticancer therapy, or patient’s withdrawal of consent (whichever comes first).  
q CA-125 responses will be confirmed according to GCIG criteria.  
r Includes the EQ5D-5L, QLQ-C30, QLQ-OV28, and PGIS assessments. At visits where administered, the PROs should be completed before other procedures at the beginning of 
clinic visit. PRO assessments will occur Day 1 of every cycle up to Week 24 and then approximately every 12 weeks (± 3 weeks), at the time of tumor assessment, until 
documentation of PD or the start of new anticancer therapy. 
s Only AEs/SAEs which are considered related to a study procedure (ie blood draw or fresh tumor biopsy) will be captured during the Pre-screening period, ie from the time of 
signing the Pre-screening consent (if one is utilized) until the signing of the main study informed consent, or until the patient is determined to be a screen failure. 
t Survival follow-up assessments will occur every 3 months (±1 month) until death, the patient is lost to follow-up or withdraws of consent for survival follow-up, or EOS, 
whichever comes first. These assessments may be conducted by telephone. Information on initiation of other anticancer therapy (including start date, therapy type/name, and 
response on treatment) should be collected. Additional survival follow-up calls may occur periodically if needed. 
Note: A patient’s BRCA mutational status (germline or somatic mutation in tumor tissue) will be collected as part of her medical history if available. Patients without a known 
mutation will be classified as unknown. Testing may be performed to support exploratory endpoints at the end of the trial; however, results will not be communicated to treating 
physicians or patients. 


Mirvetuximab Soravtansine (IMGN853) 
Dated 04 December 2020 
Protocol Number IMGN853-0416 
 
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TABLE OF CONTENTS 
SPONSOR SIGNATURE PAGE ................................................................................................ 2 
SPONSOR CONTACT LIST ...................................................................................................... 3 
INVESTIGATOR’S AGREEMENT ........................................................................................... 4 
LIST OF ABBREVIATIONS...................................................................................................... 5 
PROTOCOL SYNOPSIS ............................................................................................................ 9 
1. 
INTRODUCTION .................................................................................................. 34 
1.1. 
Target Background ................................................................................................. 34 
1.2. 
Mirvetuximab Soravtansine .................................................................................... 34 
1.3. 
Epithelial Ovarian Cancer ....................................................................................... 35 
1.4. 
Current Therapies ................................................................................................... 36 
1.5. 
Non-Clinical Studies of Mirvetuximab Soravtansine ............................................... 37 
1.5.1. 
Correlation of FRα Expression with MIRV Activity ............................................... 37 
1.5.2. 
Pharmacology ......................................................................................................... 37 
1.5.3. 
Pharmacokinetics .................................................................................................... 37 
1.5.4. 
Toxicology ............................................................................................................. 38 
1.6. 
Clinical Studies of Mirvetuximab Soravtansine ....................................................... 38 
1.6.1. 
First-in-Human Phase 1 Clinical Trial: Study IMGN853-0401 ................................ 38 
1.6.2. 
Phase 3 Monotherapy Trial in Patients with Platinum-resistant EOC, 
Peritoneal, and Fallopian Tube Cancer: Study IMGN853-0403 ............................... 38 
1.6.3. 
Conclusion ............................................................................................................. 40 
1.7. 
Rationale for the Selection of Drug Dose Levels and Dosing Schedules .................. 40 
1.7.1. 
Mirvetuximab Soravtansine .................................................................................... 40 
1.7.2. 
Chemotherapeutic Agents in the Investigator’s Choice Arm ................................... 40 
1.7.2.1. 
Paclitaxel ................................................................................................................ 41 
1.7.2.2. 
Topotecan ............................................................................................................... 41 
1.7.2.3. 
Pegylated Liposomal Doxorubicin .......................................................................... 42 
1.8. 
Rationale for the Study Plan ................................................................................... 43 
1.9. 
Rationale for the Study Population .......................................................................... 43 
2. 
STUDY OBJECTIVES AND ENDPOINTS ........................................................... 44 
2.1. 
Objectives............................................................................................................... 44 
2.1.1. 
Primary Objective ................................................................................................... 44 


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2.1.2. 
Key Secondary Objectives ...................................................................................... 44 
2.1.3. 
Additional Secondary Objectives ............................................................................ 44 
2.1.4. 
Exploratory Objectives ........................................................................................... 44 
2.2. 
Endpoints ............................................................................................................... 45 
2.2.1. 
Primary Endpoint.................................................................................................... 45 
2.2.2. 
Key Secondary Endpoints ....................................................................................... 45 
2.2.3. 
Other Secondary Endpoints .................................................................................... 45 
2.2.4. 
Exploratory Endpoints ............................................................................................ 46 
3. 
STUDY POPULATION ......................................................................................... 46 
3.1. 
Criteria for Selection of Patient Population ............................................................. 46 
3.1.1. 
Inclusion Criteria .................................................................................................... 46 
3.1.2. 
Exclusion Criteria ................................................................................................... 48 
4. 
INVESTIGATIONAL PLAN ................................................................................. 49 
4.1. 
Study Design .......................................................................................................... 49 
4.1.1. 
Overview and Schema ............................................................................................ 49 
4.1.2. 
Dosing and Dosing Schedules for Mirvetuximab Soravtansine and 
Chemotherapeutic Agents ....................................................................................... 51 
5. 
STUDY TREATMENT .......................................................................................... 51 
5.1. 
Mirvetuximab Soravtansine .................................................................................... 51 
5.1.1. 
Mirvetuximab Soravtansine Packaging ................................................................... 51 
5.1.2. 
Mirvetuximab Soravtansine Accountability ............................................................ 51 
5.1.3. 
MIRV Study Treatment Compliance ....................................................................... 52 
5.2. 
Investigator’s Choice Chemotherapeutic Agents ..................................................... 52 
5.3. 
Assignment of Patient Number ............................................................................... 52 
5.3.1. 
Enrolled Patient Definition ..................................................................................... 52 
5.3.2. 
Patient Assignment to Dosing Regimens ................................................................. 53 
5.4. 
Blinding Methods ................................................................................................... 53 
5.5. 
Study Treatment Administration ............................................................................. 53 
5.5.1. 
Premedication for Study Treatment ......................................................................... 53 
5.5.1.1. 
Mirvetuximab Soravtansine .................................................................................... 53 
5.5.2. 
Prophylactic use of Corticosteroid Eye Drops ......................................................... 53 
5.5.2.2. 
IC Chemotherapy.................................................................................................... 54 


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5.5.3. 
Preparation and Administration of Mirvetuximab Soravtansine ............................... 54 
5.5.3.1. 
Calculation for Adjusted Ideal Body Weight ........................................................... 54 
5.5.3.2. 
Preparation and Administration of IC Chemotherapy .............................................. 55 
5.5.3.3. 
Preparation and Administration of Paclitaxel .......................................................... 55 
5.5.3.4. 
Preparation and Administration of Pegylated Liposomal Doxorubicin .................... 55 
5.5.3.5. 
Preparation and Administration of Topotecan ......................................................... 55 
5.6. 
Dose Modification Guidelines ................................................................................ 56 
5.6.1. 
Mirvetuximab Soravtansine .................................................................................... 56 
5.6.1.1. 
Treatment Criteria .................................................................................................. 56 
5.6.1.2. 
Mirvetuximab Soravtansine-related Adverse Events ............................................... 56 
5.6.1.3. 
Mirvetuximab Soravtansine Dose Reduction Dose Levels ...................................... 57 
5.6.1.4. 
Monitoring and Management of Nausea and Vomiting ........................................... 58 
5.6.1.5. 
Monitoring and Management of Diarrhea ............................................................... 58 
5.6.1.6. 
Ocular Disorders ..................................................................................................... 58 
5.6.1.7. 
Monitoring of Non-infectious Pneumonitis ............................................................. 61 
5.6.1.8. 
Management of Electrolytes Imbalance .................................................................. 62 
5.6.1.9. 
Potential Infusion-related Reactions ........................................................................ 63 
5.6.1.10. 
Discontinuation of Mirvetuximab Soravtansine Due to Toxicity ............................. 65 
5.6.2. 
Paclitaxel ................................................................................................................ 65 
5.6.2.1. 
Dose Reduction Dose Levels .................................................................................. 66 
5.6.2.2. 
Criteria for Permanent Discontinuation of Paclitaxel ............................................... 67 
5.6.3. 
Topotecan ............................................................................................................... 67 
5.6.3.1. 
Dose Reduction Dose Levels .................................................................................. 67 
5.6.3.2. 
Criteria for Permanent Discontinuation of Topotecan.............................................. 68 
5.6.4. 
Pegylated Liposomal Doxorubicin .......................................................................... 68 
5.6.4.1. 
Hematological Toxicities ........................................................................................ 68 
5.6.4.2. 
Non-hematological Toxicities ................................................................................. 69 
5.6.4.3. 
Criteria for Permanent Discontinuation of PLD ...................................................... 71 
5.6.4.4. 
Dose Reduction Dose Levels .................................................................................. 71 
5.7. 
Discontinuation of the Patients from the Study or Study Treatment......................... 71 
5.7.1. 
End of Treatment .................................................................................................... 71 
5.7.2. 
End of Study ........................................................................................................... 71 


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5.7.3. 
Withdrawal of Consent ........................................................................................... 71 
5.7.4. 
Lost to Follow-up ................................................................................................... 72 
5.8. 
Period of Observation ............................................................................................. 72 
5.9. 
Concomitant Medications and Procedures ............................................................... 73 
5.9.1. 
Antiemetic and Antidiarrheal Medications .............................................................. 73 
5.9.2. 
Folate-Containing Supplements .............................................................................. 73 
5.9.3. 
Antineoplastic Therapy ........................................................................................... 73 
5.9.4. 
Hematopoietic Growth Factors ............................................................................... 73 
5.9.5. 
Anticoagulants ........................................................................................................ 73 
5.9.6. 
Methods of Contraception ....................................................................................... 73 
5.9.7. 
Other Concomitant Medications ............................................................................. 74 
5.9.8. 
Medications that are CYP3A or MDR1 Substrates or CYP3A Substrates 
with Narrow Therapeutic Index .............................................................................. 75 
5.10. 
Overdose and Medication Error .............................................................................. 75 
5.10.1. 
Overdose ................................................................................................................ 75 
5.10.2. 
Medication Error .................................................................................................... 75 
6. 
PHARMACOKINETIC AND IMMUNOGENICITY ASSESSMENTS ................. 75 
6.1. 
Pharmacokinetic Assessments – Mirvetuximab Soravtansine .................................. 75 
6.2. 
Immunogenicity Assessments – Mirvetuximab Soravtansine .................................. 76 
7. 
BIOMARKER RESEARCH STUDIES .................................................................. 76 
7.1. 
Evaluation of FRα Expression in Tumor Tissue ...................................................... 76 
7.2. 
Exploratory Biomarker Studies ............................................................................... 77 
7.2.1. 
Soluble FRα............................................................................................................ 77 
7.2.2. 
Potential Predictive Markers of Drug Response ...................................................... 77 
7.2.3. 
Future Use of Biomarker Samples .......................................................................... 77 
8. 
STUDY PROCEDURES ........................................................................................ 78 
8.1. 
Informed Consent ................................................................................................... 78 
8.2. 
Inclusion and Exclusion Criteria ............................................................................. 78 
8.3. 
Confirmation of Disease Diagnosis ......................................................................... 78 
8.4. 
BRCA Mutation Status ............................................................................................ 78 
8.5. 
Demographic/Medical History ................................................................................ 79 
8.6. 
Physical Examination, Weight, and Height ............................................................. 79 


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8.7. 
Vital Signs .............................................................................................................. 79 
8.8. 
Electrocardiogram (ECG) ....................................................................................... 79 
8.9. 
Ocular Symptom Assessment and Ophthalmic Examination ................................... 79 
8.9.1. 
Ocular Symptom Assessment ................................................................................. 79 
8.9.2. 
Ophthalmic Examination ........................................................................................ 79 
8.10. 
Laboratory Assessments ......................................................................................... 80 
8.10.1. 
Clinical Laboratory Panels ...................................................................................... 80 
8.11. 
Pregnancy Screen ................................................................................................... 81 
8.12. 
Eastern Cooperative Oncology Group Performance Status ...................................... 81 
8.13. 
ECHO/MUGA Scan ............................................................................................... 81 
8.14. 
Tumor Response Assessment .................................................................................. 81 
8.14.1. 
Radiological Imaging.............................................................................................. 81 
8.14.2. 
CA-125 ................................................................................................................... 82 
8.15. 
Quality of Life Questionnaires ................................................................................ 82 
8.16. 
Health-care Resource Utilization ............................................................................ 82 
9. 
ASSESSMENT OF SAFETY ................................................................................. 83 
9.1. 
Recording Adverse Events and Serious Adverse Events.......................................... 83 
9.1.1. 
Definition of Adverse Events .................................................................................. 83 
9.1.1.1. 
Adverse Event (AE) ................................................................................................ 83 
9.1.1.2. 
Serious Adverse Event (SAE) ................................................................................. 84 
9.1.1.3. 
Adverse Events of Special Interest .......................................................................... 85 
9.1.2. 
Classification of Adverse Events ............................................................................ 85 
9.2. 
Adverse Events ....................................................................................................... 86 
9.2.1. 
Reporting Serious Adverse Events .......................................................................... 86 
9.2.1.1. 
Reporting of Disease Progression ........................................................................... 87 
9.2.2. 
Reporting a Pregnancy ............................................................................................ 87 
10. 
STUDY ACTIVITIES ............................................................................................ 88 
10.1. 
Screening Visit ....................................................................................................... 88 
10.1.1. 
Standard of Care Assessments ................................................................................ 88 
10.2. 
End of Treatment Visit ........................................................................................... 88 
10.3. 
Follow-up Assessments .......................................................................................... 89 
10.3.1. 
Safety Follow-up .................................................................................................... 89 


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10.3.2. 
Response Follow-up ............................................................................................... 89 
10.3.3. 
PFS2 and Survival Follow-up ................................................................................. 89 
11. 
STATISTICAL METHODS ................................................................................... 89 
11.1. 
Sample Size ............................................................................................................ 90 
11.2. 
Stratification ........................................................................................................... 91 
11.3. 
Pharmacokinetic Analyses ...................................................................................... 91 
11.4. 
Safety Analyses ...................................................................................................... 91 
11.5. 
Efficacy .................................................................................................................. 91 
11.5.1. 
Primary Efficacy Analysis ...................................................................................... 91 
11.5.1.1. 
Progression-Free Survival ....................................................................................... 91 
11.5.2. 
Secondary Efficacy Endpoints ................................................................................ 92 
11.5.2.1. 
Objective Response Rate ........................................................................................ 92 
11.5.2.2. 
Overall Survival ..................................................................................................... 92 
11.5.2.3. 
Patient Reported Outcomes ..................................................................................... 92 
11.6. 
Interim Analysis ..................................................................................................... 92 
11.7. 
Patient-reported Outcomes ...................................................................................... 93 
11.8. 
Multiple Comparisons ............................................................................................ 93 
11.8.1. 
Multiple Comparisons for Primary Efficacy Endpoint ............................................. 93 
11.8.2. 
Multiple Comparisons for Key Secondary Efficacy Endpoints ................................ 93 
12. 
QUALITY CONTROL AND ASSURANCE .......................................................... 94 
12.1. 
Recording of Data and Data Quality Assurance ...................................................... 94 
13. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ...................................................................................................... 94 
13.1. 
Ethical and Regulatory............................................................................................ 94 
13.1.1. 
Institutional Review Board or Independent Ethics Committee Approval ................. 94 
13.1.2. 
Patient Information and Consent ............................................................................. 95 
13.2. 
Investigators and Study Administrative Structure .................................................... 95 
13.3. 
Patient Confidentiality ............................................................................................ 96 
13.4. 
Study Monitoring.................................................................................................... 96 
13.5. 
Study Committees .................................................................................................. 97 
13.5.1. 
Steering Committee ................................................................................................ 97 
13.5.2. 
Independent Data Monitoring Committee ............................................................... 97 


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13.6. 
Case Report Forms and Study Reports .................................................................... 97 
13.7. 
Critical Documents ................................................................................................. 97 
13.8. 
Protocol Adherence ................................................................................................ 98 
13.9. 
End of Study ........................................................................................................... 98 
13.10. 
Study Termination .................................................................................................. 99 
13.11. 
Site Termination ..................................................................................................... 99 
13.12. 
Access to Source Documentation ............................................................................ 99 
13.13. 
Audits and Inspections .......................................................................................... 100 
13.14. 
Data Generation and Analysis ............................................................................... 100 
13.15. 
Retention of Data .................................................................................................. 100 
13.16. 
Financial Disclosure ............................................................................................. 100 
13.17. 
Insurance Compensation ....................................................................................... 100 
13.18. 
Publication and Disclosure Policy ......................................................................... 101 
14. 
LIST OF REFERENCES ...................................................................................... 101 
APPENDIX A. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS SCALE .................................................................... 107 
APPENDIX B. RESPONSE DEFINITIONS (RECIST 1.1) .................................................. 108 
APPENDIX C. GYNECOLOGIC CANCER INTERGROUP (GCIG) CRITERIA FOR 
EVALUATION OF CA-125 ................................................................................. 113 
APPENDIX D. LIST OF CONCOMITANT MEDICATIONS REQUIRING 
CAREFUL MONITORING .................................................................................. 116 
APPENDIX E. ADJUSTED IDEAL BODY WEIGHT (AIBW) CALCULATION ............... 117 
 
LIST OF TABLES 
Table 1: 
List of Abbreviations and Definitions of Terms ........................................................ 5 
Table 2: 
Schedule of Assessments for Arm 1 (Mirvetuximab Soravtansine): 3-Week 
Cycle ...................................................................................................................... 15 
Table 3: 
Schedule of Assessments for Arm 2 (Topotecan): 3-Week Cycle ............................ 19 
Table 4: 
Schedule of Assessments for Arm 2 (Pegylated Liposomal Doxorubicin; 
Weekly Paclitaxel; Weekly Topotecan): 4-Week Cycle .......................................... 22 
Table 5: 
Study Drug Doses and Schedules of Administration ............................................... 51 
Table 6: 
Dose Modifications for Mirvetuximab Soravtansine-related Adverse Events .......... 56 
Table 7: 
Mirvetuximab Soravtansine Dose Reduction Dose Levels ...................................... 58 


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Table 8: 
Management of Ocular Symptoms .......................................................................... 60 
Table 9: 
Management of Non-infectious Pneumonitis........................................................... 62 
Table 10: Management Guidelines for Potential Infusion-related Reactions............................ 64 
Table 11: Paclitaxel Dose Modification Guidelines ................................................................ 66 
Table 12: Paclitaxel Dose Reductions ..................................................................................... 66 
Table 13: Topotecan Dose Modification Guidelines ............................................................... 67 
Table 14: Topotecan Dose Reductions (Weekly Schedule) ..................................................... 68 
Table 15: Topotecan Dose Reductions (Five Days Schedule) ................................................. 68 
Table 16: Adverse Events Requiring Permanent Discontinuation of Topotecan ...................... 68 
Table 17: Pegylated Liposomal Doxorubicin Dose Modification Guidelines for 
Hematological Adverse Events ............................................................................... 69 
Table 18: Pegylated Liposomal Doxorubicin Dose Modification Guidelines for Hand-
foot Syndrome and Mucositis ................................................................................. 70 
Table 19: Pegylated Liposomal Doxorubicin Dose Reductions ............................................... 71 
Table 20: Pharmacokinetics Sampling Time Points ................................................................ 76 
Table 21: Clinical Laboratory Tests ........................................................................................ 80 
Table 22: Adverse Event Severity .......................................................................................... 85 
Table 23: Adverse Event Causal Relatedness ......................................................................... 86 
 
LIST OF FIGURES 
Figure 1: 
Mirvetuximab Soravtansine Structure ..................................................................... 35 
 


Mirvetuximab Soravtansine (IMGN853) 
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1. 
INTRODUCTION 
1.1. 
Target Background 
Folate receptor α (FRα) is a glycosylphosphatidylinositol-anchored cell surface protein encoded 
by the folate receptor 1 (FOLR1) gene. FRα 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, Kelemen 2006, Investigator Brochure).  
Published studies have demonstrated FRα overexpression by immunohistochemistry (IHC) in 
various epithelial tumors, particularly serous and endometrioid ovarian cancers and serous and 
endometrioid endometrial cancers (Scorer 2010, Garin-Chesa 1993, Kalli 2008, Crane 2012, 
Dainty 2007, Jones 2008, Ab 2015, and Allard 2007). IHC results obtained from patients 
screened or enrolled in the Phase 1 Study IMGN853-0401 and Phase 3 Study IMGN853-403 are 
generally consistent with the literature (Investigator Brochure). While assessing the FRα 
distribution in the PROC (platinum-resistant ovarian cancer) expansion cohort, approximately 
40% of patients had high expression.  
Several additional studies have further validated FRα as a target in serous epithelial ovarian 
cancer (EOC). First, quantitative polymerase chain reaction studies show ubiquitous FRα mRNA 
expression in serous EOC (Hanker 2012, Hoskins 1998, 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 
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 EOC 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 
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 mAb to tumor antigens with the extraordinary cytotoxicity of 
maytansine derivatives, which are potent anti-microtubule agents that target proliferating cells. 
MIRV is an ADC designed to target FRα. It consists of the humanized anti- FRα mAb M9346A 
attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4 (Figure 1). 


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Figure 1: 
Mirvetuximab Soravtansine Structure 
 
DM4 is ~2% by weight relative to mAb. 
Due to the nature of the conjugation process, the number of DM4 molecules attached to the mAb 
ranges from one to seven molecules per Ab, with an average of three or four DM4 molecules per 
Ab. Conjugation of the maytansinoid to the tumor-targeting Ab ensures that the cytotoxic 
component remains inactive in the circulation. Release of the cytotoxic payload requires binding, 
internalization, and degradation of the Ab. The released payload then kills the cell by inducing 
G2-M arrest and cell death. Cellular processing of maytansinoid conjugates can also generate 
lipophilic catabolites that cross cell membranes and kill neighboring cells (Erickson 2006).  
In vitro, MIRV binds cell surface FRα with high apparent affinity (≤ 0.1 nM) and shows potent 
(IC50 ≤ 1 nM) and selective cytotoxicity against tumor cells expressing FRα. Cytotoxic effects of 
MIRV in vitro is related to level of cell-surface expression of FRα (Ab 2015). MIRV 
additionally demonstrates significant activity against FRα positive xenografts, with partial and 
complete remissions observed in ovarian models (Ab 2015). Together with the selective 
upregulation of FRα in solid tumors, these results provide the rationale for exploring the clinical 
utility of MIRV. 
1.3. 
Epithelial Ovarian Cancer 
Ovarian cancer is a lethal disease with 22,530 new cases and 13,930 deaths expected in 2019 in 
the US (SEER Cancer Statistics Factsheet 2019). The estimated number of new EOC cases in the 
EU (EU27) in 2012 was 44,149 with 29,758 deaths (EUCAN Cancer Fact Sheet: Ovary 2019). 
The overall 5-year survival for EOC patients is only 48% (SEER Cancer Statistics Factsheet 
2019). 
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. 


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Despite considerable improvements in primary therapy, 80% of the patients with advanced EOC 
are expected to relapse during or after treatment with platinum-containing regimens 
(Armstrong 2019). Disease recurring within 6 months of platinum-based chemotherapy is 
classified as platinum resistant, whereas, disease recurring longer than 6 months after therapy is 
termed platinum sensitive. Patients with platinum-resistant disease typically receive single-agent 
chemotherapy (eg, PLD, topotecan [Topo], gemcitabine, paclitaxel [Pac], or other) at relapse. 
Unfortunately, response rates (RR) are modest (~15%) and duration of response (DOR) is 
typically 4 to 8 months (Cannistra 2010, Matsuo 2010). Similarly, overall survival (OS) is poor 
(median OS ~11 months). Bevacizumab was approved for use in combination with 
chemotherapy for recurrent EOC in the platinum-resistant setting (Pujade-Lauraine 2014). 
Because platinum-resistant EOC (PROC) remains a significant unmet medical need, the National 
Comprehensive Cancer Network (NCCN) guidelines recommend that platinum resistant patients 
participate in clinical trials (NCCN Guidelines 2019). 
Commonly used agents for PROC are Pac, Topo and PLD, all of which have modest levels of 
activity, which underscores the need for improved therapies. 
In addition to single-agent cytotoxic chemotherapy, bevacizumab combinations and poly-ADP 
ribose polymerase (PARP) inhibitors (eg, olaparib, niraparib, and rucaparib) are approved for 
treatment of previously treated EOC. These agents, however, are subject to treatment limitations. 
In particular, bevacizumab combinations are limited to patients who have received no more than 
2 prior chemotherapy regimens and are not at risk for bowel perforations (recto-sigmoid 
involvement, bowel involvement and/or history of bowel obstruction) (Aghajanian 2012, Pujade-
Lauraine 2014). Those patients with PROC who receive bevacizumab + chemotherapy typically 
receive subsequent single-agent chemotherapy if they remain eligible for further treatment. 
PARP inhibitors (eg, olaparib and rucaparib) are approved as single-agent treatment for patients 
with breast cancer susceptibility gene (BRCA) mutated EOC (~15% of EOC) and have received 
≥ 2 prior regimens (Moore 2019) based on the durable responses seen in this subset of EOC. The 
activity of PARP inhibitors in BRCA wild-type patients with PROC is negligible, with response 
rates of approximately 5% (Gelmon 2011, Moore 2019, Sandhu 2013). 
1.4. 
Current Therapies 
Current management of advanced stage disease includes surgical tumor debulking, followed by 
adjuvant platinum- and taxane-based chemotherapy. However, the majority of the patients will 
recur (Garcia 2013). Patients with relapsed platinum sensitive disease are often treated with 
carboplatin alone or as part of a combination regimen (Pfisterer 2006), whereas those with 
platinum-resistant disease may be treated with a variety of agents, including Pac, Topo and PLD.  
See Section 1.7.2 for more information on the background and doses/regimens of Pac, Topo, and 
PLD selected for this study. 


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1.5. 
Non-Clinical Studies of Mirvetuximab Soravtansine 
1.5.1. 
Correlation of FRα Expression with MIRV Activity 
Studies assessing the potency and specificity of MIRV were conducted on a panel of FRα-
positive cell lines with a wide range of FRα expression, as well as on FRα-negative cell lines. 
These studies revealed a positive correlation between the level of FRα expression on the cell 
surface, the amount of maytansinoid catabolites generated, and the degree of sensitivity of the 
cells to MIRV in vitro. MIRV is not active against low and negative FRα expressing cells. 
1.5.2. 
Pharmacology 
Results of nonclinical pharmacology studies demonstrate the following: 
• FRα has limited normal tissue expression and marked expression in solid tumors, 
particularly cancers of the ovary and endometrium (Investigator Brochure). In vitro 
studies demonstrated that MIRV binds cell surface FRα with high apparent affinity 
(≤ 0.1 nM) and shows potent (IC50 ≤ 1 nM) and selective cytotoxicity against cells 
expressing FRα. MIRV-mediated cytotoxicity involves binding, internalization, and 
degradation of MIRV, which releases DM4. DM4 can be methylated to yield S-
methyl-DM4. Both DM4 and S-methyl-DM4 can 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 MIRV express higher levels 
of FRα and release 10- to 100-fold more cytotoxic maytansinoid than cells resistant to 
MIRV.  
• MIRV retains the inherent activities of its Ab 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 Ab-
dependent cell-mediated cytotoxicity (ADCC) in vitro.  
• MIRV demonstrates significant activity against FRα -positive xenografts. Partial 
and/or complete regressions in xenograft models of EOC were seen at doses of MIRV 
well below its maximum tolerated dose (MTD).  
1.5.3. 
Pharmacokinetics 
Nonclinical studies with MIRV cross-reactive (monkey) and non-cross-reactive (mouse) species 
were conducted to define pharmacokinetics (PK) parameters and to determine the stability of the 
linker and impact of conjugation on Ab clearance. An additional PK study with free DM4 was 
conducted in monkey. PK studies demonstrated the stability of MIRV in circulation after IV 
administration, with a distribution phase lasting about 24 hours followed by a slower terminal 
elimination phase. The data indicated that the PK of MIRV were approximately dose 
proportional within the ranges evaluated (1 mg/kg – 10 mg/kg). These studies are further detailed 
in the Investigator Brochure.  


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1.5.4. 
Toxicology 
MIRV 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 FIH (FIH) study exploring 
the safety and tolerability of MIRV when administered once every three weeks to patients with 
advanced solid tumors. Potential risks suggested by these studies as well as clinical experience 
with other maytansinoid ADCs include hematologic abnormalities, electrolyte alterations, 
injection site reactions, infusion reactions, immunogenicity, hepatic abnormalities, and 
peripheral neuropathy. Toxicology studies are further detailed in the Investigator Brochure. 
1.6. 
Clinical Studies of Mirvetuximab Soravtansine 
1.6.1. 
First-in-Human Phase 1 Clinical Trial: Study IMGN853-0401 
The first-in-human (FIH) Phase 1 study evaluated the safety, PK and pharmacodynamics of 
single-agent MIRV in patients with EOC and other FRα-positive tumors. The recommended 
Phase 2 dose for single agent MIRV administered once every three weeks was determined to be 
6.0 mg/kg adjusted ideal body weight (AIBW). Data from this study, including PK and 
treatment-emergent adverse events (TEAEs) reported by patients enrolled in the dose escalation 
cohorts are detailed in the Investigator Brochure.  
The initial antitumor activity observed with MIRV monotherapy in Study IMGN853-0401, 
particularly in those patients with PROC, no more than 3 prior lines of therapy and FRα medium 
or high expression per the original “PS2+” scoring method (defined by 2+ intensity staining of 
tumor cells with medium ≥50% to <75% of tumor cells and high ≥75% of tumor cells, as 
detailed in the Investigator Brochure) suggested the potential for a significant improvement over 
single-agent chemotherapy (Pac, PLD, or Topo). Specifically, in the 36 patients with PROC, who 
had received no more than 3 prior lines of therapy, and had FRα medium or high expression, 
MIRV was associated with a confirmed Investigator-assessed ORR of 47%, median DOR of 5.8 
months, and median progression-free survival (PFS) of 6.7 months, which compared favorably 
with what would be expected with single-agent chemotherapy. Similarly, in the subset of 27 
patients with FRα-high expression, the confirmed Investigator-assessed ORR was 44%, with 
median DOR of 7.8 months and median PFS of 6.7 months. 
The initial safety profile of MIRV suggested that it was well tolerated, with a safety profile 
primarily consisting of low grade gastrointestinal (GI) adverse events (AEs) and blurred vision 
related to corneal keratopathy. The TEAEs were manageable with standard medical care and/or 
dose modification, with a low rate (10%) of patients discontinuing MIRV due to a treatment-
related TEAE.  
Safety data are further detailed in the MIRV Investigator Brochure. 
1.6.2. 
Phase 3 Monotherapy Trial in Patients with Platinum-resistant EOC, Peritoneal, 
and Fallopian Tube Cancer: Study IMGN853-0403 
IMGN853-0403 was a Phase 3 study with the objective to evaluate the safety and efficacy of 
single-agent MIRV vs. Investigator’s choice of chemotherapy (IC Chemo) in patients with 
platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer, and whose tumor 


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was FRα-positive (medium or high expression) by the Ventana IHC assay. The study was 
designed to compare the efficacy of MIRV to that of approved single-agent selected standard of 
care chemotherapy (Pac, PLD, or Topo) in patients with PROC who have received no more than 
3 prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as 
the next line of therapy. 
A total of 366 patients were randomized and assigned to the MIRV group or the IC Chemo 
groups (248 and 118, respectively) and were included in the ITT analysis. A total of 352 patients 
received at least 1 dose of MIRV or IC Chemo (243 and 109, respectively), and were included in 
the Safety population analysis. All patients in the MIRV group of the Safety population received 
a dose of 6 mg/kg AIBW every 3 weeks (Q3W). The patients in the IC Chemo group received a 
dose of single-agent chemotherapy.  
The primary endpoint was PFS by a blinded independent review committee, which was assessed 
using the Hochberg procedure in the entire study population and in the FRα-high population. The 
Hochberg procedure enables the simultaneous testing of 2 overlapping populations. Under this 
statistical analysis plan, if the p-value of the primary endpoint in either population is greater than 
0.05, the p-value in the other population needs to be less than or equal to 0.025 to achieve 
statistical significance. The primary endpoint, PFS, did not reach statistical significance in either 
the overall ITT population (p-value = 0.897; HR = 0.981) or in the pre-specified FRα-high 
population (p-value = 0.049; HR = 0.693).  
This is the first study to evaluate available chemotherapy specifically in patients with high FRα 
expression. An examination of efficacy in the FRα-high population showed clinically meaningful 
advantage for those patients randomized to MIRV vs. IC Chemo across all endpoints. MIRV 
treatment in PROC patients with high FRα expression resulted in an ORR of 24% (95% CI: 17.2, 
31.5) compared with 10% (95% CI: 4.1, 19.3) for patients randomized to IC Chemo (p-value = 
0.014), median PFS of 4.8 months (95% CI: 4.11, 5.68) vs. 3.3 months (95% CI: 1.97, 5.59) for 
patients randomized to IC Chemo (p-value = 0.049; HR = 0.693), median OS in patients 
randomized to MIRV was not reached (95% CI: 12.58, not estimable) vs. 11.8 months (95% CI: 
9.20, not estimable) for patients randomized to IC Chemotherapy (p-value = 0.033; HR = 0.618). 
OS results are not confounded by an imbalance in subsequent anti-cancer therapy. The median 
DOR using response evaluation criteria in solid tumors (RECIST) v1.1 per BIRC in the 
FRα-high population in patients randomized to MIRV was 5.7 months (95% CI: 4.17, -) vs. 4.2 
months (95% CI: 3.22, 8.71) for patients randomized to IC Chemo. Consistent with the observed 
tumor shrinkage, CA-125 responses per the Gynecologic Cancer InterGroup (GCIG) criteria 
occurred in 53% of FRα response-evaluable patients treated with MIRV (compared with 25% in 
the IC Chemotherapy group). Analysis of time to second disease progression (PFS2) suggests 
that the clinical benefit observed with MIRV does not diminish the efficacy of subsequent 
therapy (patient randomized to MIRV median 10.1 months [95% CI: 9.03, 11.20] vs. 8.4 months 
[95% CI: 7.10, 9.46] for patients randomized to IC Chemo [p-value < 0.001; HR = 0.557]). 
The efficacy and safety of MIRV from this Phase 3 study were supported by PRO data, which 
showed a larger proportion of patients with a ≥ 15 point improvement in the European 
Organization for Research and Treatment of Cancer (EORTC)-QLQ-OV28 Abdominal/GI 
symptom subscale from baseline to Week 8/9 compared to IC Chemo (32% vs 13.7% 
respectively, p=0.011). 


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For MIRV the mean half-life (t½,) was 115.1 hour (4.8 days), with little evidence of accumulation 
(mean accumulation ratio of 1.102).  
There was no apparent relationship between patients testing positive for ADA and MIRV 
exposure.  
The MIRV safety profile was predominantly characterized by low-grade nausea (51%), diarrhea 
(40%), and blurred vision (40%). These TEAEs are generally managed and mitigated with 
antiemetics, antidiarrheals, and lubricating/steroid eye drops. In the MIRV group, there were 
fewer ≥ Grade 3 TEAEs, and fewer TEAEs leading to dose reduction or delay and treatment 
discontinuation (46%, 37%, and 12%, respectively) compared with the IC Chemo group (61%, 
45%, and 19%, respectively). While myelosuppression is an important safety issue with PLD and 
Topo, MIRV is associated with less myelosuppression compared to IC Chemo, with lower rates 
of neutropenia (7% vs. 39% all grade; 0% vs. 21% Grade 3+), thrombocytopenia (11% vs. 16% 
all grade; 0% vs. 4% Grade 3+) and anemia (14% vs. 29% all grade; 2% vs. 11% Grade 3+). 
Similarly, neurotoxicity is an important safety issue with Pac; MIRV, an ADC with the tubulin-
directed payload DM4, is associated with less peripheral neuropathy than Pac (15% vs. 28% 
Grade 2+) and less alopecia (3% vs. 22% all grades). The safety profile of MIRV in the high 
FRα subset is consistent with that observed in the overall MIRV safety population. 
Please see the Investigator Brochure for information on Study IMGN853-0403.  
1.6.3. 
Conclusion 
The available safety and efficacy data from the 455 patients treated with single-agent MIRV in 
previous clinical studies are consistent with a positive risk benefit assessment. The potential 
benefit of the anti-tumor activity demonstrated by MIRV in patients with FRα high platinum 
resistant ovarian cancer, a population with high unmet need, outweighs the risks associated with 
the well tolerated safety profile, as summarized above. 
1.7. 
Rationale for the Selection of Drug Dose Levels and Dosing 
Schedules 
1.7.1. 
Mirvetuximab Soravtansine 
The selection of the Phase 3 dose of 6 mg/kg AIBW IV Q3W was based on data obtained from 
Study IMGN853-0401, a FIH study designed to establish the MTD and determine the 
recommended phase 2 dose (RP2D) of MIRV when administered IV as a single agent in adult 
patients with FRα-positive solid tumors who have relapsed or are refractory to standard 
therapies. The appropriateness of this dose and regimen in patients with PROC was further 
supported by the results of the Phase 3 study IMGN853-0403. For more information please see 
the Investigator Brochure.  
1.7.2. 
Chemotherapeutic Agents in the Investigator’s Choice Arm 
The three drugs most commonly used in the setting of platinum resistance are PLD, Pac and 
Topo (Ledermann 2013 [ESMO Guidelines], NCCN Guidelines 2019 and Luvero 2014). The 
ability of patients to tolerate the bone marrow suppressive effects of cytotoxic chemotherapy is 


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less than that of patients receiving initial therapy. Modified doses and administration schedules 
(outside of the label for first line or second-line EOC) are therefore, typically used to treat EOC 
in such settings.  
1.7.2.1. 
Paclitaxel 
Pac is a taxane that can stabilize microtubules to inhibit cell division. The drug was approved for 
treatment of recurrent EOC when response rates (RR) of 25% to 37% were observed in multiple 
Phase 2 trials testing the 3-weekly schedule (McGuire 1989, Thigpen 1994, Rowinsky 1995). In 
the study by Thigpen et al, a median PFS of 4.2 months and an OS of 16 months were observed. 
A Phase 2 trial showed that weekly dosing could lead to a 20.9% ORR in platinum- and Pac-
resistant EOC patients (Gynecologic Oncology Group 2006). This alternative weekly dosing 
schedule for Pac was studied in many trials in refractory, persistent, or recurrent EOC patients, as 
reviewed by Baird et al (Baird 2010). A randomized Phase 3 study comparing weekly vs. 
3-weekly Pac in recurrent EOC patients (of whom half were platinum-resistant) showed no 
difference in RR, PFS, or OS. However, the weekly schedule had a better safety profile than the 
3-weekly schedule, as considerably less neutropenia, neuropathy, and myalgia were observed 
(Rustin 2004). Of note, the occurrence of neutropenia was also reduced when Pac was infused 
over 3 hours instead of 24 hours (Eisenhauer 1994). A recent randomized Phase 2 clinical trial 
(CARTAXHY) tested the efficacy of weekly Pac as a single agent, or in combination with 
carboplatin, or weekly Topo in patients with PROC. The results showed that the combination 
treatments increased hypersensitivity reactions, febrile neutropenia, and anemia, and did not 
improve ORR or median PFS when compared to single agent weekly Pac (Lortholary 2012). 
The approved schedule of Pac Q3W for second-line treatment of EOC is associated with a high 
rate of myelosuppression, particularly neutropenia, and peripheral neuropathy. Investigators 
therefore developed interest in evaluating the antitumor activity and tolerability of Pac 
administered on a weekly schedule, exploring it in several Phase 2 studies (Rustin 2004, 
Markman 2002). The weekly schedule is associated with similar efficacy and an improved 
toxicity profile, with less bone marrow suppression and neuropathy, as summarized by Baird et 
al (Baird 2010). Toxicities are managed with dose reductions and/or holding the D22 dosing on 
the weekly schedule. In the Phase 3 AURELIA study, the weekly Pac regimen resulted in an 
ORR of 30.2% in patients with PROC with 1 to 2 prior lines of therapy (Poveda 2015).  
1.7.2.2. 
Topotecan 
Topo’s mechanism of action is different from that of Pac, as it does not directly block cell 
division, but instead induces irreversible DNA damage. Topo inhibits topoisomerase 1, leading 
to both single and double stranded DNA breaks that eventually promote apoptosis. Topo 
(administered QD 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 Pac, with ORR of 21% vs. 13%, and median PFS of 23 
weeks vs. 14 weeks, respectively (ten Bokkel Huinink 1997). Unfortunately, Topo 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). 


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As such toxicities are often dose limiting, multiple clinical trials have studied alternative dosing 
schedules to improve the tolerability of Topo treatment (Armstrong 2019, Armstrong 2004, 
Hoskins 1998, Markman 2000). For example, one Phase 2 trial tested the effect of the “standard” 
dosing of Topo (1.5 mg/m2, daily the first 5 days of 21-day cycles) compared with an alternative 
dosing regimen (1.75 mg/m2, QW for 4 weeks, repeated every six weeks) in patients with 
recurrent EOC. The alternative dosing regimen led to a lower ORR (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 the 
first three days of 21-day cycles) (Markman 2000). Compared to historical controls, this 
alternative dosing regimen seemed to decrease the toxicity of Topo (Armstrong 2004). In a meta-
analysis of various clinical trials, it was concluded that modification of the Topo dose, and 
potentially the dosing schedule, can indeed reduce hematologic toxicity without decreasing the 
efficacy of the drug (Armstrong 2019). 
The approved Topo dosing for relapsed EOC is 1.5 mg/ m2/d, administered on days 1 to 5 of a 3-
week schedule. However, reduced doses (ie, 1.25 mg/m2/d) are associated with decreased 
toxicity and similar outcome, thereby being widely used in routine clinical practice 
(Sehouli 2009). Results from several studies suggest that women with relapsed EOC may benefit 
from similar effectiveness but significantly lower hematologic toxicity if Topo is administered in 
a weekly schedule. A Phase 2 trial of the North-Eastern German Society of Gynaecology 
Oncology Ovarian Cancer Study Group, has compared weekly schedule vs. the conventional 5-
day schedule, reporting comparable OS rates and a favorable toxicity profile for weekly 
4.0 mg/m2/week Topo, making it another viable option in PROC (Sehouli 2011). Based on this 
evidence from the literature, a conventional (1.25 mg/m2/d, on days 1 to 5 of a 3-week schedule) 
and an alternative (4.0 mg/m2/week, days 1, 8, and 15 of a 4 week cycle) schedules of Topo were 
selected for the study. 
1.7.2.3. 
Pegylated Liposomal Doxorubicin 
PLD is approved as monotherapy in recurrent PROC. The approved dose and schedule of 
50 mg/m2 every 28-days of PLD results in a substantial incidence (approximately 20%–30%) of 
Grade 3 “hand-foot-syndrome” (Markman 2011). Considerable clinical experience generated 
since the initial regulatory approval of PLD has revealed equivalent clinical activity with 
substantially less severe adverse events when this agent is administered at a dose of 40 mg/m2 
(rather than 50 mg/m2) on a 4-week schedule (Markman 2011). Results of two randomized Phase 
2 trials (Markman 2000, Wilailak 2004) provide strong support for the conclusion that the 
40 mg/m2 dose level of PLD is therapeutically equivalent to the higher (and more toxic) dose 
approved for standard use in the second-line management of EOC. Recently a study was 
conducted to show equivalence in efficacy of PLD 40 mg/m2 and PLD 50 mg/m2 
(Yoshizawa 2015). This randomized controlled study also supports the use of an initial dose of 
40 mg/m2 PLD.  
PLD is another standard chemotherapy regimen used for treating PROC. The active component 
of this drug (doxorubicin) is an anthracycline that intercalates DNA, leading to inhibition of 
replication and, subsequently, the inhibition of proper cell division. Efficacy of PLD in PROC 


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EOC has been confirmed in several Phase 2 trials. In detail, the trial by Muggia et al reported a 
26% RR, median PFS of 5.7 months, and OS of 11 months (Muggia 1997). A subsequent trial 
showed a 17% ORR and median PFS of 4.5 months (Gelmon 2011). Of note, a Phase 3 trial 
testing Topo treatment vs. PLD treatment showed a trend toward a higher ORR in the PROC 
patients subset treated with PLD, although there was no improvement of PFS or OS 
(Gordon 2001, Gordon 2004). 
1.8. 
Rationale for the Study Plan 
The design of this study is based on data obtained from Phase 3 study (IMGN853-0403), which 
showed a potential for a clinically meaningful advantage for MIRV over IC Chemo (the same 
therapies selected for this study) in patients with high FRα expression. While that prior study did 
not reach statistical significance in the entire population (patients with medium and high FRα), 
those patients with high FRα expression showed promising results.  
This Phase 3, open-label, randomized study is designed to compare the efficacy of MIRV to 
selected standard IC Chemo in patients with platinum-resistant high-grade EOC, primary 
peritoneal, or fallopian tube cancer, whose tumors express a high level of FRα. 
This study will compare the safety and efficacy of MIRV administered at 6 mg/kg AIBW Q3W 
with IC Chemo (Pac, PLD or Topo). Patients will be enrolled 1:1 into one of two arms as 
follows:  
• Arm 1: MIRV 6 mg/kg AIBW Q3W 
• Arm 2: IC Chemo  
1.9. 
Rationale for the Study Population 
The study population included in this study was initially based on clinical observations from a 
Phase 1 study of MIRV (Study IMGN853-0401), which showed promising clinical activity in 
patients with PROC. Results from that study suggested that higher FRα levels correlated with 
response to treatment (Martin 2015). Based on those results, a large, randomized Phase 3 study 
in patients with platinum-resistant advanced high-grade EOC, primary peritoneal, or fallopian 
tube cancers was initiated. Eligible patients were required to have tumors expressing what was 
considered a medium or high level FRα expression per the Ventana IHC assay using a newly 
implemented “10x” scoring method. Results from this study showed that while the study did not 
meet the primary endpoint per Hochberg procedure, MIRV showed consistently favorable 
efficacy when compared to IC Chemo in measures of PFS, ORR, OS, DOR, PFS2, CA-125, and 
PRO endpoints in patients high FRα expression. Subsequent review demonstrated that the “10x” 
scoring method for the FOLR1 IHC assay misclassified a significant percentage of patients, and 
thus further impacted the study results. Ad hoc analyses of the PS2+ high FRα patients revealed 
enhanced benefit from MIRV for ORR, PFS and OS compared to IC Chemo controls. These 
findings warranted a follow-up study focusing solely on patients with high FRα expression using 
the original “PS2+” scoring method. Thus, the present study will enroll a similar PROC 
population to the prior Phase 3 study, with the exception that patients are required to have high 
FRα expression by PS2+ scoring as determined by the Ventana FOLR1 (FOLR-2.1) CDx assay. 


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Please refer to the Investigator Brochure for more details on the Ventana FOLR1 assay and the 
FRα expression threshold selected for this study. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
2.1.1. 
Primary Objective 
• To compare the PFS of patients randomized to MIRV vs. IC Chemo  
2.1.2. 
Key Secondary Objectives 
• To compare the ORR of patients randomized to MIRV vs. IC Chemo 
• To compare OS of patients randomized to MIRV vs. IC Chemo  
• To compare the primary patient-reported outcome (PRO) using the EORTC QLQ-
OV28 (abdominal/GI symptom scale) assessment from patients randomized to MIRV 
vs. IC Chemo 
2.1.3. 
Additional Secondary Objectives 
• To compare the safety and tolerability of MIRV vs. IC Chemo  
• To compare the DOR in patients randomized to MIRV vs. IC Chemo 
• To compare the CA-125 RR per GCIG CA-125 criteria in patients randomized to 
MIRV vs. IC Chemo  
• To compare the time to progression or death on the next line of treatment (PFS2) in 
patients randomized to MIRV vs. IC Chemo  
2.1.4. 
Exploratory Objectives 
• To assess PRO using the EORTC QLQ-C30, EQ-5D-5L, and Patient Global 
Impression of Severity (PGIS) questionnaires 
• To evaluate concentrations of MIRV, TAb, DM4 and S-methyl DM4, using sparse 
sampling 
• To assess the immunogenicity of MIRV via anti-drug antibodies (ADAs)  
• To evaluate potential biomarkers in blood and tumor tissue predictive of response to 
MIRV 


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2.2. 
Endpoints 
2.2.1. 
Primary Endpoint 
• PFS, defined as the time from date of randomization until Investigator-assessed 
progressive disease (PD) or death, whichever occurs first. Results will be summarized 
by arm  
− Kaplan-Meier method for survival function estimate 
− Stratified Cox proportional hazard regression for hazard ratio (HR) estimate 
− Stratified log-rank test for hypothesis testing 
2.2.2. 
Key Secondary Endpoints 
• Objective response includes best response of complete response (CR) or partial 
response (PR) as assessed by the Investigator 
− Stratified Cochran-Mantel-Haenszel (CMH) test for treatment comparison 
− Clopper-Pearson method for 95% CI estimation 
• OS defined as the time from date of randomization until the date of death. Patients 
alive at the time of analysis will be censored at the last known date known to be alive  
− Kaplan-Meier method for survival function estimate 
− Stratified Cox proportional hazard regression for HR estimate 
− Stratified log-rank test for hypothesis testing 
• Primary PRO assessment, defined as the number of patients achieving at least 
15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of 
EORTC QLQ-OV28 
2.2.3. 
Other Secondary Endpoints 
• DOR defined as the time from initial response until Investigator-assessed PD for all 
patients who achieve a confirmed objective response (PR or CR) 
− Kaplan-Meier method for survival function estimate 
− Unstratified Cox proportional hazard regression for HR estimate 
− Unstratified log-rank test for hypothesis testing 
• CA-125 response determined using the GCIG criteria defined in Section 8.14.2.  
CA-125 response per GCIG criteria will be determined programmatically  
• PFS2 defined as the time from date of randomization until second disease progression 
or death whichever occurs first. Results will be summarized by arm  
• TEAEs, laboratory test results, physical examination findings, and vital signs 


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2.2.4. 
Exploratory Endpoints 
Exploratory endpoints are provided below. The analysis and subsequent results of these 
assessments may be reported in separate documents and not included in the Statistical Analysis 
Plan or Clinical Study Report, respectively. 
• EORTC QLQ-C30/OV-28, EQ5D-5L, and PGIS 
• PK parameters will not be calculated due to the use of a sparse sampling schedule. 
Summary statistics of intact ADC, total Ab, DM4 and S-methyl DM4 concentration 
data by time will be presented 
• Immunogenicity is defined as the presence of ADA to MIRV. Based on 
seroconversion status, the impact of ADA on both efficacy and safety will be 
evaluated 
• Identification of soluble FRα levels and other biomarkers, such as protein, genetic, 
and/or gene expression changes, related to solid malignancies and/or MIRV or IC 
Chemo mechanism of action. Patient samples will only be used for exploratory 
research related to this trial and the development of MIRV 
3. 
STUDY POPULATION 
3.1. 
Criteria for Selection of Patient Population 
3.1.1. 
Inclusion Criteria 
1. Female patients ≥ 18 years of age 
2. Patients must have a confirmed diagnosis of high-grade serous EOC, primary peritoneal 
cancer, or fallopian tube cancer  
3. Patients must have platinum-resistant disease:  
a. Patients who have only had 1 line of platinum based therapy must have received 
at least 4 cycles of platinum, must have had a response (CR or PR) and then 
progressed between > 3 months and ≤ 6 months after the date last dose of 
platinum 
b. Patients who have received 2 or 3 lines of platinum therapy must have progressed 
on or within 6 months after the date of the last dose of platinum  
Note: Progression should be calculated from the date of the last administered dose 
of platinum therapy to the date of the radiographic imaging showing progression  
Note: Patients who are platinum-refractory during front-line treatment are excluded (see 
exclusion criteria) 
4. Patients must have progressed radiographically on or after their most recent line of 
therapy 
 


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5. Patients must be willing to provide an archival tumor tissue block or slides, or undergo 
procedure to obtain a new biopsy using a low risk, medically routine procedure for 
immunohistochemistry (IHC) confirmation of FRα positivity  
6. Patient’s tumor must be positive for FRα expression as defined by the Ventana FOLR1 
(FOLR-2.1) CDx assay 
7. Patients must have at least one lesion that meets the definition of measurable disease by 
RECIST v1.1 (radiologically measured by the Investigator) 
8. Patients must have received at least 1 but no more than 3 prior systemic lines of 
anticancer therapy, and for whom single-agent therapy is appropriate as the next line of 
treatment: 
a. Adjuvant ± neoadjuvant considered one line of therapy 
b. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part 
of the preceding line of therapy (ie, not counted independently) 
c. Therapy changed due to toxicity in the absence of progression will be considered as 
part of the same line (ie, not counted independently) 
d. Hormonal therapy will be counted as a separate line of therapy unless it was given as 
maintenance 
9. Patient must have an Eastern Cooperative Oncology Group Performance Status 
(ECOG PS) of 0 or 1 
10. Time from prior therapy: 
a. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter) 
b. Focal radiation completed at least 2 weeks prior to first dose of study drug 
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-
related toxicities 
12. Major surgery must be completed at least 4 weeks prior to first dose and have recovered 
or stabilized from the side effects of prior surgery 
13. Patients must have adequate hematologic, liver, and kidney functions defined as: 
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL) without G-CSF in the 
prior 10 days or long-acting WBC growth factors in the prior 20 days 
b. Platelet count ≥ 100 x 109/L (100,000/μL) without platelet transfusion in the prior 
10 days 
c. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 
21 days 
d. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) 
e. AST and ALT ≤ 3.0 x ULN  
f. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert 
syndrome are eligible if total bilirubin < 3.0 x ULN 
g. Serum albumin ≥ 2 g/dL 
14. Patients or their legally authorized representative must be willing and able to sign the 
informed consent form (ICF) and to adhere to the protocol requirements 


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15. Women of childbearing potential (WCBP) must agree to use highly effective 
contraceptive method(s) (as defined in Section 5.9.6) while on study drug and for at least 
3 months after the last dose of MIRV or at least 6 months after the last dose of Pac, PLD, 
or Topo 
16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of study 
drug 
3.1.2. 
Exclusion Criteria  
1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors 
containing any of the above histologies, or low-grade or borderline ovarian tumor 
2. Patients with primary platinum-refractory disease, defined as disease that did not respond 
to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-
containing chemotherapy 
3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone 
marrow 
4. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0 
5. Patients with active or chronic corneal disorders, history of corneal transplantation, or 
active ocular conditions requiring ongoing treatment/monitoring such as uncontrolled 
glaucoma, wet age-related macular degeneration requiring intravitreal injections, active 
diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, 
and /or monocular vision 
6. Patients with serious concurrent illness or clinically relevant active infection, including, 
but not limited to the following: 
a. Active hepatitis B or C infection (whether or not on active antiviral therapy)  
b. HIV infection 
c. Active cytomegalovirus infection  
d. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks 
before starting study drug 
Note: Testing at screening is not required for the above infections unless clinically 
indicated 
7. Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-
Eaton syndrome (paraneoplastic syndrome) 
8. Patients with clinically significant cardiac disease including, but not limited to, any one 
of the following: 
a. Myocardial infarction ≤ 6 months prior to first dose 
b. Unstable angina pectoris 
c. Uncontrolled congestive heart failure (New York Heart Association > class II) 
d. Uncontrolled ≥ Grade 3 hypertension (per CTCAE) 
e. Uncontrolled cardiac arrhythmias 


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9. Patients assigned to PLD stratum only:  
• Left ventricular ejection fraction (LVEF) below the institutional limit of normal as 
measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan  
10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to 
randomization 
11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 
12. Patients with a previous clinical diagnosis of non-infectious interstitial lung disease 
(ILD), including noninfectious pneumonitis 
13. Patients with required use of folate-containing supplements (eg, folate deficiency) 
14. Patients with prior hypersensitivity to monoclonal antibodies 
15. Women who are pregnant or lactating 
16. Patients with prior treatment with MIRV or other FRα-targeting agents 
17. Patients with untreated or symptomatic central nervous system (CNS) metastases 
18. Patients with a history of other malignancy within 3 years prior to randomization  
Note: does not include tumors with a negligible risk for metastasis or death (eg, 
adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or 
carcinoma in situ of the cervix or breast 
19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients 
20. People who are detained through a court or administrative decision, receiving psychiatric 
care against their will, adults who are the subject of a legal protection order (under 
tutorship/curatorship), people who are unable to express their consent, and people who 
are subject to a legal guardianship order 
21. Simultaneous participation in another research study, in countries or localities where this 
is the health authority guidance 
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 Phase 3 study is designed to compare the efficacy and safety of MIRV vs. IC Chemo in 
patients with platinum-resistant high-grade EOC, primary peritoneal, or fallopian tube cancer, 
whose tumors express a high level of FRα. Patients will be, in the opinion of the Investigator, 
appropriate for single-agent therapy. FRα expression will be defined by the Ventana FOLR1 
(FOLR1-2.1) CDx assay. 


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This study will be opened/active at approximately 200 sites globally. Eligible patients (N = 430), 
who have provided informed consent and meet study entry criteria will be randomized (1:1) to 
one of two arms:  
• Arm 1 (n = 215): MIRV 6 mg/kg AIBW Q3W  
• Arm 2 (n = 215): IC Chemo, at one of the following regimens as determined by the 
Investigator prior to randomization:  
− Paclitaxel (Pac; 80 mg/m2) administered QW  
− Pegylated liposomal doxorubicin (PLD; 40 mg/m2) administered Q4W  
− Topotecan (Topo; 4 mg/m2) administered either on Days 1, 8, and 15 every 
4 weeks (Q4W) or for 5 consecutive days (1.25 mg/m2 Days 1–5) Q3W 
Patients will be stratified by the following variable at baseline: 
• Number of prior lines of therapy (1 vs. 2 vs. 3) 
• IC Chemo (Pac vs. PLD vs. Topo) chosen prior to randomization  
Disease progression will be evaluated by the Investigator using RECIST v 1.1 (Appendix B). CT 
or magnetic resonance imaging (MRI) scans will be collected and held for sensitivity analysis by 
a BICR. 
Patients will continue to receive study drug until disease progression, unacceptable toxicity, 
withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first).  
Tumor assessments, including radiological assessments by CT/MRI scans will be performed at 
Screening and subsequently every 6 weeks (± 1 week) from C1D1 (for all regimens) for the first 
36 weeks then every 12 weeks (± 3 weeks) until disease progression, death, the initiation of 
subsequent anticancer therapy, or patient’s withdrawal of consent, whichever occurs first.  
Patients who discontinue study treatment for reasons other than progressive disease (PD) will 
continue with tumor assessments until documentation of PD or the start of a new anticancer 
therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments should 
occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of 
no more than 12 weeks. After Week 36, assessment will occur every 12 weeks (± 3 weeks) until 
documentation of PD, death, the start of new anticancer therapy or patient’s withdrawal of 
consent (whichever comes first). 
All patients who discontinue study drug will be followed every 3 months (±1 month) until death, 
lost to follow-up, withdrawal of consent for survival follow-up, or end of study (EOS), 
whichever comes first. All patients will be followed for PFS2 and survival until 300 deaths have 
occurred.  
Two interim analyses will be conducted, (1) an interim futility analysis (PFS only) when at least 
110 PFS events have occurred, and (2) an interim analysis for OS at the time of final analysis of 
PFS when at least 330 PFS events have occurred. The final analysis for OS will be conducted 
when at least 300 deaths have occurred. 


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4.1.2. 
Dosing and Dosing Schedules for Mirvetuximab Soravtansine and 
Chemotherapeutic Agents 
The dose and schedule of study treatment are outlined in Table 5.  
The dose of chemotherapeutic agents will be calculated using body surface area (BSA). 
Institutional conventions may be used to calculate BSA. 
Table 5: 
Study Drug Doses and Schedules of Administration 
Group 
Drug 
Dose 
Dosing Schedule 
Arm 1 
MIRV 
6 mg/kg AIBW IV 
Day 1 of a 3-week cycle  
Arm 2 
Pac 
80 mg/m2 IV 
Days 1, 8, 15, and 22 of a 4-week cycle 
 
PLD 
40 mg/m2 IV 
Day 1 of a 4-week cycle 
Topo  
4 mg/m2 IV 
Days 1, 8, and 15 of a 4-week cycle 
Topo  
1.25 mg/m2 IV 
Days 1 to 5 of a 3-week cycle  
Abbreviations: MIRV = mirvetuximab soravtansine; Pac = paclitaxel; PLD = pegylated liposomal doxorubicin; 
Topo = topotecan; AIBW = adjusted ideal body weight. 
5. 
STUDY TREATMENT 
5.1. 
Mirvetuximab Soravtansine 
The investigational study drug, MIRV, will be provided by ImmunoGen, at a protein 
concentration of 5.0 mg/mL in an aqueous pH 5.0 buffered solution. See the Investigator 
Brochure for complete list of excipients. 
5.1.1. 
Mirvetuximab Soravtansine Packaging 
MIRV will be provided in a 20 mL glass, single-use Type I vial. The container closure for the 
Type I glass vials will consist of a 20 mm ETFE-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 labeling information. 
5.1.2. 
Mirvetuximab Soravtansine Accountability 
Specific details regarding storage and handling of MIRV can be found in the Pharmacy Manual. 
Accountability and shipping documents for MIRV must be maintained by the Principal 
Investigator (PI) or designee (eg, the study pharmacist, contract research organization 
representative, or auditor). The Investigator or designee must maintain an accurate record of all 
MIRV received, stored, dispensed, destroyed, and used in an Investigational Product 
Dispensing/Accountability Log or equivalent. These records must always be available for 
inspection, and a copy will be supplied to ImmunoGen on request. Information recorded on the 
Accountability Log will include dates and quantities of drug received, dates and quantities of 
drug dispensed, patient number and initials to whom drug is administered, lot number of drug 
administered, the recorder’s initials, and dates and quantities of drug destroyed or returned. Upon 


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receipt, vials should be visually inspected for vial integrity (ie, cracks or leaks) and a record of 
any damaged or suspect drug should be kept on the Accountability Log. 
Upon completion of the study, all MIRV dispatched to a site must be accounted for and unused 
supplies destroyed according to the site’s Standard Operating Procedures (SOPs) or returned to 
depot (refer to Pharmacy Manual). The original drug reconciliation records shall be maintained 
at the site and a copy collected and sent to ImmunoGen or designee once a representative of the 
company has confirmed the drug accountability. The clinical trial database shall also record 
details of MIRV administration such as date and time of administration. 
Drug accountability will be monitored. 
5.1.3. 
MIRV Study Treatment Compliance 
The MIRV supplied for the study may not be used for any purpose other than the study or 
administered other than as described in this protocol.  
If necessary, MIRV from different drug lots may 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 Food and Drug Administration (FDA) Form 1572 or equivalent form, 
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 PI (ie, hospital 
pharmacy, satellite pharmacy), it is the responsibility of the PI to ensure that all study drug is 
stored and administered as described (refer to Pharmacy Manual for instructions). 
5.2. 
Investigator’s Choice Chemotherapeutic Agents 
Since the type of IC Chemo received is one of the stratification factors, it is required that the 
choice of the chemotherapy agent, Pac or PLD or Topo, be made prior to randomization. Pac, 
PLD and Topo are supplied as commercially available formulations. Refer to the prescribing 
information or SmPC for complete information.  
A separate Investigational Product Dispensing/Accountability Log or equivalent must be 
maintained for Pac, PLD, and Topo. Vials should be visually inspected for vial integrity (ie, 
cracks or leaks) and a record of any damaged or suspect drug should be kept on the 
Investigational Product Dispensing/Accountability Log or equivalent. 
5.3. 
Assignment of Patient Number 
Patient numbers are assigned in sequential order as patients sign the pre-screening informed 
consent 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 prior to dosing.  
5.3.1. 
Enrolled Patient Definition 
Patients who have consented to the study and randomized, are considered enrolled. Patients who 
are issued a patient number, but who do not successfully complete the screening process and are 


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not randomized will be considered screen failures. Patient numbers for patients who screen fail 
will not be re-issued. 
5.3.2. 
Patient Assignment to Dosing Regimens 
Eligible patients will be randomly assigned 1:1 to MIRV 6 mg/kg AIBW Q3W (Arm 1) or IC 
Chemo (Arm 2; Pac, PLD or Topo).  
Cycle 1 Day 1 must occur within seven calendar days from randomization.  
Patients will be stratified as follows:  
• Number of prior therapies (1 vs. 2 vs. 3) 
• IC of chemotherapy (Pac, PLD, or Topo) 
5.4. 
Blinding Methods 
Not applicable as this is an open-label study. A Data Access Plan will describe procedures to 
restrict access to efficacy data for certain team members. 
5.5. 
Study Treatment Administration 
5.5.1. 
Premedication for Study Treatment 
5.5.1.1. 
Mirvetuximab Soravtansine 
All patients receiving MIRV must receive 325-650 mg of acetaminophen/paracetamol (PO or 
IV), 10 mg IV dexamethasone, and 25-50 mg diphenhydramine (IV or PO) (equivalent drugs of 
similar drug classes is also acceptable) approximately 30 min before each infusion of MIRV. If 
individual patients require more intensive treatment to prevent infusion-related reactions (IRRs), 
investigators may modify the regimen accordingly. An antiemetic medication (eg, 5-HT3 
serotonin receptor antagonists such as palonosetron, granisetron or ondansetron or appropriate 
alternatives) is recommended before each MIRV dose and may be used any time at the discretion 
of the treating physician. 
5.5.2. 
Prophylactic use of Corticosteroid Eye Drops 
Patients receiving MIRV will be mandated to use corticosteroid eye drops as prescribed by the 
treating physician unless the risk outweighs the benefit as per the ophthalmologist/physician. All 
patients receiving MIRV will be instructed to self-administer 1% prednisolone (Pred Forte® or 
generic equivalent) 6 times daily on Days -1 to 4 and QID on Days 5 to 8 of each cycle during 
the study. 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 to 8 of each cycle at a frequency prescribed by the 
ophthalmologist. Given the lack of availability in some regions, if prednisolone eye drops cannot 
be obtained, alternate steroid eye drops are acceptable. 


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5.5.2.1.1. Lubricating Artificial Tears 
Patients receiving MIRV will be mandated to use lubricating artificial tears on a daily basis (as 
directed by the product label or the treating physician). Preservative-free lubricating drops are 
recommended. Patients should be advised to wait at least 15 minutes after corticosteroid eye 
drop administration before instilling lubricating eye drops.  
5.5.2.2. 
IC Chemotherapy 
Patients receiving Pac, PLD or Topo may receive premedication at the discretion of the 
Investigator or according to institutional guidelines. 
5.5.3. 
Preparation and Administration of Mirvetuximab Soravtansine 
5.5.3.1. 
Calculation for Adjusted Ideal Body Weight 
The total dose of drug is calculated based on each patient’s AIBW using the following formula 
(Appendix E): 
Adjusted Ideal Body Weight (AIBW) 
AIBW = IBW1 + 0.4 (Actual weight – IBW1) 
Where: 
Ideal Body Weight (IBW) 
IBW1 (female) = 0.9H1-92 
(1H=height in cm; W=weight in kg) 
The weight used for calculation should be obtained before study drug administration on C1D1 
(-14 days) and thereafter should only be modified for significant (≥ 10%) changes in body 
weight (not influenced by weight gain or loss attributed to fluid retention).  
5.5.3.1.1. Preparation 
MIRV is an experimental anticancer 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. The desired amount of drug should be 
withdrawn from the vial(s) and diluted using 5% dextrose to a final concentration as outlined in 
the Pharmacy Manual.  
Note: MIRV is incompatible with saline (0.9% sodium chloride). Therefore, dilutions 
should be made using 5% dextrose. Infusion bags must be labeled with the protocol number, 
patient number, storage temperature, dose, and volume of MIRV filtered into the bag, or labeled 
according to institutional protocol. Once the solution is prepared, the infusion bag should be 
stored at room temperature protected from direct sunlight, and the infusion must be completed 
within eight hours of preparation. Please refer to Pharmacy Manual for further details. 
If necessary study drug from different drug lots may be mixed in a single-dose administration. 


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5.5.3.1.2. Administration 
MIRV is administered at 6 mg/kg as an IV infusion following preparation as outlined in the 
Pharmacy Manual. Details on required and compatible infusion materials are also included in the 
Pharmacy Manual.  
At C1D1 MIRV study drug should be administered at a rate of 1 mg/min; after 30 min, the rate 
can be increased to 3 mg/min if well tolerated. If well tolerated after 30 min at 3 mg/min, the 
MIRV infusion rate may be increased to 5 mg/min. Subsequent infusions may be delivered at the 
tolerated rate. 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 prn to ensure delivery 
of the full dose.  
Patients are carefully observed during each infusion and vital signs are taken as outlined in the 
Schedule of Assessments (Table 2, Table 3, and Table 4). Patients will remain in the clinic under 
observation for four hours after the first infusion, and for at least one hour after each subsequent 
infusion. While in the treatment area, patients are closely monitored for AEs. 
5.5.3.2. 
Preparation and Administration of IC Chemotherapy 
Precautions should be taken when handling Pac, PLD, and Topo. Refer to the Pharmacy Manual 
and package inserts for more information. 
5.5.3.3. 
Preparation and Administration of Paclitaxel 
Pac will be administered at 80 mg/m2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-
week cycle. Pac will be prepared as described in the prescribing information and administered IV 
at 80 mg/m2. Body weight at C1D1 (-14 days) is to be used to calculate BSA to determine the 
required dose. No dose modifications are foreseen unless the patient’s body weight changes by 
±10% from baseline. 
5.5.3.4. 
Preparation and Administration of Pegylated Liposomal Doxorubicin 
PLD will be prepared as described in the prescribing information and administered at 40 mg/m2 
as a 1 mg/min IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, PLD can be 
delivered as a 1-hour IV infusion. Body weight at C1D1 (-14 days) is to be used to calculate 
BSA to determine the required dose. No dose modifications are foreseen unless the patient’s 
body weight changes by ± 10% from baseline. 
5.5.3.5. 
Preparation and Administration of Topotecan 
Topo will be prepared as described in the prescribing information and administered at 4 mg/m2 
as a 30-min IV infusion on Days 1, 8 and 15 of a 4-week cycle. Alternatively, Topo may also be 
administered at 1.25 mg/m2 as a 30-min IV infusion on Days 1 to 5 of a 3-week cycle. Body 
weight at C1D1 (-14 days) is to be used to calculate BSA to determine the required dose. No 
dose modifications are foreseen unless the patient’s body weight changes by ± 10% from 
baseline. 


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5.6. 
Dose Modification Guidelines 
Detailed MIRV and chemotherapy-specific dose modification guidelines are described below.  
5.6.1. 
Mirvetuximab Soravtansine 
5.6.1.1. 
Treatment Criteria 
In the absence of a TEAE that requires dose modification (as specified in the management 
guidance for a particular toxicity, see Section 5.6.1.2), a patient must meet the following criteria 
to receive study drug at any cycle: 
• ANC must be ≥ 1.5 x 109/L (1,500/µL) 
• Platelet count must be ≥ 100 x 109/L (100,000/µL) 
• All non-hematologic toxicities for which a causal association to study drug cannot be 
ruled out, must be ≤ Grade 2 or returned to baseline; the exceptions to this rule being: 
− Treatment-emergent ocular disorders, which must have recovered to < Grade 1 or 
baseline 
− Treatment-emergent pneumonitis, which must have recovered to ≤ Grade 1 
5.6.1.2. 
Mirvetuximab Soravtansine-related Adverse Events 
Dose modifications for MIRV-related adverse events are described in Table 6.  
Table 6: 
Dose Modifications for Mirvetuximab Soravtansine-related Adverse Events 
Severity Grade 
(CTCAE) 
Dose Modifications for MIRV a 
Hematological  
Neutropenia 
Grade 2 and Grade 3  
Hold drug until ANC is ≥ 1.5 x109/L (1500 /µL) and 
resume at the same dose level  
Grade 4 
Hold drug until ANC is ≥ 1.5 x109/L (1500 /µL) and 
then resume at one lower dose level 
Febrile neutropenia Grade 3 or 4 
(with a single temperature reading ≥ 38.3°C or a 
sustained temperature of > 38°C for > one h) 
Hold drug until ANC is ≥ 1.5 x109/L (1500 /µL) and 
then resume at one lower dose level 
Thrombocytopenia 
Grade 2 and Grade 3  
Hold drug until PLT count is ≥ 100 x 109/L 
(100,000/µL) and resume at same dose level  
Grade 3 associated with clinically significant 
bleeding that requires transfusion therapy and 
Grade 4 
Hold drug until PLT count is ≥ 100 x 109/L 
(100,000/µL) and then resume at one lower level 


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Non-hematological 
Nausea and Vomiting 
Grade 3 (despite use of optimal antiemetics) 
Hold drug until resolved to ≤ Grade 1, then resume 
at one lower level 
Grade 4  
Permanently discontinue 
Diarrhea 
Grade 3 (despite use of optimal anti-diarrheal 
treatment) 
Hold drug until resolved to ≤ Grade 1, then resume 
at one lower level 
Grade 4 
Permanently discontinue 
Ocular Disorders  
Refer to Section 5.6.1.6  
Noninfectious Pneumonitis 
Refer to Section 5.6.1.7 
Infusion-related Reactions 
Refer to Section 5.6.1.9 
All Other Non-hematological Toxicities  
(except AEs related to underlying disease, Grade 3 fatigue, isolated symptomatic Grade 3 biochemistry 
laboratory abnormalities that last for < 7 days including electrolyte abnormalities that respond to 
medical intervention) 
Grade 3  
Hold drug until resolved to ≤ Grade 1, then resume 
at one lower level 
For any Grade 3 hepatic toxicity that does not 
resolve to baseline within seven days, an abdominal 
CT scan must be performed to assess whether it is 
related to disease progression. 
≥ Grade 3 Cardiac events (excluding Grade 3 
hypertension)  
Permanently discontinue 
Grade 4 non-hematological toxicities 
Permanently discontinue 
Abbreviations: CTCAE = common terminology criteria for adverse events; ANC = absolute neutrophil count; PLT = 
platelets; CT = computed tomography; AE = adverse event. 
a Failure to meet retreatment criteria within 1 cycle (21 days) after the missed dose due to insufficient recovery from 
a treatment-related toxicity will results in treatment discontinuation unless otherwise specified in the management 
guidance for a particular toxicity.  
5.6.1.3. 
Mirvetuximab Soravtansine Dose Reduction Dose Levels 
MIRV dose reduction will be as described in Table 7.  


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Table 7: 
Mirvetuximab Soravtansine Dose Reduction Dose Levels 
If the patient was receiving MIRV at: 
Dose should be reduced to: 
6.0 mg/kg AIBW 
5.0 mg/kg AIBW 
5.0 mg/kg AIBW 
4.0 mg/kg AIBW 
4.0 mg/kg AIBW 
Permanently discontinue 
Reduction of MIRV below 4.0 mg/kg will not be permitted. Dose re-escalation is not permitted.  
Abbreviations: AIBW = adjusted ideal body weight; MIRV = mirvetuximab soravtansine. 
5.6.1.4. 
Monitoring and Management of Nausea and Vomiting 
Treatment-related nausea (46% all grade; 1% Grade 3+) and vomiting (16% all grade; 
1% Grade 3+) have been reported in patients treated with MIRV, despite premedication with 
dexamethasone. Therefore, it is recommended that an antiemetic (eg, 5-HT3 serotonin receptor 
antagonists such as palonosetron, granisetron or ondansetron) medication is provided before each 
MIRV dose (Section 5.9.1). Additional antiemetics may be used any time at the discretion of the 
treating physician, according to institutional or other practice guidelines American Society of 
Clinical Oncology (ASCO), ESMO, and NCCN. Patients should be advised to contact their 
treating physician at the first sign of vomiting or worsening nausea.  
5.6.1.5. 
Monitoring and Management of Diarrhea 
Mild to moderate diarrhea has been reported in patients treated with MIRV. 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 suggested regimen would be the 
administration of 2 mg loperamide at the first sign of loose stool, with repeat dosing every 
two hours until symptoms resolve (Wadler 1998). 
5.6.1.6. 
Ocular Disorders 
Changes in visual acuity resulting from reversible keratopathy have been reported in other 
studies of DM4-containing immunoconjugates that use the SPDB linker (Younes 2012). Patients 
receiving MIRV in the Phase 1 and 3 trials (IMGN853-0401, IMGN853-0403) reported ocular 
AEs consistent with reversible keratopathy/corneal epitheliopathy. At the 6 mg/kg AIBW Q3W 
dose level Grade 3 TEAEs of dry eye, keratopathy, vision blurred, eye pain, and photophobia 
were reported in Phase 3 Study IMGN853-403.  
5.6.1.6.1.  Monitoring and Preventive Measures 
In early dose escalation, there was a relationship between MIRV plasma exposure with increased 
likelihood of an ocular event as well as with response. Exposure-response modeling suggested 
that a dose of 6.0 mg/kg AIBW provided adequate exposure for response while also maintaining 
overall exposure within a range that decreased the potential for ocular adverse events. Due to the 
observation of ocular disorders consistent with reversible keratopathy/corneal epitheliopathy in 
patients treated with MIRV, ocular function will be carefully monitored. Ocular symptom 
assessments will be performed at baseline and at Day 1 of every cycle thereafter (Table 2, 


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Table 3, and Table 4). Complete ophthalmologic exams will be performed in all patients at 
baseline and every other cycle thereafter if there is a TEAE reported. 
Patients are advised to avoid using contact lenses while on MIRV. 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. Please refer to Section 5.5.2 and 
Section 5.5.2.1.1 for details on the prophylactic use of steroid eye drops and lubricating artificial 
tears. The use of UVA/UVB sunglasses is recommended in full daylight during the study. The 
use of temporary lower punctal plugs to increase lubrication of the eyes is optional if lubricating 
artificial tears and corticosteroid eye drops are not sufficient. 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 8 should be followed.  
5.6.1.6.2. Management and Dose Modification Guidelines 
If a patient develops ocular symptoms of any grade, the patient is required to have a complete 
examination by an ophthalmologist. If a patient develops ≥ CTCAE Grade 2 ocular symptoms, 
treatment with MIRV must 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. Treatment with MIRV may resume if ocular symptoms improve to Grade 1 or 
baseline within 28 days of the next scheduled MIRV dose (refer to Table 8 for details). If ocular 
symptoms last longer than 28 days, resumption of MIRV may be considered for those patients 
who have experienced clinical benefit if agreed upon between the Sponsor and the Investigator. 
Subsequent eye examinations will be scheduled to occur in every other cycle going forward, 
from the time that the AE was initially reported, and at either the EOT visit or 30-day follow-up 
visit after treatment discontinuation, even if the results of the patient’s ocular exam shows no 
obvious clinical findings. Management of treatment-emergent ocular AEs with inflammatory 
characteristics should include corticosteroid eye drops and/or other measures as indicated by an 
ophthalmologist. 


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Table 8: 
Management of Ocular Symptoms 
Severity Grade 
(CTCAE v5.0 
Grade) 
Management 
Guidelines for MIRV Dose 
Modifications 
Grade 1  
Complete eye exam as outlined in Schedule 
of Assessments (Table 2, Table 3, Table 4) 
Monitor for worsening symptoms 
Continue MIRV dosing 
Grade 2 
Complete eye exam as outlined in Schedule 
of Assessments (Table 2, Table 3, Table 4) 
Repeat complete exam as clinically 
indicated  
Patients should have weekly symptomatic 
ocular assessments by the Investigator until 
the symptoms resolve to Grade 1 or 
baseline or are deemed to be irreversible by 
the Investigator 
Hold MIRV dosing until AE has 
resolved to Grade 1 or better  
Patients with ocular symptoms 
lasting < 14 days may be allowed 
to resume MIRV at the same dose 
level  
Patients with ocular symptoms 
lasting ≥ 14 days but no more than 
28 days may resume MIRV at one 
lower dose level a 
Recurrence of Grade 2 toxicity on 
subsequent cycles despite best 
supportive care will require a 
MIRV dose reduction of one dose 
level 
Grade 3  
Complete eye exam as outlined in Schedule 
of Assessments (Table 2, Table 3, Table 4). 
Repeat complete exam as clinically 
indicated 
Patients should have weekly symptomatic 
ocular assessments by the Investigator until 
the symptoms resolve to Grade 1 or 
baseline or are deemed to be irreversible by 
the Investigator 
Hold MIRV dosing  
Patients may be allowed to resume 
MIRV at a lower dose after AE has 
resolved to Grade 1 or better within 
28 days a 
Recurrence of Grade 3 toxicity on 
subsequent cycles despite best 
supportive care will require a 
MIRV dose reduction of one dose 
level 
Grade 4  
Complete eye exam as outlined in Schedule 
of Assessments (Table 2, Table 3, Table 4). 
Repeat complete exam as clinically 
indicated 
Patients should have weekly symptomatic 
ocular assessments by the Investigator until 
the symptoms resolve to Grade 1 or 
baseline or are deemed irreversible by the 
Investigator 
Permanently discontinue MIRV 
Abbreviations: AE = adverse event; CTCAE = common terminology criteria for adverse events; MIRV = 
mirvetuximab soravtansine. 
a If ocular symptoms last longer than 28 days, resumption of MIRV may be considered for those patients who have 
experienced clinical benefit if agreed upon between the Sponsor and the Investigator. 


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5.6.1.7. 
Monitoring of Non-infectious Pneumonitis 
Non-infectious pneumonitis has been observed after the administration of MIRV. Non-infectious 
pneumonitis 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 other clinically meaningful signs or symptoms of 
pulmonary toxicity, 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. Patients who are asymptomatic may continue dosing of MIRV with 
close monitoring. 
The management and treatment guidelines outlined in Table 9 should be followed. 


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Table 9: 
Management of Non-infectious Pneumonitis 
CTCAE 
v5.0 
Grade 
CTCAE v5.0 
Definition 
Medical Management of 
Pneumonitis 
Guidelines for Dose 
Modificationsa 
Grade 1 
Asymptomatic; 
clinical or 
diagnostic 
observations 
only; 
intervention not 
indicated 
• 
Radiologic assessments (CT scan 
and/or chest x-ray) should be 
performed as clinically indicated. 
• 
Monitor for pulmonary 
symptoms. 
• 
Continue dosing in 
asymptomatic patients 
and monitor closely.  
Grade 2 
Symptomatic; 
medical 
intervention 
indicated; 
limiting 
instrumental 
ADL 
• 
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. 
• 
Hold dosing until 
symptoms resolve to 
≤ Grade 1. 
• 
MIRV may be resumed 
at same dose level or 
one dose level lower 
after discussion with the 
Sponsor. 
Grade 3 
 
 
 
 
 
Grade 4 
Severe 
symptoms; 
limiting self-
care ADL; 
oxygen 
indicated 
 
Life-threatening 
respiratory 
compromise; 
urgent 
intervention 
indicated (eg, 
tracheotomy or 
intubation) 
• 
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.  
• 
Bronchoscopy with lavage and/or 
biopsy when clinically feasible 
should be performed.  
• 
The pneumonitis event must be 
followed until resolution. 
• 
Permanently discontinue 
MIRV.  
Abbreviations: ADL = activities of daily living; AE = adverse event; CT = computed tomography; MIRV = 
mirvetuximab soravtansine. 
a Failure to meet retreatment criteria within 1 cycle (21 days) after the missed dose due to insufficient recovery from 
a treatment-related toxicity will results in treatment discontinuation unless otherwise specified in the management 
guidance for a particular toxicity.  
5.6.1.8. 
Management of Electrolytes Imbalance 
Prompt attention should be given to the correction of potential electrolytes imbalance, especially 
hypokalemia and hypomagnesemia. 


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5.6.1.9. 
Potential Infusion-related Reactions 
Some patients treated with IV infusions of therapeutic drugs have experienced concurrent 
infusion-related reactions (IRR) (see CTCAE Version 5.0). 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 IRRs and for subsequent retreatment are 
provided in Table 10. Delayed IRRs 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 ≥ Grade 2 IRR during or immediately after administration of MIRV will 
have blood drawn for determination of drug concentration and antibodies to MIRV (ADA). The 
sample should be obtained within three hours of the onset of the reaction and one week later. 
Such patients should undergo all scheduled efficacy and safety evaluations. 


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Table 10: 
Management Guidelines for Potential Infusion-related Reactions 
Infusion Reaction 
CTCAE v5.0 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 (Q4h) prn for nausea  
• 
Diphenhydramine (or equivalent) 25-50 mg PO or IV prn 
• 
Methylprednisolone (or equivalent) 125 mg IV prn 
Grade 2: Moderate  
• 
Interrupt infusion and disconnect infusion tubing from patient 
• 
Promethazine (or equivalent) 150 mg PO per day (Q4h) prn for nausea 
• 
Diphenhydramine (or equivalent) 25-50 mg PO or IV prn 
• 
Acetaminophen (or equivalent) 650 mg PO prn 
• 
Methylprednisolone (or equivalent) 125 mg 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 pre-
medicated with Dex (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 min before 
dosing.  
Grade 3: Severe, 
prolonged reaction not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion; recurrence 
of symptoms after initial 
improvement; 
hospitalization indicated 
for clinical sequelae 
OR 
Grade 4: Life-
threatening 
consequences, urgent 
intervention indicated 
• 
Immediately stop infusion and disconnect infusion tubing from patient. 
• 
Administer diphenhydramine (25-50 mg) IV (or equivalent) 
• 
Administer IV steroids (methylprednisolone (or equivalent) up to 
0.5mg/kg Q 6h) 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 only be used if 
all other treatment methods fail to manage the IRR. 
• 
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 
Abbreviations: BID = twice a day; CTCAE = common terminology criteria for adverse events; Dex = 
dexamethasone; IM = intramuscular; IRR = infusion related reaction; IV = intravenously; PO = orally; prn = as 
needed; SAE = serious adverse event; SQ = subcutaneous.  
 


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5.6.1.10. Discontinuation of Mirvetuximab Soravtansine Due to Toxicity 
MIRV should be discontinued in the case of the following treatment-related events: 
• Grade ≥ 3 cardiac event (excluding Grade 3 hypertension) (Section 5.6.1.2) 
• Grade ≥ 3 pneumonitis event (Section 5.6.1.7) 
• Non-hematologic events of Grade 4 severity (Section 5.6.1.2) 
• Ocular events of Grade 4 severity (Section 5.6.1.6) 
• Failure to meet re-treatment criteria within 1 cycle (21 days) after the missed dose 
due to insufficient recovery from a treatment-related toxicity unless otherwise 
specified in the management guidance for a particular toxicity. In such cases, 
continuation of MIRV may be considered for those patients who have experienced 
clinical benefit if agreed upon between the Sponsor and the Investigator. 
5.6.2. 
Paclitaxel 
Label warnings, manufacturer’s recommendations and standard clinical practice should be 
followed. Guidelines for dose interruptions and dose modifications are described in Table 11. 
 


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Table 11: 
Paclitaxel Dose Modification Guidelines 
Severity Grade 
(CTCAE v5.0 Grade) 
Dose Modification 
Hematological Toxicities 
Grade 1 
No action 
Grade 2 & 3 
Hold Pac until ANC and PLT levels meet the following criteria: 
Day 1: ANC ≥ 1.5 x 109/L (1,500/μL) and platelets ≥ 100 x 109/L 
(100,000/μL) 
Day 8, 15 & 22: ANC ≥ 1.0 x 109/L (1,000/μL) and platelets 
≥ 100 x 109/L (100,000/μL)  
Resume treatment at same dose level 
Grade 4 
Hold Pac until ANC and PLT levels meet the following criteria: 
Day 1: ANC ≥ 1.5 x 109/L (1,500/μL) and platelets ≥ 100 x 109/L 
(100,000/μL) 
Day 8, 15 & 22: ANC ≥ 1.0 x 109/L (1,000/μL) and platelets 
≥ 100 x 109/L (100,000/μL) 
Dose reduce by 1 level and/or omit D22 dose 
For febrile neutropenia and/or severe bleeding, permanently discontinue Pac 
Non-hematological Toxicities 
Grade 1 
No action 
Grade 2 
No action; for patients experiencing neurotoxicity, dose reduce by 1 level 
and/or omit D22 dose. 
Grade 3 
Dose reduce by 1 level and/or omit D22 dose. 
Grades 3 and 4 
Hold Pac until the event resolves or improves to Grade 1. Dose reduce by 
1 level and/or omit D22 dose. 
Abbreviations: ANC = absolute neutrophil count; CTCAE = common terminology criteria for adverse events; D = 
day; Pac = paclitaxel; PLT = platelet.  
Administration of granulocyte colony stimulating factor (G-CSF) or erythropoietin (EPO) is 
permitted as per institutional guidelines.  
5.6.2.1. 
 
Dose Reduction Dose Levels 
Pac dose reduction will be as described in Table 12.  
Table 12: 
Paclitaxel Dose Reductions 
If the patient was receiving Pac at: 
Dose should be reduced to: 
80 mg/m2 
70 mg/m2 
70 mg/m2 
60 mg/m2 
* Reduction of the Pac below 60 mg/m2 will not be permitted. Instead of a second dose reduction, 70 mg/m2 can be 
maintained if one weekly dose is omitted within 1 cycle. Dose re-escalation is not permitted. 


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5.6.2.2. 
Criteria for Permanent Discontinuation of Paclitaxel 
Pac will be permanently discontinued for febrile neutropenia and/or severe bleeding.  
5.6.3. 
Topotecan 
Label warnings, manufacturer’s recommendations and standard clinical practice should be 
followed. Guidelines for dose interruptions and dose modifications are described in Table 13.  
Table 13: 
Topotecan Dose Modification Guidelines 
Severity Grade  
(CTCAE V5.0 Grade) 
Dose Modification 
Hematological Toxicities 
Grade 1 
No action required. 
Grades 2 or 3 
Hold Topo until ANC and PLT levels meet the following criteria: 
Day 1: ANC ≥ 1.5 x 109/L (1,500/μL) and platelets ≥ 100 x 109/L 
(100,000/μL) 
Day 8, & 15: ANC ≥ 1.0 x 109/L (1,000/μL) and platelets ≥ 100 x 109/L 
(100,000/μL)  
Re-treat at same dose level. 
Grade 4 or any grade 
neutropenia complications 
(fever, infection)  
Hold Topo until ANC and PLT levels meet the following criteria: 
Day 1: ANC ≥ 1.5 x 109/L (1,500/μL) and platelets ≥ 100 x 109/L 
(100,000/μL) 
Day 8, & 15: ANC ≥ 1.0 x 109/L (1,000/μL) and platelets ≥ 100 x 109/L 
(100,000/μL)  
Dose reduce by one level.  
Non-hematological Toxicities 
Grade 1 
No action required. 
Grade 2 
No action required. 
Grades 3 or 4 
Hold Topo until the event improves to Grade 1 or resolves. Dose 
reduce by one level. 
Abbreviations: CTCAE = common terminology criteria for adverse events; ANC = absolute neutrophil count; PLT = 
platelets. 
Administration of G-CSF or EPO is permitted according to approved institutional guidelines.  
Patients who receive Topo and develop a TEAE requiring an interruption of Topo may resume 
treatment at a reduced dose level as shown in Table 14. 
5.6.3.1. 
Dose Reduction Dose Levels 
Topo dose reduction will be as described in Table 14 and Table 15. 


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Table 14: 
Topotecan Dose Reductions (Weekly Schedule) 
If the patient was receiving Topo at: 
Dose should be reduced to: 
4 mg/m2 
3.5 mg/m2 
3.5 mg/m2 
3 mg/m2 
* Reduction of the Topo below 3mg/m 2will not be permitted. Dose re-escalation is not permitted. 
Table 15: 
Topotecan Dose Reductions (Five Days Schedule) 
If the patient was receiving Topo at: 
Dose should be reduced to: 
1.25 mg/m2 
1.0 mg/m2 
1.0 mg/m2 
0.75 mg/m2 
* Reduction of the Topo below 0.75mg/m2 will not be permitted. Dose re-escalation is not permitted. 
5.6.3.2. 
Criteria for Permanent Discontinuation of Topotecan 
Treatment should be permanently discontinued according to the guidelines shown in Table 16, in 
case the observed TEAE is unmanageable despite dose reductions. 
Table 16: 
Adverse Events Requiring Permanent Discontinuation of Topotecan 
Severity Grade 
(CTCAE v5.0 Grade) 
Adverse Event 
Hematological Toxicities 
Grade 4 
ANC < 0.5 x 109/L for more than two weeks 
Grade 4 
Thrombocytopenia for more than 2 weeks 
Non-hematological Toxicities 
Grade 3 or 4 
Mucositis 
Grade 3 or 4 
Neurotoxicity 
Grade 3 or 4 
Toxicities (except nausea, vomiting, and alopecia) lasting for more than 
three weeks 
5.6.4. 
Pegylated Liposomal Doxorubicin 
Label warnings, manufacturer’s recommendations and standard clinical practice should be 
followed.  
5.6.4.1. 
Hematological Toxicities 
Patients receiving PLD are at risk of bone marrow suppression. Leukopenia is usually transient; 
hematological AEs may require dose delays or reductions as indicated in Table 17. 


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Table 17: 
Pegylated Liposomal Doxorubicin Dose Modification Guidelines for 
Hematological Adverse Events 
Severity 
Grade 
ANC 
Platelets 
Modification 
Grade 1 
< LLN to 1.5 x 109/L 
(< LLN to 1,500/μL) 
< LLN to 75.0 x 109/L 
(< LLN to 75,000/μL) 
Resume treatment; no dose reduction 
Grade 2  
< 1.5 to1.0 x 109/L 
(< 1,500 to 1,000/μL) 
< 75.0 to 50.0 x 109/L 
(< 75,000 to 50,000/ μL) 
Delay until ANC 1.5 x 109/L 
(≥ 1,500/μL) and platelets ≥75.0 x 
109/L (75,000/μL); re-dose with no 
dose reduction 
Grade 3 
< 1.0 to 0.5 x 109/L 
(< 1,000 to 500/μL) 
< 50.0 to 25.0 x 109/L 
(50,000 to 25,000/ μL) 
Delay until ANC 1.5 x 109/L 
(≥ 1,500/μL) and platelets ≥75.0 x 
109/L (75,000/μL); re-dose with no 
dose reduction 
Grade 4 
< 0.5 x 109/L 
(< 500/μL) 
< 25.0 x 109/L 
(< 25,000/ μL) 
Delay until ANC 1.5 x 109/L 
(≥ 1,500/μL) and platelets ≥75.0 x 
109/L (75,000/μL); re-dose at 25% 
dose reduction or continue previous 
dose with cytokine support 
5.6.4.2. 
Non-hematological Toxicities 
5.6.4.2.1. Hand-foot Syndrome 
Hand-foot syndrome (HFS) 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. 
HFS has been observed in patients receiving PLD at doses of 50 mg/m2 and, with less frequency, 
in those receiving PLD at 30 mg/m2. If patients present with symptoms/signs consistent with 
HFS, the dose of PLD should be modified as indicated in Table 18.  


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Table 18: 
Pegylated Liposomal Doxorubicin Dose Modification Guidelines for Hand-
foot Syndrome and Mucositis 
Severity 
Grade 
(CTCAE v5.0 
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 PLD, unless previous 
Grade 3 or 4 HFS.  
In case of previous Grade 3/4 HFS, 
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 PLD until resolved to Grade 1 
or baseline. If after 2 weeks there is 
no resolution, PLD should be 
discontinued. If no prior Grade 3-4 
HFS, resume at the dose preceding 
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 PLD until resolved to Grade 1 
or baseline. Decrease dose by 25%. 
If after 2 weeks there is no 
resolution, PLD should be 
discontinued. 
Grade 4 
Diffuse or local 
process causing 
infectious 
complications, a bed 
ridden state, or 
hospitalization. 
Requires parenteral or 
enteral support 
Abbreviations: PLD = pegylated liposomal doxorubicin; HFS = hand-foot syndrome. 
If patients receiving PLD experience a TEAE, their PLD dose should be reduced as indicated in 
Table 19. Patients who require dose reductions below 20 mg/m2 should discontinue their PLD 
treatment. 
5.6.4.2.2. Cardiac Toxicity 
Patients receiving PLD are at risk for cardiac toxicity. Cardiac function should be carefully 
monitored in these patients. If the patient’s LVEF drops below normal or by at least 15% from 
the baseline value, study drug should be interrupted and event should be discussed with Sponsor 
before resuming treatment.  


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5.6.4.3. 
Criteria for Permanent Discontinuation of PLD  
Patients who require dose reductions below 20 mg/m2 should permanently discontinue their PLD 
treatment. 
5.6.4.4. 
Dose Reduction Dose Levels 
PLD dose reduction will be as described in Table 19.  
Table 19: 
Pegylated Liposomal Doxorubicin Dose Reductions 
If the patient was receiving PLD at: 
Dose should be reduced to: 
40 mg/m2 
30 mg/m2 
30 mg/m2 
20 mg/m2* 
* Reduction of the PLD dose below 20 mg/ m2 will not be permitted. Patients who require dose reductions below 
20 mg/m2 should discontinue their PLD treatment. Dose re-escalation is not permitted. 
5.7. 
Discontinuation of the Patients from the Study or Study Treatment 
5.7.1. 
End of Treatment 
Patients will continue to receive study drug until they present with PD per RECIST 1.1, as 
assessed by study Investigator, unacceptable toxicity, withdraw consent, or death, whichever 
comes first, or until the Sponsor terminates the study. Study treatment and/or participation in the 
study may be discontinued at any time at the discretion of the Investigator. The following may be 
reasons for the Investigator to remove a patient from the study drug: 
• The patient suffers an intolerable AE 
• Noncompliance, including failure to appear at one or more study visits 
• The patient was erroneously included in the study 
The reason for treatment discontinuation must be captured in the EOT electronic case report 
form (eCRF). Any AEs experienced up to the point of discontinuation and 30 days thereafter 
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. Patients will continue to be 
followed for PFS2 and OS, after discontinuing study drug (Section 10.3.3).  
5.7.2. 
End of Study  
Discontinuation from participation in the study will be documented on the EOS eCRF. Reasons 
for EOS include withdrawal of consent, lost to follow-up, death, or study termination by 
Sponsor.  
5.7.3. 
Withdrawal of Consent 
The patient or legally authorized representative acting on behalf of the patient is free to withdraw 
consent to study treatment and/or participation in the study at any time irrespective of the reason. 


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The Investigator must make every effort (eg, telephone, email, letter) to determine the primary 
reason for this decision and record this information. Study treatment must be discontinued, and 
no further assessments conducted. Further attempts to contact the patient are not allowed unless 
safety findings require communication or follow-up. If the patient or legally authorized 
representative withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before withdrawal of consent. All biological samples that 
have been already collected will be retained and analyzed at a later date. The patient or legally 
authorized representative may request destruction of any samples, and the Investigator must 
document this in the site study records. The Statistical Analysis Plan (SAP) will specify how 
early withdrawals from treatment will be accounted for in the analyses of efficacy endpoints. 
Patients who have withdrawn from the study cannot be re-treated in the study and their inclusion 
and patient number must not be reused. 
5.7.4. 
Lost to Follow-up 
A study patient will be considered lost to follow-up if the patient repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. The Investigator should make all 
efforts to contact the patient and to determine the patient’s health status, including at least her 
vital status (in accordance with applicable regulations related to privacy and confidentiality). A 
patient should not be considered lost to follow-up until due diligence has been completed and 
documented. The following actions must be taken if a patient fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in 
the study. 
• In cases in which the patient is deemed lost to follow-up, the Investigator or designee 
must make every effort to regain contact with the patient (where possible, 3 telephone 
calls and, if necessary, a certified letter to the patient’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the 
patient’s medical record. 
Should the patient continue to be unreachable, he/she will be considered to have withdrawn from 
the study with a primary reason of lost to follow-up. 
5.8. 
Period of Observation 
For purposes of this study, the period of safety observation extends from the time of pre-
screening informed consent until the 30-day follow-up safety visit unless additional follow-up 
safety information is requested as described in Section 9.1 and Section 10.3.1. Short-term 
follow-up for patients who discontinue study drug without documented PD will be followed per 
RECIST 1.1 every 6 weeks (± 1 week) from C1D1 for the first 36 weeks then every 12 weeks 
(± 3 weeks) until PD, until the patient begins subsequent anticancer treatment, the patient dies, or 
the patient withdraws consent, whichever comes first. All patients will be followed every 3 


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months (± 1 month) for survival until death, lost to follow-up, withdrawal of consent for survival 
or until EOS, whichever comes first. 
5.9. 
Concomitant Medications and Procedures 
All concomitant medications and supportive therapy taken 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). 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. 
5.9.1. 
Antiemetic and Antidiarrheal Medications 
An antiemetic (eg, 5-HT3 serotonin receptor antagonists such as palonosetron, granisetron or 
ondansetron) medication is recommended before each MIRV dose; additional antiemetics and/or 
antidiarrheal (eg, loperamide) medications may be used any time at the discretion of the treating 
physician. 
5.9.2. 
Folate-Containing Supplements 
Folate-containing supplements should not be taken during the study. 
5.9.3. 
Antineoplastic Therapy 
All non-study related antineoplastic therapy including but not limited to cytotoxic, 
immunotherapy, and VEGF-targeted therapy, is prohibited while on study drug.  
5.9.4. 
Hematopoietic Growth Factors 
Patients receiving recombinant EPO or darbepoetin-α before study start may continue to receive 
pretreatment doses.  
The use of erythropoietic and granulocyte growth factors in accordance with ASCO guidelines 
may be implemented at the discretion of the treating physician. 
5.9.5. 
Anticoagulants 
The use of anticoagulant agents is allowed. Please see Section 5.9.8 if using apixaban and 
rivaroxaban due to CYP3A interaction potential. 
5.9.6. 
Methods of Contraception 
Women of childbearing potential must agree to use highly effective contraceptive method(s) 
while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months 
after the last dose of Pac, PLD, or Topo. A woman of childbearing potential is a woman who is 
considered fertile, following menarche and until becoming post-menopausal unless permanently 
sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and 
bilateral oophorectomy. 


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The following birth control methods may be considered highly effective (failure rate of less than 
1% per year): 
• Combined (estrogen and progesterone) hormonal contraception associated with inhibition 
of ovulation 
o Oral 
o Intravaginal  
o Transdermal 
• 
Progesterone-only hormonal contraception associated with inhibition of ovulation: 
o Oral 
o Injectable 
o Implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomized partner  
• Sexual abstinence 
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 IECs /IRBs. Periodic abstinence (eg, calendar, 
ovulation, symptom-thermal, post-ovulation methods, etc) and withdrawal are not acceptable 
methods of contraception.  
If a contraceptive method listed above is restricted by local regulations/guidelines, then it does 
not qualify as an acceptable method of contraception for patients participating at sites in this 
country/region. 
Patients should be informed that taking the study medication may involve unknown risks to the 
fetus (unborn baby) if pregnancy were to occur during the study. To participate in the study 
WCBP must adhere to the contraception requirement (described above) from the day of study 
medication initiation (or 14 days before the initiation of study medication for oral contraception) 
through the duration of study treatment. Contraception requirements must be adhered to for at 
least 3 months after the last dose of MIRV and at least six months after the last dose of Pac, 
Topo and PLD. If there is any question that a WCBP will not reliably comply with the 
requirements for contraception, that patient should not be entered into the study. 
5.9.7. 
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-moderate infusion reactions. Additionally, medications (not addressed 


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above) used to treat underlying medical conditions at study entry including antiemetics and 
antidiarrheals will be allowed to continue.  
5.9.8. 
Medications that are CYP3A or MDR1 Substrates or CYP3A Substrates with 
Narrow Therapeutic Index 
In vitro metabolism studies demonstrated that DM4 is predominantly metabolized by thiol s-
methyltransferase (TMT) 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 CYP3A, its 
exposure could potentially be increased in the presence of strong CYP3A inhibitors. Drinking 
greater than one serving (250 mL) of grapefruit juice per day should be avoided. 
Both DM4 and S-methyl DM4 are substrates for MDR1 efflux transporter. Their exposure could 
potentially increase in the presence of MDR1 efflux transporter. In vitro metabolism data also 
indicates that DM4 is a time-dependent inhibitor of CYP3A4. The risk of a significant in vivo 
drug-drug interaction caused by inhibition of CYP3A4 or MDR1 is unknown. Treatment of 
patients with concomitant medications that are inhibitors of MDR1, sensitive substrates of 
CYP3A, or are CYP3A substrates with a narrow therapeutic index should be carefully monitored 
(Appendix D).  
5.10. 
Overdose and Medication Error 
5.10.1. 
Overdose 
There is no known treatment/antidote available for MIRV. For IC Chemo agents, please follow 
management guidelines for overdose as described in the prescribing information and/or 
institutional guidelines. Supportive measures should be instituted if an instance arises in which a 
patient suffers an overdose of any study drug. 
5.10.2. 
Medication Error 
The Sponsor must be notified within 24 hours of any error leading to the administration of either 
10% more or 10% less than the intended dose; in such cases, the event must be reported on the 
eCRF. If an error resulted in a SAE, a Serious Adverse Event form must be submitted within 
24 hours of the event (see Section 9.2.1). 
6. 
PHARMACOKINETIC AND IMMUNOGENICITY 
ASSESSMENTS 
6.1. 
Pharmacokinetic Assessments – Mirvetuximab Soravtansine 
The PK properties of MIRV and key metabolites will be evaluated following IV administration, 
as outlined in Table 2 and Table 20. Plasma samples will be collected to determine the 
concentration of MIRV (conjugate, total Ab, free DM4, S-methyl DM4 and possibly other 
metabolites). 
Blood samples for PK analysis will be taken at the following time points:  


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Table 20: 
Pharmacokinetics Sampling Time Points 
Visit 
Time Point 
C1D1 
≤ 1 hour after MIRV infusion 
C1D8 
Anytime during visit 
C2D1 
Before dosing 
C3D1 
≤ 1 hour after MIRV infusion 
C3D8 
Anytime during visit 
C4D1 
Before dosing 
EOT 
Anytime during visit 
30-day Follow-up 
Anytime during visit 
Abbreviations: C = cycle; D = day; EOT = End of Treatment. 
Unscheduled visit: Any patient who experiences a ≥ Grade 2 IRR during or within 3 hours after 
the administration of MIRV will have blood drawn within three hours of the onset of the reaction 
and one week later for determination of drug concentration and antibodies to MIRV (ADA). 
PK 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. 
Procedures for collection, storage and shipment of samples are provided in the applicable 
Laboratory Manual. 
6.2. 
Immunogenicity Assessments – Mirvetuximab Soravtansine 
The potential immunogenicity against MIRV will be assessed at C1D1, C2D1, C4D1, EOT, and 
30-Day Follow-up, as outlined in Table 2. The potential impact of immunogenicity on PK, 
safety, and efficacy of MIRV and total Ab will be explored.  
The sample for ADA analysis is taken from the PK tube predose on Day 1 of Cycles 2, and 4 and 
at the EOT and 30-day Follow-up visits. There will be an ADA only collection prior to dosing on 
Day 1 of Cycle 1. 
7. 
BIOMARKER RESEARCH STUDIES 
7.1. 
Evaluation of FRα Expression in Tumor Tissue 
FRα expression varies with tumor histology, as reported in the literature and demonstrated in 
preclinical studies (Section 1.1 and Investigator Brochure). FRα expression in tumor samples 
will be analyzed using the Ventana FOLR1 (FOLR1-2.1) CDx assay an immunohistochemical 
assay developed to detect FRα in cut slide specimens of formalin-fixed, paraffin embedded 
(FFPE) epithelial ovarian cancer tissue stained on the BenchMark ULTRA automated staining 
instrument using the Ventana OptiView DAB IHC Detection Kit. This assay will be conducted at 
a central laboratory. All patients must submit tumor tissue, or FFPE slides for analysis of FRα 


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expression prior to enrollment. PS2+ is the terminology used to reference a scoring method 
based on membrane stain intensity level of 2 or greater. The PS2+ scoring method requires the 
pathologist (at the central laboratory) to assess the percentage of tumor cells with moderate (2) 
and/or strong (3)membrane staining compared to the total number of viable tumor cells. To be 
considered positive for FRα expression and eligibility for the study, ≥ 75% of viable tumor cells 
must exhibit level 2 and/or 3 membrane staining intensity. 
Only patients with the required FRα expression levels by Ventana FOLR1 (FOLR1-2.1) CDx 
assay are eligible to enroll in the study (see the Investigator Brochure Section 5 for details on the 
assay and the FRα expression threshold selected for this study). If a patient wishes to enroll and 
does not have archival material available for analysis, she must undergo a biopsy to assess FRα 
expression. Patients for whom the only sites of disease would require biopsy procedures 
considered to be of significant risk must not be enrolled in the study. These procedures include 
(but are not limited to) biopsies of the brain, lung/mediastinum, pancreas, or endoscopic 
procedures extending beyond the esophagus, stomach or bowel.  
Instructions regarding processing and shipment of all samples for FRα testing are detailed in the 
applicable Laboratory Manual. 
7.2. 
Exploratory Biomarker Studies 
Studies in tumor tissue and blood will be performed to explore potential biomarkers of MIRV 
sensitivity and resistance. The sections below describe activities that are planned, but other 
additional biomarkers/biological pathways may be investigated based on emerging data. 
7.2.1. 
Soluble FRα 
An exploratory endpoint of the study is to assess if Soluble FRα levels in blood at pre-screening 
are predictive or prognostic of response to MIRV or IC Chemo. The blood sample collected 
during pre-screening will only be used for the measurement of Soluble FRα. 
7.2.2. 
Potential Predictive Markers of Drug Response 
The molecular characterization of enrolled patient’s tumor tissue may be conducted to determine 
the relationship between molecular alterations and clinical response, which may help identify 
patients who are most likely to benefit from treatment with MIRV or IC Chemo. Next-generation 
sequencing techniques may be used to evaluate somatic mutations, copy number variations, 
rearrangements, and expression patterns of multiple genes and/or proteins commonly altered in 
solid tumors. 
New assays for candidate biomarkers associated with sensitivity or resistance to MIRV or IC 
Chemo, identified in the current study or earlier studies, may also be developed and tested on 
patient samples. 
7.2.3. 
Future Use of Biomarker Samples 
For patients who consent to it, unused tumor tissue after biomarker testing may be used for other 
research purposes. These other research analyses will help to understand either disease subtypes 
or drug responses, to develop and/or validate a bioassay method, or to identify new drug targets 


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or biomarkers. These samples will remain labeled with the same identifiers used during the 
study, ie, patient ID. They will be transferred to the Sponsor (or a subcontractor site), which can 
be located outside of the country where the study is conducted. The Sponsor has included 
safeguards for protecting patient confidentiality and personal data (Section 13.3). 
8. 
STUDY PROCEDURES 
8.1. 
Informed Consent 
Each patient or legally authorized representative will sign an IRB/IEC-approved ICF before any 
study-required procedures are conducted, unless those procedures are performed as part of the 
patient’s standard care (Table 2, Table 3, and Table 4). Patient must be re-consented to the most 
current version of the ICF(s) per IRB/IEC guidelines during their participation in the study. 
Patients will sign a pre-screening ICF to allow testing of fresh or archival tumor tissue by the 
assay required for study inclusion and collection of a blood sample for the measurement of 
Soluble FRα. If patients meet entry criteria for FRα positivity (high FRα) they will sign the main 
study ICF and proceed with remaining screening procedures per the Schedule of Assessments. In 
some cases, the pre-screening ICF and main study ICF may be merged into a single ICF based on 
site-specific guidelines or preference. 
8.2. 
Inclusion and Exclusion Criteria 
The inclusion and exclusion criteria are assessed during Screening (within 28 days before the 
first dose of any study drug on Cycle 1, Day 1). All screening evaluations must be completed and 
reviewed prior to first dose to confirm that potential patients meet all eligibility criteria. The 
Investigator will maintain a screening log to record details of all patients 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 utilized for 
screening or baseline purposes provided the procedure met the protocol-specified criteria and 
were performed within the timeframe defined in the Schedule of Assessments. A patient is 
considered enrolled when randomized to a study treatment (Table 2, Table 3, and Table 4). 
8.3. 
Confirmation of Disease Diagnosis 
At Screening, disease diagnosis, and current disease status are confirmed from information in the 
source record (Table 2, Table 3, and Table 4). 
8.4. 
BRCA Mutation Status 
The BRCA mutation status from prior testing (information in the source record) will be recorded 
(Table 2, Table 3, and Table 4). Patients with a BRCA mutation (germline mutation or somatic 
mutation in tumor tissue) are classified as positive and patients who were tested and shown to not 
have a BRCA mutation will be classified as negative. Patients without known BRCA mutation 
status in the source record are classified as unknown. If a patient with unknown status is tested 


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and is found to have a BRCA mutation, this patient is considered BRCA mutation positive in 
analyses. 
8.5. 
Demographic/Medical History 
The age, race, and gender of the patient are to be recorded during Screening for all patients who 
consent to the study (Table 2, Table 3, and Table 4). 
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 
include a description of all prior therapies for the primary malignancy. 
8.6. 
Physical Examination, Weight, and Height 
Physical examination (PE), height (Screening only) and weight must be performed as indicated 
in the Schedule of Assessments (Table 2, Table 3, and Table 4). A complete PE, including 
assessments 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 at the 30-day Follow-up Visit. Directed PEs will be completed at additional time 
points as specified in the Schedule of Assessments. 
8.7. 
Vital Signs 
Vital signs include BP and body temperature. These signs are measured as outlined in Table 2, 
Table 3, and Table 4. 
8.8. 
Electrocardiogram (ECG) 
A standard, single 12-lead ECG will be performed within 14 days prior to first dose to determine 
study eligibility.  
8.9. 
Ocular Symptom Assessment and Ophthalmic Examination 
8.9.1. 
Ocular Symptom Assessment 
Ocular symptom assessment will be performed at screening for all treatment arms. Ocular 
symptom assessment will be performed before the start of each cycle for patients in Arm 1 by the 
treating physician or other qualified individual. For patients reporting > CTCAE Grade 1 ocular 
symptoms, study drug will be held until the patient is evaluated by an ophthalmologist for a 
complete examination. The ocular symptom assessment will also be performed at EOT and the 
30-day Follow-up (Table 2, Table 3, and Table 4). 
8.9.2. 
Ophthalmic Examination 
An ophthalmic examination will be performed at Screening (within 14 days prior to first dose of 
study drug) by an ophthalmologist and will include the following: distant visual acuity, best 
corrected visual acuity, slit lamp examination, intraocular pressure measurement, and indirect 
fundoscopy. Patients who experience ocular TEAEs while on study will have a complete 
ophthalmologic exam performed at the emergence of the symptoms and at every other cycle 


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thereafter. All patients who had an ophthalmic exam on study treatment (post-baseline) will have 
a complete ophthalmologic exam performed at the EOT visit or 30-day follow-up visit (Table 2, 
Table 3, and Table 4). 
8.10. 
Laboratory Assessments 
Local laboratories will be used for the analysis of scheduled hematology, biochemistry, 
coagulation and other tests collected as part of safety monitoring. Screening labs (Table 21) will 
be performed within 14 days of first dose. Repeat testing on Cycle 1, Day 1 is not required if 
tests were obtained within 4 days of dosing and are within acceptable ranges. Repeat testing will 
be performed as outlined in the Schedule of Assessments (Table 2, Table 3, and Table 4) and as 
clinically indicated.  
Note that before each administration of study drug, laboratory results must be reviewed to 
evaluate for potential toxicity.  
8.10.1. 
Clinical Laboratory Panels 
A list of clinical laboratory tests may be found in Table 21. 
Table 21: 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Urinalysis 
(Screening only) 
Coagulation 
(Screening only) 
• 
Hematocrit 
• 
Hemoglobin 
• 
WBC (with 5-part 
differential)  
• 
Platelet count 
• 
Albumin 
• 
Alkaline 
phosphatase 
• 
ALT 
• 
AST 
• 
BUN or Urea 
• 
Calcium 
• 
Chloride 
• 
Creatinine 
• 
Glucose 
• 
Magnesium 
• 
Phosphorus 
• 
Potassium  
• 
Sodium 
• 
Total bilirubin 
• 
pH 
• 
Ketones 
• 
Protein 
• 
Glucose 
• 
Occult blood 
• 
Leukocyte esterase 
• 
Nitrite 
• 
PT or INR/aPTT 
Abbreviations: ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; INR = international normalized ratio; PT = prothrombin time; WBC 
= white blood cell count. 


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8.11. 
Pregnancy Screen 
All WCBP will complete a serum beta-human chorionic gonadotropin (β-hCG) or urine 
pregnancy test within 4 days before the first dose of study drug and urine or serum pregnancy 
tests within 4 days prior to Day 1 of each cycle and at the 30-day Follow-Up visit. It is 
recommended to perform monthly pregnancy tests for 3 months after the last dose of MIRV and 
for 6 months after the last dose of chemotherapy. Additional testing may be performed in 
accordance with institutional requirements or local regulation. Pregnancy tests must be negative 
for the patient to be enrolled and to continue to receive the study drug (Table 2, Table 3, and 
Table 4). 
If a patient becomes pregnant or suspects pregnancy while participating in this study, the 
Investigator and Sponsor must be informed immediately (Section 9.2.2) and the patient will be 
withdrawn from study drug. See Section 9.2.2 for more details.  
8.12. 
Eastern Cooperative Oncology Group Performance Status 
ECOG PS (Appendix A) will be assessed during Screening and at other times specified in the 
Schedule of Assessments (Table 2, Table 3, and Table 4). An assessment is not necessary on Day 
1 of Cycle 1 if the Screening assessment was obtained within the prior 4 days.  
8.13. 
ECHO/MUGA Scan 
ECHO or MUGA scans will be performed only in patients receiving PLD (Table 4). ECHO or 
MUGA scans will be performed at Screening and as clinically indicated. The same test should be 
performed throughout the trial.  
8.14. 
Tumor Response Assessment 
8.14.1. 
Radiological Imaging 
Radiologic tumor evaluation by CT or MRI of chest, abdomen, and pelvis will be performed 
within 28 days before first dose of study drug and every 6 weeks (±1 week) from C1D1 for the 
first 36 weeks on study and every 12 weeks (±3 weeks) thereafter (Table 2, Table 3, and 
Table 4). Patients who discontinue study treatment for reasons other than progressive disease 
(PD) will continue with tumor assessments until documentation of PD or the start of a new 
anticancer therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments 
should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an 
interval of no more than 12 weeks. After Week 36, assessment will occur every 12 weeks (± 3 
weeks) until documentation of PD or the start of new anticancer therapy. The same method of 
radiographic assessment used at Screening must be used at all subsequent radiographic 
evaluations. Copies of all imaging scans must be obtained and sent to a central imaging vendor 
designated by ImmunoGen as outlined in the Imaging Manual. The central imaging vendor will 
assess the quality of the images. The imaging vendor will be responsible for the formation and 
management of the blinded independent central review (BICR). 
Tumor response will be assessed by the Investigator using RECIST 1.1 (Eisenhauer 2009). 
Response as determined by the Investigator will be recorded in the clinical trial database. If the 


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primary endpoint (PFS by Investigator) is statistically significant at the final analysis, the BICR 
assessment will be used for a sensitivity analysis of PFS and objective response rate (ORR).  
The central imaging vendor will ensure that the central radiologists remain blinded to the local 
assessment from the Investigator and other unblinding information. This and all other imaging 
procedures will be documented in an independent review charter agreed upon between 
ImmunoGen and the imaging vendor before initiation of any BICR reviews. 
Note: It is very important that the same method of radiologic assessment be used 
throughout the study and that the same lesions are followed.  
8.14.2. 
CA-125 
Serum CA-125 assessments (Appendix C) will be performed within 14 days prior to the first 
dose of study drug, and at each radiologic tumor assessment (± 4 days) (Table 2, Table 3, and 
Table 4). CA-125 should be assessed by the same laboratory throughout the study.  
8.15. 
Quality of Life Questionnaires 
Quality of life (QOL) questionnaires EORTC QLQ-C30, EORTC QLQ-OV28, EQ-5D-5L, and 
PGIS (Greimel 2003, Osoba 1994) will be used in this trial. The questionnaires should be given 
to the patient and completed during their Screening visit and at other times specified in the 
Schedule of Assessments (Table 2, Table 3, and Table 4). At visits where administered, the 
questionnaires should be completed before other procedures at the beginning of clinic visit. The 
patient should not be sent home with the questionnaires to complete and return at their next visit.  
QOL questionnaires assessments are to continue to be administered for patients in response 
follow-up. Assessment will occur at the time of tumor assessments approximately every 12 
weeks (± 3 weeks) until documentation of PD or the start of new anticancer therapy. 
The EORTC QLQ-OV28 abdominal/GI subscale at week 8/9 is a key secondary endpoint, and 
thus this time point is the most critical, in addition to screening. 
All questionnaires should be provided in the patient’s local language at the beginning of the 
study visit before any interaction with the study Investigator, including procedures and 
treatments, and receipt of results from any tests to avoid bias to patient’s response to the study 
questionnaire. Patients should be given sufficient space and time to complete all study 
questionnaires at each visit and should be encouraged to complete any missing responses.  
8.16. 
Health-care Resource Utilization 
Resource Utilization Data will be collected on the following healthcare resources: 
hospitalizations, unscheduled office visits, and admission to hospice care or nursing home 
facility. 


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9. 
ASSESSMENT OF SAFETY 
9.1. 
Recording Adverse Events and Serious Adverse Events 
Adverse events (AEs), 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. 
Only AEs/SAEs which are considered related to a study procedure (ie blood draw or fresh tumor 
biopsy) will be captured during the pre-screening period, ie from the time of signing of the pre-
screening informed consent (if one is utilized) until the time of signing of the main study 
informed consent, or until the patient is determined to be a screen failure. All AEs and SAEs, 
regardless of causality, will be captured after the main study ICF has been signed. 
In patients receiving MIRV, all ocular AEs will be followed until resolution, stabilization, or 
return to baseline. 
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 Investigator should follow and provide updates for all AEs until clinical recovery is 
complete, laboratory values return to normal, the patient stabilizes, or death occurs, to ensure the 
safety of the patients. 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 (AE) 
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. AEs include: 
• Worsening (change in nature, severity, or frequency) of conditions present at the 
onset of the study 
• Intercurrent illnesses 
• Drug interactions 
• Events related to or possibly related to concomitant medications 
• Abnormal laboratory values (this includes significant shifts from baseline within the 
range of normal that the Investigator considers to be clinically important) 
• Clinically significant abnormalities in PE, vital signs, and weight 


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Note that PD should not be reported as an AE unless it is considered to be drug-related by the 
Investigator. 
All AEs, including AEs attributed to study procedures, occurring from the time of study 
informed consent until 30 days after last study treatment must be reported on the AE eCRF, 
regardless of the severity or relationship to study drug. Only AEs which are considered related to 
a study procedure (ie blood draw or fresh tumor biopsy) will be captured during the pre-
screening period, ie from the time of signing the pre-screening consent (if one is utilized) until 
the signing of the main study informed consent, or until the patient is determined to be a screen 
failure. The Investigator should treat patients with AEs appropriately and observe them at 
suitable intervals until the events stabilize, return to baseline or resolve. AEs 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 also 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, cause study drug discontinuation or 
constitutes in and of itself an SAE, or require therapy, 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 
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 (SAE) 
A 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 
• 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, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization 
Note that hospitalization is defined as 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, 


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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, etc). 
9.1.1.3. 
Adverse Events of Special Interest 
There are no AEs of special interest (serious or nonserious) associated with MIRV.  
9.1.2. 
Classification of Adverse Events 
All AEs will be evaluated according to the NCI CTCAE v5.0 (effective 27 November 2017). If 
the AE is not listed in the CTCAE v5.0, it should be graded based on the description given in 
Table 22. 
Table 22: 
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 medication is to be determined by the Investigator based 
on the definitions in Table 23. 


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Table 23: 
Adverse Event Causal Relatedness 
Relationship to Product(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 which 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 of study 
drug. 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 should be clinically 
plausible. The event must be definitive pharmacologically or 
phenomenologically, using a satisfactory re-challenge procedure if 
necessary.  
9.2. 
Adverse Events 
9.2.1. 
Reporting Serious Adverse Events 
Any SAE, regardless of relationship to study medication, which occurs in a patient from the time 
of study informed consent until 30 days after the last study treatment, must be recorded by the 
clinical site on an SAE report form. Only SAEs which are considered related to a study 
procedure (ie blood draw or fresh tumor biopsy) will be captured during the pre-screening 
period, ie from the time of signing the pre-screening consent (if one is utilized) until the signing 
of the main study informed consent, or until the patient is determined to be a screen failure. The 
SAE must also be recorded on the patient’s AE eCRF, including the Investigator’s assessment 
regarding the relationship of the SAE to the study drug (MIRV, Pac, PLD, or Topo). The 
Investigator will promptly supply all information requested by the Sponsor (or contract research 
organization [CRO]) regarding the SAE.  


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The Investigator must submit the SAE Report Form to ImmunoGen Pharmacovigilance (or 
designee). This form must be completed and submitted within 24 hours of the Investigator’s 
learning of the event using the contact information printed on the SAE form and contained 
within the SAE form completion instructions. Follow-up information must also be submitted 
using a new SAE Report Form. 
When reporting SAEs, the following additional points should be noted:  
• 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 reported as an SAE, but rather be recorded as 
an outcome of a specific SAE term. Initially, the event term of “death” can be used 
until the actual cause of death is known. If an autopsy was performed, the autopsy 
report should be provided. 
It is the responsibility of the Sponsor to ensure that each Investigator receives a copy of any 
suspected unexpected serious adverse reaction (SUSAR) report (CIOMS/MedWatch) regarding 
the study drug and that the report is submitted to the appropriate national regulatory agencies.  
The Investigator (or Sponsor or contracted designee) must promptly report all SUSARs to the 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) for review in accordance 
with national regulations. IRB/IEC notification of the SUSAR may take the form of 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 IRB/IEC should be retained in the site’s study 
files.  
In addition to CIOMS/MedWatch reports, the Sponsor will also notify (through annual updates 
to the IB) the Investigators and IRBs/IECs of all deaths that occur during the study, irrespective 
of relationship to study medication. 
9.2.1.1. 
Reporting of Disease Progression 
Disease progression is an anticipated occurrence in oncology drug development and is not an AE 
unto itself.  
Progression of disease should not be reported as an SAE term; any serious medical 
event/condition that results from progression of underlying disease, if untoward, should be 
reported as the SAE.  
Progression of disease with a fatal outcome does not need to be reported as an AE term. The 
applicable protocol CRF page(s) pertaining to death should be appropriately completed however, 
as disease progression. 
9.2.2. 
Reporting a Pregnancy 
Pregnancy and lactation are exclusion criteria. Women of child bearing 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 


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time in the preceding 12 consecutive months) must agree to use highly effective contraceptive 
methods (as defined in Section 5.9.6) while on study drug and for at least 3 months after the last 
dose of MIRV and for at least 6 months after the last dose of IC Chemo (Pac, PLD, and Topo). 
In addition, it is recommended that patients undergo monthly pregnancy tests for at least 
3 months after the last dose of MIRV. 
The Sponsor must be immediately notified in the event of a pregnancy occurring during the 
study and through 30 days after a patient’s last dose of study drug. 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 and submitted according to the contact 
information on the form and in the 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, would require that a study SAE 
form also be completed/submitted. 
10. 
STUDY ACTIVITIES 
All study visits and assessments that must be performed during the study and follow-up are 
included in Table 2, Table 3, and Table 4. 
10.1. 
Screening Visit 
The Investigator is responsible for keeping a record of all patients screened for entry into the 
study, including those who are subsequently excluded. The reason(s) for exclusion must be 
recorded.  
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 if performed within the screening window. These include 
radiologic tumor assessment, PEs, hematology results, serum chemistry results, coagulation 
results, urinalysis, or other assessments which may be considered part of 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.  
Note that safety blood tests, and PE do not need to be repeated if normal and conducted within 4 
days prior to C1D1. 
10.2. 
End of Treatment Visit 
Patients may voluntarily withdraw from the study drug at any time for any reason, and without 
prejudice to further treatment. In addition, patients may be withdrawn by the Investigator if they 
do not feel the patient is deriving clinical benefit or because the patient is experiencing 
unacceptable toxicity. The reasons for which a patient may be prematurely discontinued are 
listed in Section 5.6.2.2, Section 5.6.3.2, and Section 5.6.4.3. 


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Patients who withdraw or are removed from the study treatment will have an EOT visit within 7 
days of the decision to discontinue study drug.  
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 last dose of study drug.  
In some cases, nonserious AE observations may continue beyond the safety visit. All ocular AEs 
will be followed until resolution, stabilization, or return to baseline. In these instances, additional 
information may be requested by ImmunoGen to adequately categorize the nature of the toxicity. 
All serious adverse events will be followed until they resolve, stabilize or return to baseline, 
regardless of time from last dose or last visit. 
10.3.2. 
Response Follow-up 
Patients who discontinued study treatment for reasons other than PD will continue with tumor 
assessments until documentation of PD or the start of a new anticancer therapy, whichever 
comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments should occur every 6 weeks (± 
1 week) as allowed by local requirements but must occur at an interval of no more than 12 
weeks. After Week 36, assessment will occur every 12 weeks (± 3 weeks) until documentation of 
PD or the start of new anticancer therapy. Additional survival follow-up calls may occur 
periodically if needed. 
10.3.3. 
PFS2 and Survival Follow-up 
All patients who discontinue study treatment for any reason will be followed for survival after 
disease progression as per Investigator, or after start of anticancer therapy. All patients will be 
followed for survival every 3 months (± 1 month) until death, lost to follow-up, withdrawal of 
consent for survival follow-up or until EOS, whichever comes first. Additional survival follow-
up calls may occur periodically if needed. 
For the purposes of evaluating PFS2, information related to subsequent anticancer therapies and 
disease progression during survival follow-up will be collected. 
11. 
STATISTICAL METHODS 
This is a Phase 3 study designed to evaluate the efficacy of MIRV compared with that of 
standard of care IC Chemo in patients with in high FRα expressing, platinum-resistant, advanced 
high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers. 
All randomized patients will comprise the intent-to-treat (ITT) population. Efficacy will be 
evaluated using the ITT population. Safety will be evaluated in the population of randomized 
patients who have received at least one dose of study drug. 


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All statistical analyses will be performed using the most recently released SAS statistical 
software, unless otherwise noted. For categorical variables, the number (n) and percent of each 
category within a parameter will be presented. For continuous variables, the sample size (n), 
mean, median, and standard deviation, as well as 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. 
A SAP will fully describe the planned analyses for this trial and will be finalized prior to 
database lock. The safety analyses will be based on patients who receive at least one dose of 
MIRV or IC Chemo.  
11.1. 
Sample Size 
Primary endpoint is PFS per Investigator assessment. The study is designed to test the null 
hypothesis that the survival function for PFS is the same between the MIRV arm and the IC 
Chemo arm vs. the alternative hypothesis that the survival function of PFS is different between 
MIRV and IC Chemo arm. Approximately 430 patients will be randomized 1:1 (approximately 
215 patients each in the MIRV and IC Chemo arms, respectively) over a period of approximately 
18 months. The final analysis of PFS will be conducted when at least 330 events have occurred. 
The study will have 90% power to detect a PFS HR of 0.7. An interim futility analysis for PFS 
will be conducted when at least 110 events have occurred. The study may stop if the observed 
HR for PFS at the futility interim analysis is > 1. No alpha-spending is needed for this futility 
only analysis. 
The final analysis of OS will be conducted when at least 300 events have occurred. There will be 
one interim analysis (IA) for OS at the time of final analysis of PFS, at which time 
approximately 200 (60%) deaths will have been observed. A Lan-DeMets alpha-spending 
function using an O’Brien-Fleming stopping boundary will be used to control overall type I error 
for OS at 2-sided alpha level of 0.05. The study will have 90% power to detect an OS HR of 
0.6857.  
Only if the primary endpoint of PFS is statistically significant, a hierarchical testing procedure 
will be used to control the study-wise error rate (SWER) for key secondary endpoints of ORR, 
OS, and the primary PRO, in that order. 
Sample size and power was determined using R gsDesign and gsSurv packages with the 
following assumptions: 
• Median PFS for the IC Chemo arm is 3.5 months  
• Median PFS for the MIRV arm is 5 months 
• Overall attrition rate for PFS event is 13% 
• Median OS for the IC Chemo arm is 12 months 
• Median OS for the MIRV arm is 17.5 months 


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11.2. 
Stratification 
Randomization will be stratified by: 
• Number of prior lines of therapy (1 vs. 2 vs. 3) 
• IC Chemo (Pac vs. PLD vs. Topo) 
Since the type of IC Chemo received is one of the stratification factors, it is required that the 
choice of the chemotherapy agent (Pac, PLD, or Topo) be made prior to randomization.  
11.3. 
Pharmacokinetic Analyses 
PK parameters will not be calculated due to the sparse sampling scheme in this study. Summary 
statistics of the concentration at each time point (nominal time) will be presented. Graphical 
presentation of the data may also be completed using nominal time.  
11.4. 
Safety Analyses 
Safety analyses will be based on patients who receive at least one dose of MIRV or IC Chemo. 
Adverse events and concomitant medication will be listed.  
Adverse events will be coded using the latest Medical Dictionary for Regulatory Activities 
(MedDRA) version and summarized per system organ class (SOC) and preferred term (PT). 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
(WHO-DD; 01 September 2019 or later version). A dictionary listing of all unique concomitant 
medications used in the study will be provided. 
All hematology, blood chemistry, and vital signs will be listed per patient for each assessment 
and descriptive statistics will be tabulated for select criteria. Changes from baseline in 
hematology, blood chemistry, and vital signs 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 ADA.  
11.5. 
Efficacy 
Unless stated otherwise in the SAP, efficacy analyses will be performed on the ITT population. 
The ITT population is defined as all randomized patients. 
11.5.1. 
Primary Efficacy Analysis 
11.5.1.1. Progression-Free Survival 
Primary endpoint is PFS per Investigator assessment. The study is designed to test the null 
hypothesis that the survival function for PFS is the same between the MIRV arm and the IC 
Chemo arm vs. the alternative hypothesis that the survival function of PFS is different between 
MIRV and the IC Chemo arm.  
The final analysis of PFS will be conducted when at least 330 events have occurred. The study 
will have 90% power to detect a PFS HR of 0.7. An interim futility analysis for PFS will be 


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conducted when at least 110 events have occurred. The study may stop if the observed HR for 
PFS at the futility IA is > 1. No alpha-spending is needed for this futility only analysis. 
The primary endpoint of Investigator-assessed PFS, will be estimated using Kaplan-Meier 
method. Comparison between treatment arms will be conducted using Cox proportional hazard 
regression and log rank test.  
The null hypothesis is: 
• H0: the survival function for PFS is the same between MIRV arm and IC Chemo arm  
And the alternative hypothesis is: 
• Ha: the survival function for PFS is different between MIRV arm and IC Chemo arm  
The primary endpoint of PFS will be tested using stratified log-rank test (stratified by the 
stratification factors used in randomization).  
11.5.2. 
Secondary Efficacy Endpoints 
11.5.2.1. Objective Response Rate 
Objective response includes best response of CR or PR. 
The secondary endpoint of ORR (objective response = CR + PR) will be estimated along with a 
95% CI. The ORR of the MIRV arm and that of the IC Chemo arm will be compared using the 
Stratified Cochran-Mantel-Haenszel (CMH) test for treatment comparison and Clopper-Pearson 
method for 95% CI estimation.  
11.5.2.2. Overall Survival 
The secondary endpoints of OS, DOR, and PFS (as assessed by the Investigator) will be 
estimated using Kaplan-Meier method for survival function estimate. Comparison between 
treatment arms will be conducted using Cox proportional hazard regression and log rank test and 
a stratified log-rank test for hypothesis testing. 
The final analysis of OS will be conducted when at least 300 events have occurred. There will be 
one IA for OS at the time of final analysis of PFS, at which time approximately 200 (60%) 
deaths will have been observed. A Lan-DeMets alpha-spending function using an O’Brien-
Fleming stopping boundary will be used to control overall type I error for OS at 2-sided alpha 
level of 0.05. The study will have 90% power to detect an OS HR of 0.6857.  
11.5.2.3. Patient Reported Outcomes 
The abdominal/GI scale of EORTC QLQ-OV28 PRO will be a key secondary endpoint and will 
include the number of patients achieving at least a 15 point absolute improvement at Week 8/9 
assessment.  
11.6. 
Interim Analysis 
Two IAs will be conducted during the study.  


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The first interim analysis is futility only and will be conducted when at least 110 PFS events 
have occurred. The study may stop for futility if the observed PFS HR is > 1. This IA applies to 
PFS only. 
The second IA will be conducted at the final analysis of PFS when at least 330 PFS events have 
occurred. This IA applies to OS only and will be the first interim look of OS. A Lan-DeMets 
alpha-spending function using an O’Brien-Fleming stopping boundary is used to control overall 
type I error for OS at 2-sided alpha level of 0.05. It is projected that approximately 200 deaths 
will have occurred at this IA. 
The final analysis of OS will be conducted when at least 300 deaths have occurred. It is projected 
that the final analysis for OS will be approximately 1 year after the final analysis of PFS. 
If the primary endpoint of PFS is statistically significant and preliminary data suggest that 300 
deaths will not occur within 1 year after the final analysis of PFS, another IA of OS may be 
conducted 1 year after the final analysis of PFS and the stopping boundary will be adjusted 
according to the prespecified alpha-spending method. 
11.7. 
Patient-reported Outcomes 
The EORTC QLQ-C30, EORTC QLQ-OV28, EQ-5D-5L, and PGIS questionnaires will be used 
to collect data on the patient’s functioning, health-related QOL, disease symptoms and health 
status. 
The primary PRO endpoint is the number of patients achieving at least a 15% ( ≥ 15-point) 
absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at the 
Week 8/9 assessment (Stockler 2014). Patients with missing week 8/9 questionnaires will be 
excluded from analysis unless they have PD or death prior to week 8/9 assessment in which case 
they will be included as unimproved.  
Results will be summarized and presented by each treatment arm. Comparison between the two 
treatment arms will be carried out using appropriate statistical tests. Details of the analysis 
methods for PRO endpoints will be described in a PRO Statistical Analysis Plan. 
11.8. 
Multiple Comparisons 
11.8.1. 
Multiple Comparisons for Primary Efficacy Endpoint 
No multiple comparisons are needed for a single primary efficacy endpoint. 
11.8.2. 
Multiple Comparisons for Key Secondary Efficacy Endpoints 
If the primary endpoint of PFS is statistically significant at 2-sided alpha level of 0.05, the 
hierarchical testing procedure will be used to test the key secondary endpoints in the following 
order at 2-sided alpha level of 0.05 to control the study-wise type I error.  
• ORR per RECIST 1.1 criteria as assessed by the Investigator 
• OS (time from randomization to death from any cause) 
• Primary PRO endpoint of abdominal/GI Symptom Scale of EORTC QLQ-OV28 


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12. 
QUALITY CONTROL AND ASSURANCE 
12.1. 
Recording of Data and Data Quality Assurance 
Data will be documented in various source documents (eg, the patient medical chart) and then 
manually entered into the clinical trial database by study site personnel. Clinical sites will be 
monitored by ImmunoGen or its designee to ensure the accuracy of data against source 
documents. If necessary, the study site will be contacted for corrections or clarifications. 
Adverse events will be coded using the latest MedDRA version. Concomitant medications will 
be coded using the (WHO-DD; 01 September 2019 or later version. Training will occur at an 
Investigator meeting or at the site initiation visit or both, Remote web-based training may be 
provided. Instruction (eg, laboratory manuals and pharmacy manuals) will be provided to aid 
consistency in data collection and reporting across sites. 
This clinical study will be conducted according to ICH-GCP E6(R2) guidelines. Quality 
oversight shall be maintained through proactive and continual risk assessment and mitigation at 
the operational level. GCP quality assurance audits will be conducted as needed as continued 
compliance oversight.  
13. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
13.1. 
Ethical and Regulatory 
This clinical study will be conducted by the Sponsor, the Investigator, delegated Investigator 
staff and sub-Investigator(s), in accordance with the protocol, the Declaration of Helsinki, the 
International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good 
Clinical Practice (GCP), and all applicable local regulatory requirements. 
This clinical study will be recorded in a free, publicly accessible, internet-based registry, no later 
than 21 days after the first patient enrollment, in compliance with applicable regulatory 
requirements and with ImmunoGen public disclosure commitments. 
13.1.1. 
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 main study ICF and the pre-screening ICF (latter 
ICF is applicable for sites requesting permission to pre-screen for FRα positivity (high FRα) 
before performing any additional study related tests). This approval must refer to the ICF(s) and 
to the study title, study number, and version and date of issue of the study protocol, as given by 
the Sponsor on the cover page of the protocol. 
Status reports must be submitted to the IRB/IEC at least once per year or as per institutional 
guidelines. The IRB/IEC must be notified of completion of the study 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 


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made to the IRB/IEC, including a list of all reports and documents submitted. AEs, which are 
subject to expedited reporting to the FDA or other regulatory agencies (SUSARs), must be 
submitted promptly to the IRB/IEC. 
13.1.2. 
Patient Information and Consent 
An ICF that includes information about the study will be prepared and given to the patient, or the 
patient’s legally authorized representative(s). The ICF will contain all FDA and ICH-required 
elements and be approved by an IRB/IEC. The ICF must be in a language understandable to the 
patient or the patient’s legally authorized representative(s). Before enrolling in the clinical study, 
the nature, scope, and possible consequences of the clinical study will be explained to the patient 
or the patient’s legally authorized representative(s) in a form understandable to him or her. After 
the patient or the patient’s legally authorized representative(s) has been given ample time to read 
and ask questions regarding the ICF 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 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. The informed consent process must be recorded and dated in the 
patient’s source document. 
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 13.3. 
The Investigator must not undertake any measures specifically required solely for the clinical 
study until valid informed consent has been obtained. 
A model of the pre-screening and the main study ICF will be provided to the sites separately for 
this protocol. The main study consent can be used to confirm a patient’s consent to all study 
procedures and all study-specific screening tests. The pre-screening ICF can be used to pre-
screen patients for FRα status before performing any additional study related tests, as well as 
collect a blood sample for Soluble FRα. If a patient is eligible based on FRα expression level, the 
patient will be provided the main study consent and only after signing the main study ICF will 
additional study-specific screening tests be performed. Alternatively, the patient can be 
consented on both pre-screening and main study ICF at the same time; and FRα testing and 
study-specific screening assessments can be carried out in parallel.  
Patients must be consented to the most current version of the ICF during their participation in the 
study.  
13.2. 
Investigators and Study Administrative Structure 
Before initiation of the study, the Investigators at US sites must provide the Sponsor with a 
completed Form FDA 1572 or equivalent form. Study medications must be administered only 


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under the supervision of the Investigators listed on this form. Curriculum vitae must be provided 
for the Investigators and sub-investigators listed on Form FDA 1572 or equivalent form. 
The Investigator must ensure that all persons assisting with the study are adequately informed 
about the protocol, any amendments to the protocol, the study treatments, and their study related 
duties and functions. The Investigator must maintain a list of sub-investigators and other 
appropriately qualified persons to whom he or she has delegated significant study related duties. 
13.3. 
Patient Confidentiality 
Patient names will not be supplied to the Sponsor. If the patient name appears on any documents, 
it must be redacted before a copy of the document is supplied to the Sponsor. Study findings 
stored on a computer will be stored in accordance with local data protection laws. Patient blood 
and tissue samples, and radiographic images sent to outside laboratories and/or CROs are 
identified by study patient number only to ensure maintenance of confidentiality. The patient 
consent form will state publications resulting from this study will not refer to patient name or 
include any other information that might disclose the identity of the patient. The patients will be 
told that representatives of the Sponsor, a designated CRO, the IRB/IEC, or regulatory 
authorities may inspect their medical records to verify the information collected, and that all 
personal information made available for 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. 
13.4. 
Study Monitoring 
Sponsor or its designee will monitor the conduct of the trial on a regular basis throughout the 
duration of the study, according to the monitoring plan and in compliance with ICH-GCP 
E6(R2). Monitoring of the study will serve to ensure: (a) The rights and well-being of human 
subjects are protected; (b) The reported trial data are accurate, complete, and verifiable from 
source documentation; and (c) The conduct of the trial is in compliance with the currently 
approved protocol/amendment(s), with GCP, and with applicable regulatory requirement(s). 
The study monitor will train site personnel on the conduct of the trial. The monitor will assess 
the trial site’s compliance with the protocol and will periodically review and verify a sample of 
the patient data recorded on CRFs against source documentation. The study monitor will also 
review documents that provide evidence of the proper consent and eligibility of enrolled patients, 
the compliant conduct of study procedures, the administration and disposition of investigational 
product(s), the reporting of serious adverse events and adverse reactions, and the continued 
maintenance of trial records.  
The Investigator will allocate adequate time to support such monitoring activities. The 
Investigator will also ensure that the monitor is given reasonable remote and/or on-site access to 
study-related documents, source documents (regardless of media) and study-related facilities (eg, 
investigational pharmacy, etc). Queries may be raised if any datum is unclear or contradictory. 
The Investigator and site personnel must address all queries in a timely manner. 


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13.5. 
Study Committees 
13.5.1. 
Steering Committee 
A Steering Committee (SC) will be comprised of lead Investigators from North America and 
Europe. The purpose of the SC is to provide overall guidance regarding design of the study, 
conduct and execution of the trial. This includes (but is not limited to) safety, efficacy, 
enrollment and contribution to scientific input for publications. Responsibilities of the SC and 
communication flow between the Independent Data Monitoring Committee (IDMC), SC and 
ImmunoGen will be included in the SC charter document.  
13.5.2. 
Independent Data Monitoring Committee 
An IDMC has been established for this study and specific guidelines on the operation and 
purpose of the IDMC is documented in a Charter. The committee includes at least 3 members, 
including a statistician and medical oncologists experienced in the treatment of EOC. Safety 
review meetings will be held as per the IDMC charter and as needed if any unexpected safety 
signals emerge during the study. The IDMC will be responsible for independently evaluating 
safety data of patients enrolled to the study. Decisions on study termination, amendment of the 
protocol, or cessation of patient recruitment will be made after recommendations from the IDMC 
have been assessed by the Sponsor. 
13.6. 
Case Report Forms and Study Reports 
Electronic case report forms (eCRFs) are provided for each patient. All forms must be filled out 
by authorized study personnel. The Investigator is required to sign/e-sign the eCRF after all data 
have been captured for each patient. If corrections are made after review and signature by the 
Investigator, he or she must be made aware of the changes, and his or her awareness documented 
by re-signing the eCRF. 
13.7. 
Critical Documents 
Before ImmunoGen initiates the study at a given site, it is the responsibility of the Investigator to 
ensure that the following documents are made available to ImmunoGen or their designee: 
• 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/ICF, and any other written 
information to be provided regarding patient recruitment procedures 
• Copy of IRB/IEC approved Patient Information/ICF/any other written 
information/advertisement 


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• List of IRB/IEC Committee members/constitution or equivalent compliance statement 
• Study and Financial agreement(s) 
• Completed Form FDA 1572 or equivalent form 
• 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 made 
available to ImmunoGen. 
13.8. 
Protocol Adherence 
Each Investigator must adhere to the protocol as detailed in this document and agree that any 
changes to the protocol must be approved by ImmunoGen’s authorized representative in writing 
before seeking approval, where necessary, from the IRB/IEC, Research Ethics Committee 
(REC), or Ethics Review Board (ERB). Each Investigator will be responsible for allowing only 
those patients who have met protocol eligibility criteria to be enrolled. 
Modifications to the protocol should not be made without agreement of the Investigators and 
ImmunoGen. Changes to the protocol will require written IRB/IEC, REC, or ERB 
approval/favorable opinion before implementation, except when the modification is needed to 
eliminate an immediate hazard(s) to patients. The IRB/IEC/REC/ERB 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/REC/ERB. ImmunoGen will submit all protocol 
modifications to the appropriate regulatory authorities in accordance with the governing 
regulations. 
When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to 
patients, the Investigator will contact ImmunoGen, if circumstances permit, to discuss the 
planned course of action. Any departures from the protocol must be fully documented in the 
source documentation. 
Prospective waivers or exemptions are not permitted.  
13.9. 
End of Study 
EOS will occur after the final analysis of OS, which will be conducted when at least 300 deaths 
have occurred. It is projected that the final analysis for OS will be approximately 1 year after the 
final analysis of PFS. After the final analysis of OS, the last survival follow-up visit for the last 
patient will be performed and the study will close. At the time of the final analysis for OS, if 
patients are still receiving clinical benefit from study treatment at EOS, either the study will be 
amended to allow those patients to continue to receive treatment with limited data collection (eg 
SAEs, dosing information) until they are no longer benefiting or patients will be given the option 
to roll-over to a long-term extension study.  


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13.10. 
Study Termination 
If the Sponsor, an Investigator, or Clinical Study Monitor discovers conditions arising during the 
study that indicate that the clinical investigation should be halted due to 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 study drug may be made at any time.  
Within 15 days of premature closure, ImmunoGen must notify the competent authorities and 
IECs/IRBs of any member state where the study is being conducted, providing the reasons for 
study closure. 
13.11. 
Site Termination 
If ImmunoGen, an Investigator, or regulatory authorities discover conditions during the study 
that indicate that the study or related activities at a particular center should be terminated, this 
action may be taken after appropriate consultation between ImmunoGen and the Investigator. 
Conditions that may warrant study or center termination include but are not limited to: 
• Discovery of an unexpected, serious, and/or unacceptable risk to patients enrolled in 
the study 
• Decision on the part of ImmunoGen to suspend or discontinue testing, evaluation, or 
development of the clinical program 
• Unacceptable benefit-risk relationship of the investigational product 
• Recommendations of the IDMC or regulatory body 
• Investigator failure to comply with applicable regulatory authority requirements or 
protocol requirements 
• Submission of knowingly false information from the center to ImmunoGen or 
regulatory authorities 
Study or center termination and follow-up will be performed in compliance with the conditions 
set forth in 21 CFR Section 312 and in compliance with the principles set forth in International 
Conference on Harmonisation (ICH) Good Clinical Practices (GCPs). 
13.12. 
Access to Source Documentation 
According to the ICH E6 GCP, the monitoring team must check the clinical trial database entries 
against the source documents. The ICF will include a statement by which the patient allows the 
Sponsor’s duly authorized personnel, the IRB/IEC, and the regulatory authorities to have direct 
access to original medical records which support the data in the clinical trial database (eg, 
patient's medical file, appointment books, original laboratory records, etc). These personnel, 
bound by professional secrecy, must maintain the confidentiality of all personal identity or 
personal medical information (according to confidentiality and personal data protection rules). 


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13.13. 
Audits and Inspections 
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 clinical trial database for completeness and clarity, 
crosschecking with source documents, and clarification of administrative matters will be 
performed. 
13.14. 
Data Generation and Analysis 
The clinical database will be developed and maintained by a CRO or an EDC technology 
provider as designated by ImmunoGen. ImmunoGen or its designee will be responsible for 
performing study data management activities and analyses. 
13.15. 
Retention of Data 
Essential documents will be retained until the following requirements are met: 
• a minimum of two years (or longer, if required by local/regional regulation) has 
elapsed after an approval of a marketing application , which was supported by this 
study, or  
• there are no pending or contemplated marketing applications, or 
• at least two 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 as to when these 
documents no longer need to be retained. 
13.16. 
Financial Disclosure 
The Investigator must 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 been completed. The 
appropriate form will be provided to the Investigator by the Sponsor, which will be signed and 
dated by the Investigator, before the start of the study. If financial interests change at any time 
during the study, an updated financial disclosure form is required. 
All financial details relating to the Investigators’ participation in this study are provided in the 
separate contract between the institution and ImmunoGen. 
13.17. 
Insurance Compensation 
The Sponsor certifies that it has taken out a liability insurance policy covering all clinical trials 
under its sponsorship. This insurance policy is in accordance with local laws and requirements. 


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The insurance of the Sponsor does not relieve the Investigator and the collaborators from any 
obligation to maintain their own liability insurance policy. An insurance certificate will be 
provided to the IECs/IRBs or regulatory authorities in countries requiring this document. 
13.18. 
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 as well as 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 case report forms completed as part of the study. This information may 
be disclosed to other physicians who are conducting similar studies and to the global 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 
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. 
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https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Version 2.2019 – Sep 17, 
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treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997;15(6):2183-93.  
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with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic 
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40 and 50mg/ m2 pegylated liposomal doxorubin (PLD) in recurrent epithelial ovarian cancer 
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APPENDIX A. EASTERN COOPERATIVE ONCOLOGY GROUP 
(ECOG) PERFORMANCE STATUS SCALE 
(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) 
 


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APPENDIX B. RESPONSE DEFINITIONS (RECIST 1.1) 
(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. 
• MRI 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 (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. In the event 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 < 10mm are considered non-pathological and are 
not to be recorded or followed.  
• Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pneumonitis, inflammatory breast disease, and abdominal masses 
(not followed by CT or MRI), are considered as non-measurable. 
Target Lesions: All measurable lesions up to a maximum of two lesions per organ and five 
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.  
• It may be the case that on occasion, the largest lesion does not lend itself to 
reproducible measurement in which circumstance the next largest lesion which can be 
measured reproducibly should be selected. 


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• 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 
over and above the five 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, 
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 only be considered for response assessment 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 as 
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 
lesion.  
Bone Lesions: Bone scan, PET scan or 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 
or MRI can be considered as measurable lesions if the soft tissue component meets 
the definition of measurability described above. 
• Blastic bone lesions are non-measurable. 
Lesions with Prior Local Treatment: Lesions situated in a previously irradiated area, or in an 
area subjected to other locoregional 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 
or MRI scans performed after the completion of radiation, or  
• 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 


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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 or MRI: This guideline has defined measurability of lesions on CT scan 
based on the assumption that CT 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. MRI is 
also acceptable in certain situations (eg, for body scan) except for lung.  
CA-125: Tumor marker CA-125 alone cannot be used to assess response or determine 
progression; however, it will be followed. CA-125 measurements will be performed as indicated 
in Table 2, Table 3, and Table 4. Patients whose CA-125 is above the upper normal limit at 
baseline will need to have their values normalize to ≤ upper normal limit, in addition to complete 
disappearance of measurable or evaluable disease, to be considered in complete response. 
Other methods of assessment, PET-CT, ultrasound and FDG-PET should not be used for 
response assessment in this study. 
Time Point Assessments 
Patients will have tumor measurements performed within 28 days before first dose of study drug 
and every 6 weeks (±1 week) from C1D1 for the first 36 weeks on study and every 12 weeks (± 
3 weeks) thereafter. 
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, 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). 
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).  


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Non-target lesions are to be assessed qualitatively (present, resolved, or unequivocal 
progression) and new lesion, 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 < 10mm.  
Partial Response (PR) 
At least 30% decrease in the sum of diameters (SoD of target lesions, taking 
as reference the baseline SoD 
Progressive Disease 
(PD) 
At least a 20% increase in the SoD of target lesion, taken as reference the 
smallest (nadir) SoD since and including baseline. In addition to the relative 
increase of 20%, the SoD 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 (N/A) 
No target lesions identified at baseline 
Unable to Evaluate 
(UE) 
One or more target lesions are not imaged and the remainder of the SoD 
compared with the nadir SoD 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 SoD 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 upper normal limit. 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 CA-
125 above the normal limits if CA-125 at baseline is above the upper 
normal limit 
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 (N/A) 
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 
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 SoD is 0 (ie, the patient had a prior target lesion CR), the re-appearance of any prior target 
lesions to any degree constitutes PD. 


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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 non assessed or incompletely assessed for new lesion 
Determining Overall TPR 
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 
CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; UE, unable 
to evaluate; NA, not applicable (no such lesions at Screening); Any, CR, PR, SD, PD, NA or UE. 
The overall response at a given time point does not depend upon the overall response assigned at any 
prior time point. 
*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. 
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 a given time point, 
changes in tumor measurements must be confirmed by repeat assessments that should be 
performed no less 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. 


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APPENDIX C. GYNECOLOGIC CANCER INTERGROUP (GCIG) 
CRITERIA FOR EVALUATION OF CA-125 
(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 
trials so that response can be measured by either RECIST or CA-125 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: 
•  ≥ 50% reduction in CA-125 levels from baseline 
• the response must be confirmed and maintained for at least 28 days 
• the pretreatment sample must be ≥ 2.0 times the ULN and within two weeks before 
starting treatment 
• the date of response corresponds to the date when the CA-125 level is first reduced by 
50%  
To calculate CA-125 responses accurately, the following rules apply:  
• Intervening samples and the 28-day confirmatory sample must be less than or equal to 
(within an assay variability of 10%) the previous sample 
• Variations within the normal range of CA-125 levels will not interfere with the 
response definition.  
Evaluation of Progression 
Progression or Recurrence based on serum CA-125 levels will be defined on the basis of a 
progressive serial elevation of serum CA-125, according to the following criteria:  
a. Patients with elevated CA-125 pretreatment and normalisation of CA-125 must show 
evidence of CA-125 greater than, or equal to, two times the upper normal limit on 
two occasions at least one week apart, or  
b. Patients with elevated CA-125 pretreatment, which never normalises must show 
evidence of CA-125 greater than, or equal to, two times the nadir value on two 
occasions at least one week apart, or  
c. Patients with CA-125 in the normal range pretreatment must show evidence of 
CA125 greater than, or equal to, two times the upper normal limit on two occasions at 
least one week apart.  
Elevated values must be confirmed by two separate measurements obtained at least one week 
apart. CA-125 progression will be assigned the date of the first measurement that meets the 
criteria as noted. Patients are not evaluable by CA-125 if they have received mouse antibodies 
(unless the assay used has been shown not to be influenced by HAMA [Taylor 2005 and Rustin 
2005]) or if there has been medical and/or surgical interference with their peritoneum or pleura 
during the previous 28 days.  


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A patient may be declared to have progressive disease on the basis of either the objective 
RECIST criteria or the CA-125 criteria. The date of progression will be the date of the earlier of 
the two events if both are documented. 
Definition of progression after first-line therapy in ovarian cancer as proposed by the 
GCIG 
GCIG 
subcategorized 
group 
RECIST Measurable/non-measurable 
disease 
 
CA-125 
A 
Compared to baseline (or lowest sum 
while on study if less than baseline), a 
20% increase in sum of longest diameters 
(RECIST definition) 
or 
Any new lesions (measurable or non-
measurable) 
Date PD: date of documentation of 
increase or new lesions 
 
 
 
 
A
N
D 
/ 
O
R 
CA-125 ≥ 2 x ULN 
documented on two 
occasions # 
Date of PD: first date of 
the CA-125 elevation to ≥ 
2x nadir value 
 
B 
As for A 
CA-125 ≥ 2 x nadir value 
on two occasions # 
Date of PD: first date of 
the CA-125 elevation to ≥ 
2x nadir value 
B 
As for A 
As for A 
GCIG groups A, B & C defined above.  
# Repeat CA-125 any time, but normally not less than 1 week after the first elevated CA-125 level. CA-125 levels 
sampled after patients received mouse antibodies (unless the assay used has been shown not to be influenced by 
HAMAa,b) or if there has been medical and/or surgical interference with their peritoneum or pleura during the 
previous 28 days, should not be taken into account. 
a Taylor PT, Haverstick D. J Natl Cancer Inst 2005, 97:151, Re: new guidelines to evaluate the response to 
treatment in solid tumors [ovarian cancer].  
b Rustin GJS. J Natl Cancer Inst 2005, 97:152, Re: new guidelines to evaluate the response to treatment in solid 
tumors [ovarian cancer]. 
Timing of CA-125 assessments: 
The GCIG recommends that CA-125 measurements be taken at specific time intervals.  
• The first sample would be collected within two weeks before treatment is started 
• CA-125 measurements will be performed as indicated in Table 2, Table 3, and 
Table 4.  


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• 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 CA-125 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 CA-125 response definition has been produced to evaluate relapse therapy. If assessing 
therapy that includes two treatment modalities for relapse (eg, surgery and chemotherapy), any 
CA-125 response results from both treatments. CA-125 cannot distinguish between the effects of 
each treatment. To calculate response rates in protocols, an ITT analysis should be used that 
includes all patients with an initial CA-125 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 CA-125 response and whose CA-125 level falls to within the normal 
range.  


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APPENDIX D. LIST OF CONCOMITANT MEDICATIONS REQUIRING 
CAREFUL MONITORING 
CYP Enzymes 
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 
Ref: FDA drug development resources: 
(http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm09366
4.htm#classSub) 


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APPENDIX E. ADJUSTED IDEAL BODY WEIGHT (AIBW) 
CALCULATION 
 
Adjusted Ideal Body Weight (AIBW) 
AIBW = IBW1 + 0.4 (Actual weight – IBW1) 
 
Ideal Body Weight (IBW) 
IBW1 (female) = 0.9H1-92 
 
(1H=height in cm; W=weight in kg) 

SAP_001.pdf: 
 
 
 
 
 
ImmunoGen, Inc. 
Protocol #: IMGN853-0416 
 
MIRASOL: A Randomized, Open-label, Phase 3 Study of Mirvetuximab 
Soravtansine vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, 
Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube 
Cancers with High Folate Receptor-Alpha Expression 
 
Statistical Analysis Plan 
 
Version 3.0 
14 February 2023 
 
 
 
 
 
 
 
 
Prepared by: 
 
Director, Biostatistics 
ImmunoGen, Inc. 
 
 
 


Statistical Analysis Plan for Protocol: IMGN853-0416 
 
 
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SPONSOR SIGNATURE PAGE 
 
 
 
 
 
 
Director Biostatistics 
ImmunoGen, Inc. 
 
 
Date 
 
 
 
 
 
 
Executive Medical Director  
ImmunoGen, Inc. 
 
 
 
 
 
 
Date 
 
 
VP Biometrics 
ImmunoGen, Inc. 
 
 
Date 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ........................................................................................................9 
1.1. 
Background ...................................................................................................................9 
2. 
STUDY DESIGN .........................................................................................................9 
2.1. 
Protocol Objectives .......................................................................................................9 
2.1.1. 
Primary Objective .........................................................................................................9 
2.1.2. 
Secondary Objectives ...................................................................................................9 
2.1.2.1. 
Key Secondary Objectives: ...........................................................................................9 
2.1.2.2. 
Other Secondary Objectives: ......................................................................................10 
2.1.2.3. 
Exploratory Objectives ...............................................................................................10 
2.1.3. 
Study Endpoints ..........................................................................................................10 
2.1.3.1. 
Primary Endpoint ........................................................................................................10 
2.1.3.2. 
Secondary Endpoints ..................................................................................................10 
2.1.3.3. 
Exploratory Endpoints ................................................................................................11 
2.2. 
Study Overview ..........................................................................................................11 
2.2.1. 
Study Population .........................................................................................................13 
2.2.2. 
Power and Sample Size ..............................................................................................13 
2.2.2.1. 
Primary Endpoint ........................................................................................................13 
2.2.2.2. 
Power for Key Secondary Endpoints ..........................................................................14 
2.2.3. 
Treatment Randomization and Stratification ..............................................................15 
2.2.4. 
Blinding and the BICR ...............................................................................................15 
2.2.4.1. 
BICR ...........................................................................................................................15 
2.2.5. 
Assessment Schedule ..................................................................................................15 
2.3. 
Interventions ...............................................................................................................15 
2.3.1. 
Clinical Trial Material ................................................................................................15 
3. 
GENERAL ANALYTICAL CONSIDERATIONS ...................................................16 
3.1. 
Data Sources ...............................................................................................................16 
3.2. 
Definition of Baseline .................................................................................................16 
3.3. 
Missing Data ...............................................................................................................16 
3.4. 
Multiple Assessments for the Same Assessment Time Point .....................................18 
3.5. 
Multiple Study Centers ...............................................................................................18 


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3.6. 
Covariate Adjustment in Primary Analysis ................................................................18 
3.7. 
Sample Size Reassessment .........................................................................................18 
3.8. 
Interim Analyses .........................................................................................................18 
3.9. 
Timing of Final Analysis ............................................................................................19 
3.10. 
Hypothesis Testing and Multiple Comparisons ..........................................................19 
3.10.1. 
Primary Endpoint ........................................................................................................19 
3.10.2. 
Key Secondary Endpoints ...........................................................................................19 
3.11. 
Analysis Populations ..................................................................................................20 
3.11.1. 
Screened ......................................................................................................................20 
3.11.2. 
ITT Population ............................................................................................................20 
3.11.3. 
Per Protocol Population ..............................................................................................21 
3.11.4. 
Response-Evaluable Population .................................................................................21 
3.11.5. 
CA-125-Evaluable Population ....................................................................................21 
3.11.6. 
Safety Population ........................................................................................................21 
3.11.7. 
Pharmacokinetic (PK) Analysis Population ...............................................................21 
3.11.8. 
Longitudinal Period Population (LPP) .......................................................................22 
3.12. 
Data Display Characteristics .......................................................................................22 
4. 
PATIENT ACCOUNTABILITY ...............................................................................22 
4.1. 
Patient Characteristics ................................................................................................22 
4.1.1. 
Demography ...............................................................................................................22 
4.1.2. 
Height and Baseline Weight, AIBW, and Body Surface Area ...................................23 
4.1.3. 
Medical History ..........................................................................................................23 
4.1.4. 
Disease Characteristics, Prior Therapy, and Gene Mutations ....................................23 
4.2. 
Patient Disposition ......................................................................................................24 
4.2.1. 
Screened and Enrolled Patients ..................................................................................24 
4.2.2. 
ITT, Safety Disposition ..............................................................................................24 
4.2.3. 
Protocol Deviations and Population Inclusions ..........................................................24 
5. 
EFFICACY ANALYSES ...........................................................................................24 
5.1. 
Efficacy Outcomes ......................................................................................................25 
5.1.1. 
PFS ..............................................................................................................................25 
5.1.2. 
Best Overall Response ................................................................................................25 
5.1.2.1. 
ORR ............................................................................................................................26 


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5.1.2.2. 
DOR ............................................................................................................................26 
5.1.2.3. 
Time to Response .......................................................................................................26 
5.1.3. 
OS ...............................................................................................................................26 
5.1.4. 
CA-125 Response .......................................................................................................26 
5.1.5. 
RECIST-Related Endpoints –Investigator’s or BICR Assessment ............................26 
5.1.6. 
PFS2 ............................................................................................................................27 
5.2. 
Primary Efficacy Outcome Analysis ..........................................................................27 
5.3. 
Secondary Efficacy Analyses .....................................................................................28 
5.3.1. 
Key Secondary Efficacy Analyses ..............................................................................28 
5.3.2. 
Other Secondary Efficacy Analyses ...........................................................................29 
5.4. 
Exploratory Efficacy Analyses ...................................................................................30 
5.5. 
Efficacy Analysis on Subgroups of Patients ...............................................................31 
5.6. 
Additional Sensitivity Analyses .................................................................................31 
5.7. 
Strategies for Pooling Stratification Factors ...............................................................34 
5.8. 
Other Efficacy-related Summaries .............................................................................35 
6. 
SAFETY ANALYSES ...............................................................................................36 
6.1. 
Exposure .....................................................................................................................36 
6.2. 
AEs .............................................................................................................................36 
6.2.1. 
Fresh Biopsy Patient Adverse Events .........................................................................39 
6.2.2. 
Infusion-related Reactions ..........................................................................................39 
6.3. 
Clinical Laboratory Results ........................................................................................39 
6.4. 
Vital Signs ..................................................................................................................41 
6.5. 
ECGs ...........................................................................................................................41 
6.6. 
Concomitant Medications ...........................................................................................41 
6.7. 
Concomitant Procedures .............................................................................................42 
6.8. 
Ophthalmic Examinations ..........................................................................................43 
6.9. 
Ocular Symptom Assessments ...................................................................................43 
6.10. 
Corticosteroid and Lubricating Eye Drop Compliance ..............................................43 
6.11. 
Transfusions ................................................................................................................43 
6.12. 
ECOG PS ....................................................................................................................43 
6.13. 
ECHO/MUGA ............................................................................................................43 
7. 
PRO.............................................................................................................................43 


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8. 
IMMUNOGENICITY ................................................................................................43 
9. 
BIOMARKERS ..........................................................................................................44 
10. 
PHARMACOKINETICS ...........................................................................................44 
11. 
REVISION HISTORY ...............................................................................................44 
12. 
REFERENCES ...........................................................................................................45 
 
LIST OF TABLES 
Table 1: 
History of Protocol Amendments .................................................................................9 
Table 2: 
Dosing and Dosing Schedule for Phase 3 Portion ......................................................16 
Table 3: 
Analysis Populations ..................................................................................................20 
Table 4: 
PFS Definitions ...........................................................................................................25 
Table 5: 
PFSAINV Definitions ...................................................................................................32 
Table 6: 
PFSB INV Definitions ...................................................................................................33 
Table 7: 
PFSRINV Definitions ...................................................................................................33 
Table 8: 
Pooling of Stratification Factors .................................................................................34 
Table 9:  
Classification of Vital Signs .......................................................................................41 
Table 10: Revision History .........................................................................................................44 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................12 
Figure 2: 
Study Period Schema ..................................................................................................13 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation or 
Specialist Term  
Explanation 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
AIBW 
Adjusted ideal body weight 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BICR 
Blinded Independent Central Review 
BOR 
Best overall response 
BRCA 
Breast cancer susceptibility gene 
BSA 
Body surface area 
CA-125 
Cancer antigen 125 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel test 
CR 
Complete response 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOR 
Duration of response 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
eCRF 
Electronic case report form 
EOC 
Epithelial ovarian cancer 
EORTC 
European Organisation for Research and Treatment of Cancer 
FRα 
Folate receptor alpha 
GCIG 
Gynecologic Cancer Intergroup 
IC 
Investigator’s choice/selected standard-of-care chemotherapy 
IDMC 
Independent Data Monitoring Committee 
IMGN 
ImmunoGen 
INV 
Investigator 
IRT 
Interactive Response Technology 


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Abbreviation or 
Specialist Term  
Explanation  
ITT  
Intent-to-treat  
MedDRA  
Medical Dictionary for Regulatory Activities  
MUGA 
Multigated acquisition scan  
OR 
Overall response 
ORR  
Objective response rate  
OS  
Overall survival  
Pac 
Paclitaxel 
PD  
Progressive disease  
PFS  
Progression-free survival  
PFS2 
Time to second disease progression 
PK  
Pharmacokinetics  
PLD  
Pegylated liposomal doxorubicin  
PR  
Partial response  
PRO 
Patient reported outcomes 
PT 
Preferred term 
Q3W  
Every 3 weeks  
Q4W  
Every 4 weeks  
QoLP 
Primary endpoint for quality of life 
QT 
The length of time it takes the electrical system in the heart to repolarize, 
adjusted for heart rate 
QTc 
Corrected QT interval 
QTcF 
Corrected QT using Fridericia’s formula 
RECIST  
Response Evaluation Criteria in Solid Tumors  
RMST 
Restricted mean survival time 
SAE  
Serious adverse event  
SAP  
Statistical analysis plan  
SOC 
System organ class 
TBL 
Total bilirubin 
TEAE  
Treatment-emergent adverse event  
Topo 
Topotecan 
TTR 
Time to response 


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Abbreviation or 
Specialist Term  
Explanation  
ULN  
Upper limit of normal  
WHO Drug  
World Health Organization Drug Dictionary 
1. 
INTRODUCTION 
1.1. 
Background 
This Statistical Analysis Plan (SAP) is based on Version 2.0 of Protocol IMGN853-0416, dated 
04DEC2020.  
A brief history of protocol amendments is presented in Table 1. 
Table 1: 
History of Protocol Amendments 
Version 
Approval Date 
Salient Changes (if any)* 
Original Protocol 
10OCT2019 
N/A 
Amendment 1 
09DEC2019 
N/A 
Amendment 2 
04DEC2020 
N/A 
*Changes expected to require accommodation in analysis plan. 
This SAP will govern the analysis of study data. The plan for the primary efficacy analysis and 
all other analyses may be modified until the time of interim futility analysis. Any deviations from 
the SAP will be documented as such in the study report.  
2. 
STUDY DESIGN 
2.1. 
Protocol Objectives 
2.1.1. 
Primary Objective 
• To compare the progression-free survival (PFS) of patients randomized to 
mirvetuximab soravtansine (MIRV) versus Investigator’s Choice chemotherapy (IC 
Chemo), as assessed by the investigator, in patients with high Folate Receptor-α 
(FRα) level (≥ 75% of tumor staining at ≥ 2+ intensity). 
2.1.2. 
Secondary Objectives 
2.1.2.1. 
Key Secondary Objectives: 
• To compare the objective response rate (ORR) of patients randomized to MIRV 
versus IC Chemo, as assessed by the investigator. 
• To compare the overall survival (OS) of patients randomized to MIRV versus IC 
Chemo. 


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• To compare the primary patient-reported outcome (PRO) using the European 
Organization for Research and Treatment of Cancer (EORTC) QLQ-OV28 
(Abdominal/GI Symptom Scale) assessment from patients randomized to MIRV 
versus IC Chemo. 
2.1.2.2. 
Other Secondary Objectives: 
• To compare the safety and tolerability of MIRV vs. IC Chemo.  
• To compare the duration of response (DOR) in patients randomized to MIRV versus 
IC Chemo. 
• To compare the cancer antigen (CA-125) response rate (RR) per Gynecologic Cancer 
Intergroup (GCIG) CA-125 criteria in patients randomized to MIRV versus IC 
Chemo.  
• To compare the time to progression or death on the next line of treatment (PFS2) in 
patients randomized to MIRV versus IC Chemo. 
2.1.2.3. 
Exploratory Objectives 
• To assess patient-reported outcomes (PRO) using the EORTC QLQ-C30, EuroQol-5 
Dimension 5-level (EQ-5D-5L) and Patient Global Impression of Severity (PGIS) 
questionnaires.  
• To evaluate concentrations of MIRV, total antibody (TAb), DM4 and S-methyl DM4, 
using sparse sampling. 
• To assess the immunogenicity of MIRV via anti-drug antibodies (ADAs).  
• To evaluate potential biomarkers in blood and tumor tissue predictive of response to 
MIRV.  
2.1.3. 
Study Endpoints 
2.1.3.1. 
Primary Endpoint 
• PFS: defined as the time from date of randomization until Investigator-assessed 
progressive disease (PD) or death, whichever occurs first (PFSINV). 
2.1.3.2. 
Secondary Endpoints 
2.1.3.2.1. Key Secondary Endpoints: 
• ORR: Objective response includes best response of complete response (CR) or partial 
response (PR) as assessed by the Investigator (ORRINV). 
• OS: Overall survival defined as the time from date of randomization until the date of 
death. Patients alive at the time of analysis will be censored at the last date known to 
be alive. 


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• QoLP: Primary PRO assessment, defined as the number of patients achieving at least 
15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of 
EORTC QLQ-OV28. 
2.1.3.2.2. Other Secondary Endpoints: 
• Treatment-emergent adverse events (TEAEs) and laboratory test results, physical 
examination, or vital signs. 
• DOR: Duration of response, defined as the time from initial response until 
Investigator-assessed PD for all patients who achieve a confirmed objective response 
(PR or CR). 
• CA-125 response determined using the GCIG criteria defined in Appendix C of the 
Protocol. CA-125 response per GCIG criteria will be determined programmatically. 
• PFS2 defined as the time from date of randomization until second disease progression 
or death whichever occurs first. 
2.1.3.3. 
Exploratory Endpoints 
• PRO from EORTC QLQ-C30/OV-28, EQ5D-5L and PGIS . 
− Analyses of PRO endpoints will be covered in a separate PRO SAP. 
• Immunogenicity is defined as the presence of ADA to MIRV.  
• Soluble FRα levels: 
2.2. 
Study Overview  
This study is designed to compare the efficacy of MIRV to that of IC Chemo in women with 
platinum resistant advanced epithelial ovarian cancer (EOC), primary peritoneal cancer, or 
fallopian tube cancer.  
Patients will be stratified by the number of prior lines of treatment (1 vs 2 vs 3) and IC 
chemotherapy (paclitaxel [Pac] vs pegylated liposomal doxorubicin (PLD) vs topotecan [Topo]) 
which is chosen by the investigator prior to randomization. Patients will be randomized 1:1 into 
1 of 2 arms as follows (Figure 1):  
• Arm 1: IMGN853 6mg/kg AIBW Q3W.  
• Arm 2: IC chemotherapy (weekly paclitaxel every 4 weeks [Q4W], PLD 
administered once Q4W, or topotecan administered either on Days 1, 8, and 15 Q4W 
or for 5 consecutive days Q3W).  




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Figure 2: 
Study Period Schema 
 
EOT = end of treatment; Pac = paclitaxel; PLD = pegylated liposomal doxorubicin; Q3W = every 3 weeks; 
Topo = topotecan. 
2.2.1. 
Study Population 
All patients must have 1 of the following pathologically documented, definitively diagnosed 
tumor types: advanced platinum resistant EOC, primary peritoneal cancer, or fallopian tube 
cancer. Patients must also have the following: 
• At least 1 lesion that meets the definition of measurable disease according to RECIST 
Version 1.1 (radiologically measured by the Investigator).  
• Received at least 1 but no more than 3 prior systemic lines of anticancer therapy and 
for whom single-agent therapy is appropriate as the next line of treatment.  
• Confirmation of FRα positivity as defined by the Ventana FOLR1 (FOLR-2.1) CDx 
assay in archival or fresh biopsy tumor sample. 
See Section 3.1 of the protocol for a complete list of the inclusion/exclusion criteria. 
Patients who have consented to the study and have been randomized are considered enrolled. 
Patients who are issued a patient number, but who do not successfully complete the screening 
process and who do not get randomized will be considered screen failures. Patient numbers 
assigned to patients who screen fail will not be re-issued. 
2.2.2. 
Power and Sample Size  
2.2.2.1. 
Primary Endpoint 
The primary endpoint is PFS as per investigator assessment. The study is designed to test the null 
hypothesis that the survival function for PFS is the same between the MIRV arm and the IC 
chemotherapy arm versus the alternative hypothesis that the survival function for PFS is different 
between the MIRV and IC chemotherapy arms. 
Approximately 430 patients will be randomized 1:1 (approximately 215 patients each in the 
MIRV and IC chemotherapy arms, respectively) over a period of approximately 18 months. The 
final analysis will be conducted when at least 330 PFS events have been observed. 
The study will have 90% power to detect a hazard ratio of 0.7. An interim futility analysis will be 
conducted when at least 110 PFS events have been observed. The study may be terminated for 


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futility at interim analysis if the observed hazard ratio [MIRV to IC chemotherapy] is greater 
than 1. No alpha-spending is needed for this futility only analysis. 
Sample size and power were determined using R-Project package gsDesign version 2 with the 
following assumptions:  
• Median PFS for the IC arm is 3.5 months. 
• Median PFS for the MIRV arm is 5.0 months. 
• Exponential distribution for the event process. 
• Overall attrition rate is approximately 13% in both arms. 
• Uniform enrollment over an 18-month period. 
• Duration of follow up is 6 months. 
• Median OS for the IC Chemo arm is 12 months. 
• Median OS for the MIRV arm is 17.5 months. 
2.2.2.2. 
Power for Key Secondary Endpoints 
Only if the primary endpoint of PFS is statistically significant, a hierarchical testing procedure 
will be used to control the study-wise error rate (SWER) for key secondary endpoints of ORR, 
OS, and the primary PRO, in that order. 
ORR as Assessed by Investigator  
With a sample size of 430 (215 in each arm), the study will have a power of 91.8% to detect a 
14% difference in ORR (30% in MIRV vs 16% in IC chemotherapy). 
OS 
The final analysis of OS will be conducted when at least 300 events have occurred. There will be 
one interim analysis for OS at the time of final analysis of PFS at which time approximately 180 
(60%) deaths will have been observed. A Lan-DeMets alpha-spending function using an 
O’Brien-Fleming stopping boundary is used to control overall Type I error for OS at 2-sided 
alpha level of 0.05. The exact boundary at the interim OS analysis will be determined based on 
the actual number of death events. The study will have 90% power to detect an OS hazard ratio 
of 0.6857 and 80% power to detect an OS hazard ratio of 0.7235. The OS alpha-spending is 
calculated using R-Project package gsDesign version 2. 
Primary PRO Endpoint  
Primary PRO endpoint is proportion of patients achieving at least a 15-point (or equivalently, 
15%) improvement on the QLQ-OV28 abdominal/gastrointestinal symptom subscale [Items 31-
36] at the Week 8/9 assessment. This endpoint will be analyzed using a responder approach. 
Assuming a 90% compliance rate in the PRO endpoint, the study will have a power of 86% to 
detect a 15% difference in response rate for the primary PRO endpoint (25% in MIRV versus 
10% in IC chemotherapy).  


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2.2.3. 
Treatment Randomization and Stratification 
The treatment randomization schedule was developed by 4G Clinical. Patients will be 
randomized 1:1 into 2 groups, as follows: 
• Arm 1: MIRV six mg/kg AIBW Q3W.  
• Arm 2: IC chemotherapy (weekly Pac Q4W, PLD Q4W, or Topo administered either 
on Days 1, 8, and 15 Q4W or for 5 consecutive days Q3W.  
Randomization will be stratified as follows: 
• Number of prior lines of therapy (1 vs 2 vs 3). 
• IC chemotherapy (Pac, PLD, or Topo) choice prior to randomization. 
The required FRα expression level is ≥ 75% of tumor staining at ≥ 2+ intensity. 
2.2.4. 
Blinding and the BICR 
This is an open-label study. Treatment assignment will not be blinded because each study drug 
has a unique dosing schedule. A blinded independent central review (BICR) will be used to 
provide an independent assessment of radiographic tumor assessments. The BICR will be 
blinded to the treatment assignment. 
The Sponsor has also decided to blind certain members of the study team to the efficacy 
endpoints. Specifically, ImmunoGen statisticians and statistical programmers will not have 
access to the RECIST tumor assessments for either the Investigator’s assessment captured in the 
EDC system or the BICR data. 
Please see the Data Access Plan for this study for detailed information regarding the blinding of 
efficacy endpoints. 
2.2.4.1. 
BICR 
Copies of all imaging scans must be obtained and sent to a central imaging vendor designated by 
ImmunoGen as outlined in the Imaging Manual. The central imaging vendor will assess the 
quality of the images. The imaging vendor will be responsible for the formation and management 
of the BICR.  
Tumor response will be assessed by the Investigator and by the BICR using RECIST 
Version 1.1. Response as determined by the Investigator will be recorded in the electronic case 
report forms (eCRFs). The BICR assessment will be used as sensitivity analysis. 
2.2.5. 
Assessment Schedule 
See protocol Table 2, Table 3, and Table 4 for study schedules of assessments. 
2.3. 
Interventions 
2.3.1. 
Clinical Trial Material 
The dose levels and dosing schedule is provided in Table 2. 


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Table 2: 
Dosing and Dosing Schedule for Phase 3 Portion 
Phase 3 (Randomization 2:1) 
Group 
Drug 
Dose 
Dosing Schedule 
Arm 1 
IMGN853 
6 mg/kg AIBW 
Day 1 of a 3-week cycle  
Arm 2 
Paclitaxel 
80 mg/m2 
Days 1, 8, 15, and 22 of a 4-week cycle 
PLD 
40 mg/m2  
Day 1 of a 4-week cycle 
Topotecan (4-week cycle) 
4 mg/m2 
Days 1, 8, and 15 of a 4-week cycle 
Topotecan (3-week cycle) 
1.25 mg/m2  
Days 1 through 5 of a 3-week cycle  
AIBW = adjusted ideal body weight; PLD = pegylated liposomal doxorubicin. 
The protocol provides additional details in Section 4.1.2. 
3. 
GENERAL ANALYTICAL CONSIDERATIONS 
3.1. 
Data Sources 
Data are recorded on eCRFs. Central laboratory data will be provided via electronic data 
transfers. Section 12 of the protocol provides additional details regarding data recording and 
handling. Randomization is completed through an Interactive Response Technology (IRT) 
system.  
3.2. 
Definition of Baseline 
Study Day 1 (ie, Cycle 1 Day 1) will be designated as the first day a patient receives study drug. 
The baseline value is defined as the last non-missing value on or before the date of first dose of 
study drug.  
3.3. 
Missing Data 
Partial dates are allowed on the eCRF for prior anti-cancer systemic therapy start and stop dates, 
subsequent anti-cancer therapy start date, adverse event (AE) onset and resolution dates, 
concomitant medication start and stop dates, and concomitant 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 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 (ie, January 1), except for AEs occurring in the first year of dosing, 
in which case the date will be the first day of dosing.  


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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 (ie, 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 (ie, 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. 
• Procedure dates with missing month will be assumed to occur on the first day of the 
non-missing year (ie, January 1), except for procedures occurring in the first year of 
dosing, in which case the date will be the first day of dosing.  
For records with a missing prior anti-cancer systemic therapy start and/or stop date, and/or 
disease progression date from prior therapy, the following procedure will be employed for use in 
calculating the platinum-free interval (PFI):  
• If the stop date of prior platinum therapy is completely missing OR only the year is 
available, the PFI will be set as missing. 
• If both year and month of stop date of prior platinum therapy are available and only 
day is missing, the stop date will be imputed by the first day of the month. 
• If the disease progression date from prior platinum therapy is completely missing OR 
only the year is available, the PFI will be set as missing. 
• If both year and month of disease progression date from prior platinum therapy are 
available and only day is missing, the date of disease progression will be imputed by 
the last day of the month. 
For records with a missing subsequent anti-cancer therapy start date, the following procedure 
will be employed for use in deriving efficacy variables such as PFS and best overall response 
(BOR). 
• The start date of subsequent anti-cancer therapy will be imputed by the earliest 
possible date that is not contradicting with any other available data in the database. 


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For records with a partial death date, the following procedure will be employed for use in 
deriving time to event variables (PFS, OS, DOR, PFS2). 
• The death date will be imputed by the earliest possible date that is not contradicting 
with any other available data in the database. 
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.  
3.4. 
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 (eg, 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. 
3.5. 
Multiple Study Centers 
No adjustment for study center is planned.  
3.6. 
Covariate Adjustment in Primary Analysis 
A stratified analysis using randomization stratification factors will used for primary inference. 
The details are described in Section 5.2. 
3.7. 
Sample Size Reassessment 
Not applicable. 
3.8. 
Interim Analyses 
For the primary endpoint of PFS by investigator, the final analysis will be conducted when at 
least 330 events have been observed. An interim futility analysis was designed to be conducted 
when at least 110 events have been observed. The study would be terminated for futility at 
interim analysis if the observed hazard ratio [MIRV to IC chemotherapy] was greater than 1. No 
alpha spending was planned for this futility analysis. This interim futility analysis (IA1) was 
conducted with 131 PFS events (data cut 31 January 2022). Independent Data Monitoring 
Committee (IDMC) reviewed PFS results in a closed session, confirmed the futility boundary 
was not hit and recommended the trial to continue without modifications. 
Besides PFS, the interim futility analysis also included ORR and DOR analyses using the same 
method described in this document per FDA requests on 12 April 2022. No separate statistical 
analysis plan was prepared for the interim analysis. 
For the secondary endpoint of OS, the final analysis will be conducted when at least 300 deaths 
have been observed. There will be one interim analysis for OS at the time of final analysis of 
PFS at which time approximately 180 (60%) deaths will have been observed. A Lan-DeMets 
alpha-spending function using an O’Brien-Fleming stopping boundary is used to control overall 
Type I error for OS at 2-sided alpha level of 0.05. The exact boundary at the interim OS analysis 
will be determined based on the actual number of death events. 


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Additionally, there will be ongoing analysis of safety data by the Independent Data Monitoring 
Committee (IDMC) as described in the IDMC charter.  
3.9. 
Timing of Final Analysis 
If the study continues to a minimum of 430 patients for full enrollment (ie, the study is not 
stopped for futility at the interim analysis), the final analysis for PFS will be conducted when at 
least 330 PFS events have been observed (as determined by the investigator).  
3.10. 
Hypothesis Testing and Multiple Comparisons 
3.10.1. 
Primary Endpoint 
The null hypothesis for primary endpoint of PFS by investigator is: 
• H01: the survival function for PFSINV is the same between the MIRV arm and the IC 
chemotherapy arm. 
And the alternative hypothesis is: 
• Ha1: the survival function for PFSINV is different between the MIRV arm and the IC 
chemotherapy arm. 
For a single primary endpoint, there is no need to adjust for multiple comparison. 
3.10.2. 
Key Secondary Endpoints 
For the 3 key secondary endpoints, a hierarchical testing procedure will be applied to control the 
study-wise Type I error only if the null hypothesis for the primary endpoint is rejected at 2-sided 
α-level of 0.05. The order of the hierarchical testing is as follows: 
• ORRINV. 
• OS. 
• Primary endpoint for quality of life (QoLP): number of patients achieving at least a 
15% (or equivalently, 15-point) improvement on the QLQ-OV28 
abdominal/gastrointestinal symptom subscale [Items 31-36] at the Week 8/9 
assessment. 
The null hypothesis for ORRINV is as follows: 
• H02: the ORRINV is the same between the MIRV arm and the IC Chemo arm.  
And the alternative hypothesis is as follows: 
• Ha2: the ORRINV is different between MIRV arm and the IC Chemo arm. 
The null hypothesis for OS is as follows: 
• H03: the survival function for OS is the same between the MIRV arm and the IC 
Chemo arm.  
And the alternative hypothesis is as follows: 


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• Ha3: the survival function for OS is different between the MIRV arm and the IC 
Chemo arm.  
The null hypothesis for QoLP is as follows: 
• H04: the QoLP is the same between the MIRV arm and the IC Chemo arm.  
And the alternative hypothesis is as follows: 
• Ha4: the QoLP is different between the MIRV arm and the IC Chemo arm. 
Following this hierarchical testing procedure, if H03 is rejected favoring the MIRV arm at the 
final analysis for PFS, statistical significance will be claimed for OS and no further hypothesis 
testing is necessary for OS. In this case, however, an updated analysis of OS may still be 
conducted after 300 death events have occurred to provide updated estimate of treatment effect 
for OS. 
3.11. 
Analysis Populations  
Eight analysis populations will be defined for use with various analyses. Table 3 illustrates the 
relationship between each population and the analyses for which the data from the population 
will be used. 
Table 3: 
Analysis Populations 
Analysis Population 
Analysis 
Reason for 
Screen Failure 
Baseline 
Patient 
Disposition 
Efficacy 
Safety 
PK 
Screened 
X 
 
 
 
 
 
ITT 
 
X 
X 
X 
 
 
Per Protocol  
 
 
 
X 
 
 
Response Evaluable  
 
 
 
ORR only 
 
 
CA-125 Evaluable  
 
 
 
CA-125 only 
 
 
Safety 
 
 
 
 
X 
 
PK 
 
 
 
 
 
X 
LPP 
 
 
 
QoLP 
 
 
CA-125=cancer antigen 125; ITT=intent-to-treat; LPP= Longitudinal Period Population; ORR=objective response 
rate; PK=pharmacokinetics; QoLP=Primary endpoint for quality of life.  
3.11.1. 
Screened 
The Screened population includes all patients who have signed an informed consent.  
3.11.2. 
ITT Population 
The intent-to-treat (ITT) population is defined as all patients randomized to the study, regardless 
of whether or not patients received study treatment (MIRV or IC Chemo).  
Patients will be analyzed based on the randomized treatment.  


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3.11.3. 
Per Protocol Population 
Per Protocol Population is defined as all patients randomized to the study who have received at 
least 1 dose of MIRV or IC Chemo, excluding patients with protocol deviations in the following 
categories: patients - 
• whose tumors do not have FRα positivity as defined by the Ventana FOLR1 (FOLR-
2.1) CDx assay high expression, and/or  
• who have received four (4) or more prior lines of anticancer systemic therapy, and/or  
• who do not meet the eligibility criterion of being platinum resistant, and/or 
• who meet the protocol exclusion criterion of being primary platinum refractory. 
• Or other critical/major protocol deviations that deemed affecting primary and/or key 
secondary objectives. The final list of critical/major protocol deviations leading to the 
removal of patients from the per protocol population will be finalized and signed off 
before the database lock for the final PFS analysis. 
Patient will be analyzed based on the randomized treatment.  
3.11.4. 
Response-Evaluable Population 
The Response-Evaluable population is defined as all patients randomized to the study who have 
received at least 1 dose of MIRV or IC Chemo and have measurable disease at baseline per 
investigator or BICR. 
Patient will be analyzed based on the randomized treatment.  
3.11.5. 
CA-125-Evaluable Population 
The CA-125-Evaluable population is defined as all patients randomized to the study who have 
received at least 1 dose of MIRV or IC Chemo, whose pretreatment CA-125 is ≥ 2.0 times the 
upper limit of normal (ULN), within 2 weeks prior to randomization, and who have at least 1 
post-baseline CA-125 evaluation.  
Patient will be analyzed based on the randomized treatment.  
3.11.6. 
Safety Population 
All randomized patients who received at least 1 dose of MIRV or IC Chemo will be included in 
the Safety population. 
Patient will be analyzed based on the actual treatment received.  
3.11.7. 
Pharmacokinetic (PK) Analysis Population 
All randomized patients who received at least 1 dose of MIRV and who have at least one non-
missing PK concentration data point will be included in the PK analysis population. 


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3.11.8. 
Longitudinal Period Population (LPP) 
Longitudinal Period Population (LPP) defined as all randomized patients who have survived and 
maintained in the study from randomization through week 8/9 assessment and have available 
QoL data for both baseline and week 8/9.  
3.12. 
Data Display Characteristics 
Data displays produced for this study will include summary tables, data listings, and figures.  
Data listings will report the data recorded on the eCRF or derived for each patient. Data will be 
ordered by treatment, 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. 
Summary tables will display summary statistics calculated for each of the treatment groups. For 
safety analyses, the columns of the summary tables will be MIRV, IC Chemo total, Pac, PLD, 
Topo. For efficacy analyses, the columns of the summary tables will be MIRV and IC chemo.  
The summary statistics displayed will be a function of the type of data associated with the 
summarized assessment. Unless stated otherwise in relevant sections, 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. 
4. 
PATIENT ACCOUNTABILITY 
4.1. 
Patient Characteristics 
Patient characteristics will be summarized and listed for the ITT population by the treatment to 
which they were randomized (planned treatment). 
4.1.1. 
Demography 
Data collected about the following patient characteristics at the screening visit will be 
summarized as follows: 
• Age is collected in the IRT system at the time of patient registration. 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.  
− Childbearing potential (female only, yes/no). 
• Ethnicity. 
• Race. 


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• Region. 
• Country. 
All demographic data, including informed consent date, will be listed. 
4.1.2. 
Height and Baseline Weight, AIBW, and Body Surface Area 
Height and baseline weight, AIBW, and body surface area (BSA) will be summarized by 
treatment group and presented in a listing. 
4.1.3. 
Medical History 
Medical history will be coded using Medical Dictionary for Regulatory Affairs (MedDRA) 
(Version 24) and graded using NCI-CTCAE (version 5.0), associating lower-level terms with 
preferred terms (PTs) and system organ classes (SOCs) by the primary hierarchy. Medical 
histories will be summarized as the number and percentage of patients who reported at least 1 
medical history event; and number and percentage of patients who reported at least 1 medical 
history event in each SOC. Within each SOC, tables will display the number and percentage of 
patients reporting at least 1 medical history event as designated by PT. All medical history 
information will also be listed. 
4.1.4. 
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: 
• Eastern Cooperative Oncology Group Performance Status (ECOG) performance 
status  
• Primary diagnosis (epithelial ovarian cancer, fallopian tube cancer, primary peritoneal 
cancer, other) 
• FRα expression (percent staining at intensity 2+) 
• Histology 
• Disease stage at initial diagnosis 
• Histologic grade 
• Prior radiotherapy . 
• Prior systemic therapy  
− The number of prior systemic therapies is defined as the number of distinct 
treatment regimens. 
• Prior cancer related surgery. 
• Prior exposure to bevacizumab  
• Prior exposure to doxorubicin/PLD 
• Prior exposure to topotecan  


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• Prior exposure to taxanes  
• Prior exposure to PARP inhibitors  
− If patient participated in a double-blind randomized trial comparing PARP 
inhibitor to placebo and the actual treatment was unknown, patient will be 
summarized under ‘uncertain’ category. 
• Any breast cancer susceptibility gene (BRCA) mutations 
• Time since initial diagnosis (months) 
• Primary platinum-free interval (months) 
− Defined as time from last dose of 1st line platinum therapy to the date of disease 
progression and/or relapse following 1st line therapy. 
• Most recent Platinum-free interval 
− Defined as time from last dose of latest line platinum therapy to the date of 
disease progression and/or relapse following that line of therapy. 
4.2. 
Patient Disposition 
4.2.1. 
Screened and Enrolled Patients 
The number and percentage of patients who were screened, enrolled (randomized), not enrolled 
(screen failure), and reason for screen failure will be summarized overall, and by geographic 
region (North America, Europe, middle east and Africa, APAC), country, and site. 
4.2.2. 
ITT, Safety Disposition  
A summary of patient disposition will summarize, for the ITT population, the number of patients 
randomized and the reason for treatment and study discontinuation. This summary will also be 
produced for the Safety population if more than 5% of patients in the ITT population are 
excluded from the Safety population. 
Percentage of patients who withdrew for each reason on the End-of-Treatment and End-of-Study 
forms will be calculated using all members of the relevant population in the relevant treatment 
group for the denominator. 
The number and percentage of ITT patients included in each analysis population defined in 
Section 3.12 will be presented for each treatment group. This table will be produced for all 
patients at all sites, pooled. 
4.2.3. 
Protocol Deviations and Population Inclusions 
Protocol deviations will be captured in a protocol deviation log. A listing of patients with any 
protocol deviation will be provided for the ITT population.  
5. 
EFFICACY ANALYSES  
The PFS and OS efficacy analyses will use data from the ITT population. Patients will be 
analyzed by the treatment to which they were randomized (planned treatment).  


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5.1. 
Efficacy Outcomes 
5.1.1. 
PFS 
PFS is defined as the time from the date of randomization until the date of PD or death from any 
cause, whichever occurs first. PFS is defined based on radiological assessments and determined 
by the Investigator or the BICR (depending on the analysis). Clinical progression is not 
considered a progression endpoint.  
Table 4 summarizes 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 4: 
PFS Definitions  
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 randomization 
Date of randomization  
Censored 
No baseline tumor assessments or post-
baseline radiological assessments, and patient 
died within 105 days of randomization 
Date of death 
Death 
Death 
Date of death 
Death 
Radiological Progression 
Date of first radiological assessment 
indicating progression (i.e., OR = PD). 
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 PD 
Date of last radiological assessment 
Censored 
PD or death after missing 2 or more 
consecutive radiological assessments (PD or 
death date - last radiological assessment date 
+1 ≥ 105 days or >= 231 days if the assessment 
schedule has changed from every 6 weeks [+-1 
week] to every 12 weeks [+- 3 weeks] after 
Week 36 or after discontinuing from study 
treatment per local requirements) 
Date of last adequate radiological 
assessment showing no PD 
Censored 
Includes radiographic progression only.  
PFSINV is based on the Investigator’s assessment; PFSBICR is based on BICR assessment. 
OR = overall response; PD = disease progression; PFS = progression-free survival. 
5.1.2. 
Best Overall Response 
Best overall response (BOR) for a patient is the best response designation (as assessed by either 
the Investigator or the BICR, depending on the analysis) recorded between the date of 
randomization and the date of objectively documented PD per RECIST Version 1.1, the date of 
the start of new anti-cancer therapy, or the date of study discontinuation, whichever occurs first. 
When an analysis cutoff date is implemented, only radiological assessments occurring on or prior 
to the cutoff date will be used for analysis. Patients with an overall response of CR or PR must 


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have a repeat tumor assessment performed no less than 4 weeks (28 days) after the criteria for 
response are first met. When stable disease is the best overall response, it must meet the 
minimum duration of 35 days (6 weeks – 1 week window = 35 days from the date of first dose). 
The confirmatory scan is valid following treatment discontinuation as long as the patient has not 
started a new anti-cancer therapy.  
5.1.2.1. 
ORR 
The ORR will be calculated as proportion of patients with a BOR of CR or PR. Patients without 
post-baseline RECIST assessment will be treated as non-responders (ie, these patients will 
contribute to the denominator, but not the numerator). 
5.1.2.2. 
DOR 
DOR is defined as the time from the date of the first response (CR or PR), whichever occurs 
first, to the date of PD or death from any cause, whichever occurs first. DOR is only defined for 
patients who have a BOR 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. DOR end dates and censoring rules are the same as the PFS in 
Table 4 above. 
5.1.2.3. 
Time to Response 
Time to response (TTR) is defined as the time from the date of randomization until the date of 
the first observed CR or PR. TTR is only defined for patients who have a BOR of CR or PR. 
5.1.3. 
OS 
OS is defined as the time from the date of randomization 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 before the cutoff date are counted as OS events. Patients without death events 
will be censored on the latest date with a known alive status on or before the cutoff date. 
5.1.4. 
CA-125 Response 
A CA-125 response is defined as a ≥ 50% reduction in CA-125 levels from baseline. The 
response must be confirmed and maintained for at least 28 days. The CA-125 response will be 
conducted using the CA-125-Evaluable population. The date of response corresponds to the date 
when the CA-125 level is first reduced by 50%. The summary table for CA-125 will include the 
number (percentage) of patients in the CA-125-Evaluable population, and that sample size will 
then be used as the denominator for CA-125 response rate. 
5.1.5. 
RECIST-Related Endpoints –Investigator’s or BICR Assessment 
The primary analyses will use endpoints based on the investigator’s assessment of response. In 
the event that the primary endpoint of PFS by INV is positive, the BICR assessment of response 


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will be used for sensitivity analyses. A subscript of INV (Investigator) or BICR will indicate 
which assessment of response is used for the calculation of the endpoint. For example, BORINV 
and PFSINV will be used to denote the BOR and PFS based on the Investigator’s assessment of 
response; BORBICR and PFSBICR will be used to denote BOR and PFS based on the BICR 
assessment of response. 
5.1.6. 
PFS2 
PFS2 is defined as time from randomization to second PD or death. Specifically, for the purposes 
of the PFS2 analysis, the date of event was defined as the following, whichever occurred first:  
• Date the patient experienced an event of radiological or clinical progression reported 
on the response follow-up forms.  
• Date of death.  
• Date of end of next-line treatment.  
− For next-line treatment, any therapy other than radiotherapy or surgery will be 
considered.  
• Any event of PD reported during the survival follow-up evaluation will be 
considered, including PD in patients who did not receive subsequent next-line 
treatment.  
• Patients who did not experience PD by INV during the study period but who had PD 
documented on the response follow-up form will also be considered as having an 
event of PFS2.  
• For patients who did not receive subsequent therapy, nor experience PD or death 
during any follow-up, the data will be censored at the time of the last follow-up 
contact.  
• Data from patients lost to follow-up after at least 1 follow-up assessment will be 
included in the analysis as censored observations on the date the patient was last 
known to be alive.  
• Patients who did not have follow-up contacts will be censored on the date of study 
discontinuation. 
5.2. 
Primary Efficacy Outcome Analysis 
The protocol specifies the following primary efficacy endpoint: 
• PFS as assessed by the investigator (PFSINV). 
The distribution of PFSINV will be summarized using the Kaplan-Meier method. PFS rates will 
be reported at 3-month intervals (eg, 3 months, 6 months, etc.). Median times will be estimated 
for each treatment from the 50th percentile of the corresponding Kaplan-Meier estimates. 95% 
confidence intervals (CI) for the 3-month intervals and median times will also be provided. The 
primary comparison between treatments will use the log-rank test stratified by the randomization 
stratification factors. Stratified analysis using values collected on the eCRFs will be conducted as 


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sensitivity analysis. As a sensitivity analysis, the results from an unstratified analysis will also be 
provided. The chi-square p-values from the log-rank tests will be reported. 
Additionally, the restricted mean survival time (RMST) for PFSINV will also be reported at 3-
month intervals (eg, 3 months, 6 months, etc.). The RMST at 12 months will be compared 
between treatments stratified by the randomization stratification factors using SAS PROC 
RMSTREG. As a sensitivity analysis, the RMST from an unstratified analysis will also be 
provided.  
In stratified analysis, the strata will be IC Chemo (Pac vs PLD vs Topo) and the number of prior 
lines of therapy (1 vs 2 vs 3).  
The hazard ratio for PFSINV treatment comparisons will be estimated using a stratified Cox 
proportional hazards model. As a sensitivity analysis, the hazard ratio from an unstratified Cox 
proportional hazards model will also be provided. The Supremum test will be conducted to test 
for proportional hazards assumption. 
The hazard ratio (MIRV arm vs IC Chemo arm) will be reported using the maximum likelihood 
estimate along with 95% CI. The IC Chemo arm will be used as the reference treatment (ie, 
denominator of the hazard ratio). A time-to-event hazard ratio less than 1.0 would indicate a 
MIRV benefit over IC Chemo. 
As a sensitivity analysis, PFSINV will also be analyzed in the Per-protocol population. Patients 
will be analyzed by the actual treatment they received in this sensitivity analysis. 
5.3. 
Secondary Efficacy Analyses 
5.3.1. 
Key Secondary Efficacy Analyses 
The protocol describes the following key secondary efficacy endpoints: 
• ORR per RECIST Version 1.1 criteria based on the investigator’s assessment 
(ORRINV). 
• OS. 
• Primary PRO endpoint (QoLP): Number of patients achieving at least a 15% (or 
equivalently, 15-point) improvement on the QLQ-OV28 abdominal/gastrointestinal 
symptom subscale [Items 31-36] at the Week 8/9 assessment). 
Only if the primary endpoint of PFS by INV is positive, a hierarchical testing procedure will be 
applied to key secondary endpoints (in the order listed above) to control the study-wise Type I 
error. 
Unless noted otherwise, all analyses of key secondary endpoints will be based on the ITT 
population. In addition, ORR will also be summarized using the Response-Evaluable population 
and QoLP will be summarized using the LPP population. 
As a sensitivity analysis, ORR and OS will also be summarized on the Per-protocol population. 
ORR will be analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by the 
randomization stratification factors to test for differences between the MIRV arm and the IC 


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Chemo arm. P-value and 95% CIs for ORR will be provided. Odds ratio and its 95% CI will also 
be reported. 
The distribution of OS will be summarized using the Kaplan-Meier method. OS rates will be 
reported at 3-month intervals (eg, 3 months, 6 months, etc.). Median OS will be estimated for 
each treatment from the 50th percentile of the corresponding Kaplan-Meier estimates. 95% CIs 
for the 3-month intervals and median OS will also be provided. The primary comparison 
between treatments will use the log-rank test stratified by the randomization stratification factors. 
Stratified analysis using values collected on the eCRFs will be conducted as sensitivity analysis. 
As a sensitivity analysis, the results from an unstratified analysis will also be provided. The chi-
square p-values from the log-rank tests will be reported.  
The hazard ratio for the OS treatment comparisons will be estimated using a stratified Cox 
proportional hazards model. As a sensitivity analysis, the hazard ratio from an unstratified Cox 
proportional hazards model will also be provided. The Supremum test will be conducted to test 
for proportional hazards assumption. 
The hazard ratio (MIRV arm vs IC Chemo arm) will be reported using the maximum likelihood 
estimate along with 95% CI. The IC Chemo arm will be used as the reference treatment (ie, 
denominator of the hazard ratio). A hazard ratio less than 1.0 would indicate a MIRV benefit 
over IC Chemo. 
The median follow up time and its 95% CI will be estimated using reverse Kaplan-Meier method 
on OS. 
The number of IC Chemo patients who received MIRV post study treatment will be closely 
monitored. Additional sensitivity analyses to adjust for bias due to crossover (e.g., two-stage 
estimation, inverse probability censoring weighting) will be evaluated and conducted, if deemed 
necessary. 
For QoLP analysis, patients will be classified into the following categories based on their QLQ-
OV28 abdominal/GI symptom subscale scores: 
• If a patient’s score on the QLQ-OV28 abdominal/GI symptom subscale increases by 
15 points or greater from baseline to week 8/9 assessment, the patient will be 
categorized “Improved”. 
• If a patient’s score on the QLQ-OV28 abdominal/GI symptom subscale increases by 
less than 15 points from baseline to week 8/9 assessment, the patient will be 
categorized “Unimproved”. 
• If a patient died or progressed prior to week 8/9 assessment, the patient will be 
categorized “Unimproved”. 
A Cochran-Mantel-Haenszel (CMH) test stratified by the randomization stratification factors to 
test for differences between the MIRV arm and the IC Chemo arm will be performed. All two-
sided P-values from these tests will be reported.  
5.3.2. 
Other Secondary Efficacy Analyses 
Additionally, the following efficacy endpoints will also be analyzed: 


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• DOR based on Investigator’s assessment (DORINV). 
• TTR based on Investigator’s assessment (TTRINV). 
• GCIG CA-125 criteria clinical response rate. 
Because there is no procedure in place to control the Type I error on other secondary efficacy 
endpoints, all p-values for treatment comparison on other secondary efficacy endpoints will be 
for information only and will be considered as nominal.  
GCIG CA-125 response will be summarized using the CA-125 Response-Evaluable population 
only. 
DOR and TTR will be summarized in patients with a BOR of CR or PR only. 
GCIG CA-125 response will be analyzed using a CMH test stratified by the randomization 
stratification factors to test for differences between the MIRV arm and the IC Chemo arm. P-
value and 95% CIs for the proportion of patients with GCIG CA-125 clinical response will be 
provided. Odds ratio and its 95% CI will also be reported. 
The distribution of DOR will be summarized using the Kaplan-Meier method. Kaplan-Meier 
estimate of DOR will also be reported at 3-month intervals (eg, 3 months, 6 months, etc.). 
Median DOR will be estimated for each treatment from the 50th percentile of the corresponding 
Kaplan-Meier estimates. 95% CIs for the 3-month intervals and median DOR will also be 
provided. Because DOR will be analyzed for the subset of patients who achieved a BOR of CR 
or PR, the primary comparison between treatments will use the unstratified log-rank test. The 
chi-square p-values from the log-rank tests will be reported.  
The hazard ratio for DOR treatment comparisons will be estimated using an unstratified Cox 
proportional hazards model. The hazard ratio (MIRV arm vs IC Chemo arm) will be reported 
using the maximum likelihood estimate along with 95% CI. The IC Chemo arm will be used as 
the reference treatment (ie, denominator of the hazard ratio). A hazard ratio less than 1.0 would 
indicate a MIRV benefit over IC Chemo. 
TTR will be summarized using descriptive statistics for patients who achieved a confirmed 
response of CR or PR.  
If the primary endpoint of PFS by INV is statistically significant, PFS, ORR, DOR, and TTR by 
BICR will be analyzed using the same methods as in investigator assessed PFS, ORR, DOR and 
TTR as sensitivity analysis.  
Analysis of other PRO endpoints will be described in a separate document to the SAP. 
PFS2 analysis will be conducted using the same method as in PFS analysis. 
5.4. 
Exploratory Efficacy Analyses 
The protocol describes the following exploratory efficacy analyses: 
• Evaluate association of BRCA mutation status and FRα expression level with anti-
tumor activity of MIRV.  


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• Evaluate the association of anti-tumor activity and/or safety with the following:  
− Soluble FRα level in blood samples. 
5.5. 
Efficacy Analysis on Subgroups of Patients 
PFSINV, ORRINV, and OS will be analyzed with the following subgroups of patients: 
• BRCA status (positive vs negative/unknown). 
• Age (< 65 year vs ≥ 65 years). 
• Baseline Eastern Cooperative Oncology Group Performance State (ECOG PS) (0 vs 
1). 
• Prior exposure to bevacizumab.  
• Number of prior lines of therapy.  
• Primary platinum-free interval (≤6 months vs >6 months). 
• Most recent Platinum-free interval (≤3 months vs >3 months). 
• Prior exposure to PARPi maintenance therapy (yes vs no vs uncertain). 
• Country (USA vs rest of world). 
• Stage at diagnosis (I-III vs IV). 
• Weight at baseline (<=60kg, 60-80kg, >80kg). 
The summaries for time to event variables include the number and percentage of events, median 
and its 95% CI, 2-sided P-value, and hazard ratio (MIRV to IC chemo) and its 95% CI. 
The forest plot of time to event variables will display the number of subjects, events, hazard ratio 
(MIRV to IC chemo) and its 95% CI. 
The summaries for ORR include the ORR and its 95% CI, and odds ratio and its 95% CI. 
The forest plot of ORR will display the number of subjects, odds ratio and its 95% CI.  
All subgroup analyses will be unstratified. 
Due to potential small number of patients will be eligible for DOR analysis, no subgroup 
analyses will be conducted for DOR. 
5.6. 
Additional Sensitivity Analyses 
The primary analyses for PFS are based on the investigator assessment of radiological assessments 
only. If PFSINV is statistically significant, a sensitivity analysis of PFS based on the BICR 
assessment (PFSBICR) is described Section 5.3. As an additional sensitivity analysis, PFS will be 
re-assessed by using the Investigator’s radiological and clinical assessments (PFSAINV). In this 
analysis, PFSAINV will be defined as the time from the date of the randomization until the date of 
PD by radiological or clinical assessment or death from any cause, whichever occurs first, as 
determined by the Investigator. If PD is noted in both clinical and radiological assessments, the 
first date where PD is noted will be used for analysis. 


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Table 5: 
PFSAINV Definitions  
Includes Investigator assessed radiological and clinical progression. 
eCRF = electronic case report form; OR = overall response; PD = disease progression; PFS = progression-free 
survival; RECIST = Response Evaluation Criteria in Solid Tumors. 
Additionally, for PFSINV, rather than censoring patients who progressed or died after missing 2 
or more consecutive radiological assessments, the date of the PFS event will be backdated to the 
date of first missed assessment. This analysis will be called PFSBINV. Table 6 provides the rules 
for PFSBINV. 
 
Situation 
Date of PFS Event or Censoring 
Outcome 
No baseline tumor assessments or 
post-baseline tumor assessments, and 
patient did not die within 105 days of 
randomization and no clinical progression 
noted 
Date of randomization  
Censored 
No baseline tumor assessments or 
post-baseline tumor assessments, and 
patient died within 105 days of 
randomization and no clinical progression 
noted 
Date of death 
Death 
Death 
Date of death 
Death 
Radiological or clinical progression 
The earliest of: 
Date of first radiological assessment 
indicating progression (ie, OR = PD on 
RECIST response eCRF), or 
Date of first instance of clinical 
progression. 
Progression 
New anti-cancer therapy prior to 
progression 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 
Progression (radiological or clinical) or 
death after missing 2 or more consecutive 
radiological assessments  
(PD or death date - last radiological 
assessment date + 1 ≥ 105 days or >= 231 
days if the assessment schedule has changed 
from every 6 weeks [+-1 week] to every 12 
weeks [+- 3 weeks] after Week 36 or after 
discontinuing from study treatment per 
local requirements) 
Date of last RECIST assessment 
Censored 


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Table 6: 
PFSB INV Definitions  
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 
randomization 
Date of randomization 
Censored 
No baseline tumor assessments or 
post-baseline radiological assessments, and 
patient died within 105 days of randomization 
Date of death 
Death 
Death 
Date of death 
Death 
Progression 
Date of first radiological assessment 
indicating progression (ie, OR = PD). 
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 2 or more 
consecutive radiological assessments (PD or 
death date - last radiological assessment date 
+1 ≥ 105 days or >= 231 days if the 
assessment schedule has changed from every 
6 weeks [+-1 week] to every 12 weeks [+- 3 
weeks] after Week 36 or after discontinuing 
from study treatment per local requirements). 
Date of first missed radiological 
assessment (ie, date of the last adequate 
assessment + 42/84 days [ie, 
6/12 weeks]). 
Progression 
Includes radiographic progression only. 
OR = overall response; PD = progressive disease or disease progression; PFS = progression-free survival. 
Additionally, PFSRINV will be analyzed by not censoring patients receiving palliative 
radiotherapy during study treatment while everything else is identical to PFSINV. Table 7 
provides the rules for PFSRINV. 
Table 7: 
PFSRINV Definitions  
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 randomization 
Date of randomization  
Censored 
No baseline tumor assessments or post-
baseline radiological assessments, and patient 
died within 105 days of randomization 
Date of death 
Death 
Death 
Date of death 
Death 
Radiological progression 
Date of first radiological assessment 
indicating progression (ie, OR = PD) 
Progression 
New anti-cancer therapy prior to PD or death 
(not including palliative radiotherapy during 
study treatment) 
Date of last radiological assessment 
prior to the start of the new anticancer 
therapy 
Censored 


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Table 7: 
PFSRINV Definitions  (Continued) 
Situation 
Date of PFS Event or Censoring 
Outcome 
No death or progression 
Date of last radiological assessment 
Censored 
PD or death after missing 2 or more 
consecutive radiological assessments (PD or 
death date - last radiological assessment date 
+ 1 ≥ 105 days or >= 231 days if the 
assessment schedule has changed from every 
6 weeks [+-1 week] to every 12 weeks [+- 3 
weeks] after Week 36 or after discontinuing 
from study treatment per local requirements) 
Date of last adequate radiological 
assessment showing no PD 
Censored 
Includes radiographic progression only. 
OR = overall response; PD = progressive disease or disease progression; PFS = progression-free survival. 
If the primary endpoint of PFSINV is statistically significant, the following sensitivity analyses 
will also be performed: 
• The concordance/discordance rate between the PFS outcomes for the BICR 
assessment and the INV assessment will be summarized. 
• The concordance/discordance rate between the BICR Best Overall Response and the 
INV Best Overall Response will be summarized. 
5.7. 
Strategies for Pooling Stratification Factors 
This study uses 2 factors to stratify patients for randomization, with a total of 9 stratification 
levels. At the final analysis, there may be a small number of patients in 1 or more of the 
stratification levels. The following strategy for pooling stratification levels will be used if 1 or 
more of the stratification levels contains fewer than 12 patients (Table 8).  
After pooling, each stratum is expected to have at least 1 event at the final analysis.  
Table 8: 
Pooling of Stratification Factors 
Priors 
IC Chemo 
If n < 12 Pool With 
1 
PLD 
Next stratum 
1 
Pac 
Previous stratum 
1 
Topo 
Previous stratum 
2 
PLD 
Next stratum 
2 
Pac 
Previous stratum 
2 
Topo 
Previous stratum 
3 
PLD 
Next stratum 
3 
Pac 
Previous stratum 
3 
Topo 
Previous stratum 
IC = Investigator’s choice; Pac = paclitaxel; PLD = pegylated liposomal doxorubicin; Topo = topotecan. 


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5.8. 
Other Efficacy-related Summaries 
New anti-cancer therapy data will be summarized for the ITT population by randomized arm as 
follows: 
• Number and percentage of patients receiving new anti-cancer therapy. 
• Type of new anti-cancer therapy. 
− Taxanes. 
− Topotecan. 
− Platinum compounds. 
− Anthracyclines. 
− Chemotherapy (other). 
− Bevacizumab. 
− Doxorubincin\PLD 
− Hormonal therapy. 
− Kinase inhibitors. 
− Mirvetuximab soravtansine. 
− PARP inhibitors. 
− PD-1/PD-L1 inhibitors. 
− Immunotherapy 
− Investigational/blinded therapy 
− Other. 
Listings of efficacy-related data for will include the following: 
• All lesion assessments (target lesion, non-target lesion, new lesion). 
• New anti-cancer therapy. 
• Investigator’s RECIST assessments. 
• (BICR RECIST assessments). 
• CA-125 results. 
• Derived parameters for CA-125 response, BOR, PFS, DOR, OS, and PFS2. 
• Censoring for time-to-event variables. 
 


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6. 
SAFETY ANALYSES 
The main safety summary tables will use data from the Safety population. Patients will be 
analyzed according to the actual study drug received.  
Listings will be provided for patients in the Safety population. The actual study drug received 
will be displayed on the listing. 
6.1. 
Exposure 
Summary tables will be provided with the following information. 
Exposure to MIRV, paclitaxel, topotecan, and PLD will be summarized in tables with descriptive 
statistics for the number of doses received, the number of cycles received, duration of dosing 
(weeks and months), total cumulative dose ( mg), absolute dose intensity (mg/kg/dose for 
IMGN853, calculated as total cumulative dose [mg])/number of valid drug administration 
records /AIBW (kg); mg/m2/dose for remaining investigational products, calculated as total 
cumulative dose (mg)/number of valid drug administration records/BSA (m2)), and relative dose 
intensity (percentage of planned, calculated as [absolute dose intensity/6] × 100 for IMGN853, 
[absolute dose intensity/80] × 100 for paclitaxel, [absolute dose intensity/40] × 100 for PLD, 
[absolute dose intensity/1.25] × 100 for topotecan 1.25 mg/m2, [absolute dose intensity/4] × 100 
for topotecan 4 mg/m2). 
Duration of dosing in weeks are calculated as the following: 
MIRV: (last dose date – first dose date + 21)/7 
Pac: (last dose date – first dose date + 7)/7 
PLD: (last dose date – first dose date + 28)/7 
Top (Q4W): (last dose date – first dose date + 14)/7 
Top (Q3W): (last dose date – first dose date + 16)/7 
If a patient is allowed to change Top from Q4W to Q3W in the middle of study, then dose 
density calculation needs to break into two parts.  
The number of patients who received MIRV will also be summarized by drug lot numbers. 
A listing will be provided with the information from all study drug administration eCRFs over 
the treatment period.  
6.2. 
AEs 
AEs 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 drug or until the event has 
resolved, stabilized, or returned to baseline. AEs attributed to study procedures, including those 
events that occur prior to the first dose, should also be documented on the AE eCRF.  
AE data are available to ImmunoGen from 2 sources, the eCRFs and the serious adverse event 
(SAE) forms. While reconciliation will be performed, the production of data summaries and 
listings will be based on the data collected on the eCRF.  


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Pre-treatment AEs are defined as AEs with an onset date prior to the first dose of study drug. 
TEAEs are defined as AEs with an onset date on or after the first dose of study drug, and within 
30 days of the last dose of study drug or prior to the start of a new anti-cancer treatment, 
whichever occurs first. Medical history conditions that exist before the initiation of study drug 
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 24.0 or later), associating lower-level 
terms with PT and SOC by the primary hierarchy. The tables will display the counts and 
percentages of patients who reported at least 1 TEAE in each SOC represented in the AE data. 
Within each SOC, the tables will display the counts and percentages of patients reporting at least 
1 TEAE as designated by the PT. 
AEs are graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 
AE summaries may include summaries for all AEs and by the maximum CTCAE grade for the 
item being summarized (ie, 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. 
AEs that are definitely, probably or possibly related to the study drug will be considered as 
related to the study drug. AEs with missing or unknown relationship to the study drug are 
considered as related to the study drug. AEs with the closest relatedness to the study drug will be 
used for summaries. 
The following AE summary tables will be produced:  
• An overall summary of safety and the number of patients who died during the study 
or within 30 days of last dose. 
• All TEAEs by SOC and PT. 
• Serious TEAEs by SOC and PT. 
• Non-Serious TEAEs (ie, TEAEs excluding SAEs) by SOC and PT. 
• Grade 3 or higher TEAEs by SOC and PT. 
• TEAEs leading to drug withdrawal. This subset includes TEAEs with an action taken 
of drug permanently discontinued. 
• Related TEAEs leading to drug withdrawal. This subset includes TEAEs related to 
study drug with an action taken of drug permanently discontinued. 
• TEAEs related to study drug by SOC and PT. An AE reported by a patient more than 
once will be included in this table if at least 1 of the drug association grades is 1 of 
the grades listed here. 
• Serious, related TEAEs by SOC and PT. An AE reported by a patient more than once 
will be included in this table if at least 1 of the drug association grades is 1 of the 
grades listed here. 


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• TEAEs leading to dose modifications (dose reduction, dose not given or dose delay). 
− TEAEs leading to dose reduction. 
− TEAEs leading to dose delay. 
− TEAEs leading to dose reduction, dose not given or dose delay. 
• Related TEAEs leading to dose modification (dose reduction, dose not given or dose 
delay). 
− Related TEAEs leading to dose reduction. 
− Related TEAEs leading to dose delay. 
− Related TEAEs leading to dose reduction, dose not given, or dose delay. 
• Deaths on study treatment or within 30 days of the last dose. This table includes all 
deaths during study treatment or within 30 days of the last dose, regardless of cause 
of death. 
• TEAEs leading to death. This table includes all TEAEs with CTCAE Grade 5. 
• Related TEAEs leading to death. This table includes all TEAEs related to study drug 
with CTCAE Grade 5. 
The following listings will be produced:  
• All AEs, sorted chronologically by patient. This listing includes SOC, PT, 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 resulting in death. This listing includes TEAEs with a CTCAE grade of Grade 
5 (death). 
• survival status. 
The following groupings of TEAEs will be generated as part of the focused analysis of safety: 
• Ocular TEAEs. 
• Peripheral neuropathy TEAEs. 
• Pneumonitis. 
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 by PT and maximum CTCAE grade. 
• Time to first onset of each group of TEAEs. 
• Action taken with study drug with respect to each group of TEAEs. 


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Actions include:  
− Dose permanently discontinued. 
− Dose reduced. 
− Dose delayed/not given. 
− Infusion interruption. 
A subject could have multiple actions above. 
• Worst outcome for TEAEs of interest 
− Dose permanently discontinued. 
− Dose reduced. 
− Dose delayed/not given. 
− Infusion interruption. 
− No action taken. 
Severity of action is based on order above. A subject is only counted once in the 
worst category.  
• Resolution status. 
For the focused safety analysis, the following listings will be produced: 
• Ocular TEAEs. 
• Peripheral neuropathy TEAEs. 
• Pneumonitis TEAE. 
6.2.1. 
Fresh Biopsy Patient Adverse Events 
Summary of adverse events, not necessarily TEAEs, experienced within 7 days of biopsy will be 
generated by SOC, PT and CTCAE grade. A listing of AEs experienced within 7 days of biopsy 
will also be generated for patients who have undergone fresh biopsy. 
6.2.2. 
Infusion-related Reactions 
Infusion related reactions will be analyzed using Standard MedDRA Query (SMQ) with the 
keyword of hypersensitivity (narrow) and PT terms 'flushing', 'erythema', 'erythema of eyelid'. A 
summary table of all TEAEs will be generated by SOC, PT, and CTCAE grade. A listing will 
also be generated. 
6.3. 
Clinical Laboratory Results 
Laboratory test results (including hematology, coagulation, serum chemistry, and urinalysis) and 
abnormal laboratory values will be presented in data listings. 
CTCAE Version 5.0 laboratory grades will also be presented. CTCAE grades will be derived 
based on laboratory results and will not factor in clinical evaluations. 


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Shift tables summarizing the changes from baseline in severity of laboratory grades will be 
provided for laboratory parameters graded according to CTCAE Version 5.0  
Clinically significant values in liver function tests (LFTs) will be summarized by the following 
categories, using the maximum value while on study drug. The denominator for the summaries 
will be the number of patients who had at least 1 non-missing value during treatment. The 
categories for each test are not mutually exclusive: 
• Aspartate aminotransferase (AST). 
− > 3 × ULN. 
− > 5 × ULN. 
− > 10 × ULN. 
− > 20 × ULN. 
• Alanine Aminotransferase (ALT). 
− > 3 × ULN. 
− > 5 × ULN. 
− > 10 × ULN. 
− > 20 × ULN. 
• AST or ALT. 
− > 3 × ULN. 
− > 5 × ULN. 
− > 10 × ULN. 
− > 20 × ULN. 
• Total bilirubin (TBL). 
− > 1.5 × ULN. 
− > 2 × ULN. 
• Alkaline phosphatase (ALP). 
− > 1.5 × ULN. 
• (AST or ALT) and TBL (concurrent). 
− AST or ALT > 3 × ULN and TBL > 1.5 × ULN. 
− AST or ALT > 3 × ULN and TBL > 2 × ULN. 
• (AST or ALT) and ALP and TBL (concurrent). 
− AST or ALT > 3 × ULN and ALP < 2 × ULN and TBL > 2 × ULN. 
Here, concurrent means that all the associated LFTs must be from the same visit. In addition, 
worst postbaseline grade for LFTs will be summarized. Because baseline values of LFTs are 


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already taken into account in CTCAE V5.0, shift table from baseline to worst postbaseline grade 
will not be generated for LFTs. 
Results from pregnancy tests will be provided in listings.  
6.4. 
Vital Signs 
Vital signs (including temperature, pulse rate, systolic blood pressure, diastolic blood pressure, 
and respiratory rate) will be collected throughout the study.  
Vital signs results will be classified into 4 or 5 categories (low, borderline low, normal, 
borderline high, or high) according to Table 9 below. Shift tables based on this classification will 
be summarized from baseline to the last post-baseline visit value. 
Table 9:  
Classification of Vital Signs 
Vital Sign 
Low 
Borderline 
Low 
Normal 
Borderline 
High 
High 
Heart Rate (beats per 
minute) 
< 50 
50-59 
60-90 
91-99 
≥ 100 
Systolic BP (mmHg) 
< 80 
- 
80-120 
121-139 
≥ 140 
Diastolic BP (mmHg) 
< 60 
- 
60-80 
81-89 
≥ 90 
Respiratory Rate 
(breaths per minute) 
< 12 
- 
12-20 
21-24 
≥ 25 
Temperature (°C) 
< 35.0 
35.0-36.4 
36.5-37.2 
37.3-37.9 
≥ 38.0 
6.5. 
ECGs 
All ECG results will be presented in data listings. If a different correction for QT is captured in 
the eCRF, that QTc will be reported in the listing for that patient with QTcF.  
6.6. 
Concomitant Medications 
All medications and supportive therapy taken within 4 weeks prior to 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, 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 drug.  
Concomitant medications are defined as medications which are taken during the course of study 
treatment and within 30 days of the last dose of study drug, as follows:  
• Medications started before the first dose of study drug, but with a stop date after the 
first dose of study drug and within 30 days of the last dose of study drug will be 
considered concomitant medications.  
• Medications started before the first dose of study drug that are ongoing will be 
considered concomitant medications. 


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• Medications started after the first dose of study drug and within 30 days of the last 
dose of study drug or before the start of a new anti-cancer treatment, whichever 
occurs first, are considered concomitant medications.  
• Medications started before the first dose of study drug, but with a stop date after the 
first dose of study drug and within 30 days of the last dose of study drug or prior to 
the start of a new anti-cancer treatment, whichever occurs first, will be considered 
concomitant medications.  
Prior and concomitant medications will be coded using the September 2019 or later version of 
World Health Organization drug dictionary (WHO Drug). 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 number and percentage of patients who 
reported using at least 1 medication in each represented pharmacological subgroup. If a patient 
has more than 1 medication in the subgroup, the patient will be counted only once. 
A complete listing of medications will be generated by patient. The listing will indicate which 
medications are prior and which are concomitant. The listing will display entries from the 
concomitant medications form, ordered within patient by start date. The listing will display the 
recorded term from the eCRF and the WHO Drug anatomical main class (ATC Level 1 term) and 
pharmacological subgroup (ATC Level 3 term). 
6.7. 
Concomitant Procedures 
All procedures within 4 weeks of Cycle 1 Day 1 and through 30 days after last study treatment 
must be recorded on the appropriate eCRF.  
Prior procedures are defined as occurring before the first dose of study drug (by procedure date).  
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 or prior to the start of a new anti-
cancer treatment, whichever occurs first.  
Prior and concomitant procedures will be coded using MedDRA (Version 24), associating lower-
level terms with PT and SOC by the primary hierarchy. Summary tables will be provided for 
prior and concomitant procedures. The tables will display number and percentage of patients 
who reported at least 1 procedure in each SOC represented in the eCRF data. Within each SOC, 
the tables will display number and percentage of patients reporting at least 1 concomitant 
procedure as designated by PT. 
A complete listing of procedures will be generated. The listing will indicate which procedures 
are prior and which are concomitant. The listing will display entries from the concomitant 
procedures form, ordered within patient by date of procedure. The listing will display the 
recorded term from the eCRF and the SOC and PT.  


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6.8. 
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. 
Worst decline in both eye best corrected visual acuity (BCVA) grade will be summarized. Shift 
of both eye BCVA from baseline to worst post baseline will be summarized using the following 
categories: more than two lines of improvement, two lines improvement, one line of 
improvement, less than one line change in visual acuity, one line worsening, two lines 
worsening, more than two lines of worsening. 
Intraocular pressure elevations will be summarized by the number of subjects with 7 mmHg 
elevations or greater post baseline.  
6.9. 
Ocular Symptom Assessments 
Results of the ocular assessments will be presented in data listings.  
6.10. 
Corticosteroid and Lubricating Eye Drop Compliance 
All compliance information collected on the eCRF will be presented in data listings. 
6.11. 
Transfusions 
All transfusions recorded on the eCRF will be presented in data listings.  
6.12. 
ECOG PS 
ECOG PS results will be presented in data listings. Baseline ECOG PS will be summarized in 
disease characteristics table. 
6.13. 
ECHO/MUGA 
Echocardiogram (ECHO)/multiple gated acquisition (MUGA) scans are taken only for patients 
receiving PLD. All ECHO/MUGA results will be presented in data listings.  
7. 
PRO 
Analyses for PRO, including quality of life and healthcare resource utilization, will be covered 
by a separate, independent analysis plan by the PRO vendor, in collaboration with ImmunoGen. 
8. 
IMMUNOGENICITY 
Anti–MIRV seroconversion refers to the development of detectable antibodies that bind to 
MIRV and is based upon positive results in both screening and confirmatory assays. Patients will 
be classified as follows: 
• Patients who had a baseline-negative ADA result who developed ADAs at any time 
after initial administration of drug. 


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• Treatment-enhanced ADAs: Patients who had a baseline positive ADA result in 
whom the assay signal was enhanced (greater than baseline titer by ≥ 4 folds) at any 
time after initial drug administration. 
• Treatment-unaffected ADA: Patients who had a baseline-positive ADA result in 
whom the assay signal was not enhanced (not greater than baseline titer by ≥ 4 folds) 
at any time after initial drug administration. 
• Seronegative: a patient who tests negative at all visits. 
If a titer is below LLQ, it will be imputed as half of LLQ. 
Efficacy endpoints PFS and ORR will be analyzed by the above ADA status group. 
TEAE by SOC and PT will be summarized for the above ADA status group. 
9. 
BIOMARKERS 
The exploratory biomarker analyses for this study will be covered by a separate, independent 
analysis plan.  
10. 
PHARMACOKINETICS 
Plasma concentration data collected in this study will be listed and summarized in the PK 
analysis population. Mean and 95% CI, standard deviation, geometric mean, coefficient of 
variation (CV, expressed as percentage), median, Q1, Q3, min, and max will be reported by visit. 
Data points that are below the lower limit of quantitation will be excluded from the analyses. 
11. 
REVISION HISTORY 
Table 10: 
Revision History 
Version 
Effective Date 
Comments 
1 
10Oct 2019 
Initial document 
2.0 
23Mar 2020 
1. Added PK analysis population 
2. Removed reference to iSAP  
3. Specified comparison of RMST at 12 months between treatment 
arms 
4. Removed location of metastasis 
5. Changed CTCAE version to 5.0 
6. Clarified how to summarize LFT CTCAE grades due to changes 
from v4.03 to 5.0 
3.0 
14Feb 2023 
1. Clarification on longitudinal period population 
2. Clarification on censoring rule for missing 2 or more 
consecutive radiological assessments. 
3. Updated on BCVA and intraocular pressure elevations analysis 
based on FDA feedback. 
4. Clarification on immunogenicity categories.  


Statistical Analysis Plan for Protocol: IMGN853-0416 
 
 
Confidential and Proprietary 
45 
12. 
REFERENCES 
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