A Phase II Study of MGC018 in Patients With Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer (ES-SCLC)
Phase: PHASE2
Conditions: Extensive-stage Small-cell Lung Cancer
Sponsor: Georgetown University



 
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2 
SPONSOR SIGNATURE PAGE 
Declaration of Sponsor or Responsible Medical Officer 
 
Title: A Phase II Study of Vobramitamab duocarmazine (MGC018) in Patients with Relapsed or 
Refractory Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) 
 
This study protocol was subjected to critical review and has been approved by the Sponsor. The 
information it contains is consistent with the current risk/benefit evaluation of the investigational product 
as well as with the moral, ethical, and scientific principles governing clinical research as set out in the 
Declaration of Helsinki and the guidelines on Good Clinical Practice. 
 
 
_
__________________________________   
___
________ 
Chul Kim, MD, MPH  
                                                  Date 
Lombardi Comprehensive Cancer Center 
Georgetown University Medical Center 
 
 
30-Oct-2024 | 11:48 PDT

 
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3 
TABLE OF CONTENTS 
1. 
BACKGROUND .......................................................................................... 10 
1.1 
Background on Small Cell Lung Cancer (SCLC) ................... 10 
1.2 
Background on the Treatment of Extensive Stage Small Cell 
Lung Cancer (ES-SCLC) ....................................................... 10 
1.3 
Background on B7-H3 ........................................................... 10 
1.4 
Background on MGC018 ....................................................... 11 
1.5 
Study rationale and benefit-risk assessment ......................... 12 
1.5.1 
Study rationale for MGC018 in ES-SCLC with progression 
after prior platinum-based chemotherapy ................................................ 12 
2. 
OBJECTIVES AND ENDPOINTS ............................................................... 14 
2.1 
Primary objective ................................................................... 14 
2.2 
Secondary objectives ............................................................. 14 
2.3 
Exploratory objectives ............................................................ 14 
3. 
STUDY DESIGN ......................................................................................... 14 
3.1 
Description of the study ......................................................... 14 
3.1.1 
Study schema & overview of study design ............................ 14 
3.1.2 
Hypothesis ............................................................................. 15 
3.1.3 
Summary of sample size calculation, study accrual and 
duration 
15 
3.1.4 
PK and ADA data................................................................... 15 
3.1.5 
Tumor biopsies ...................................................................... 17 
3.1.6 
Blood based correlative studies ............................................. 17 
3.1.7 
Safety assessment ................................................................ 18 
3.2 
End of study and length of study ........................................... 18 
3.3 
Rationale for study design ..................................................... 18 
3.3.1 
Rationale for MGC018 dose and schedule ............................ 18 
3.3.2 
Rationale for ORR as primary endpoint ................................. 19 
3.3.3 
Rationale for PK and ADA assessments ............................... 19 
3.3.4 
Rationale for biomarker assessments .................................... 19 
4. 
MATERIALS AND METHODS .................................................................... 19 
4.1 
Patients .................................................................................. 19 

 
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4 
4.1.1 
Inclusion criteria ..................................................................... 19 
4.1.2 
Exclusion criteria.................................................................... 21 
4.2 
Study Treatment .................................................................... 22 
4.2.1 
Study treatment formulation, packaging, and handling .......... 22 
4.2.1.1 MGC018 ............................................................................... 22 
4.2.2 
Study treatment dosage, administration, and compliance ..... 22 
4.2.2.1 MGC018 ............................................................................... 22 
4.2.3 
Dose modification and management of adverse events ........ 23 
4.2.3.1 General notes regarding dose modifications & delays ......... 23 
4.2.3.2 Guidelines for management of suspected MGC018-related 
toxicities 24 
4.2.4 
IMP handling and accountability ............................................ 44 
4.3 
Concomitant therapy .............................................................. 44 
4.3.1 
Prohibited therapy.................................................................. 44 
4.4 
Study assessments ................................................................ 45 
4.4.1 
Informed consent forms (ICFs) .............................................. 45 
4.4.2 
Medical history, concomitant medication, and demographic 
data 
45 
4.4.3 
ECOG performance status .................................................... 45 
4.4.4 
Physical examinations ........................................................... 45 
4.4.5 
Tumor response evaluations ................................................. 46 
4.4.6 
Laboratory, biomarker, and other biological samples ............ 46 
4.5 
Treatment, Patient, and Study Discontinuation ...................... 47 
4.5.1 
Treatment discontinuation ..................................................... 47 
4.5.2 
Patient discontinuation from study ......................................... 48 
4.5.3 
Study discontinuation ............................................................. 49 
4.6 
Multi-institutional trial management ....................................... 49 
4.6.1 
Personnel .............................................................................. 49 
4.6.2 
Patient enrollment .................................................................. 49 
4.6.3 
Data collection and management .......................................... 50 
4.6.4 
Conference calls .................................................................... 50 
4.6.5 
Trial monitoring ...................................................................... 50 
5. 
ASSESSMENT OF SAFETY ....................................................................... 50 

 
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5 
5.1 
Safety plan ............................................................................. 50 
5.1.1 
Risks associated with MGC018 ............................................. 50 
5.2 
Safety parameters and definitions ......................................... 51 
5.2.1 
Adverse events (AEs) ............................................................ 51 
5.2.2 
Serious adverse events (SAEs) ............................................. 51 
5.2.3 
Adverse events of special interest (AESIs) ............................ 52 
5.3 
Methods and timing for assessing and recording safety 
variables ................................................................................ 52 
5.3.1 
Assessment of adverse event ................................................ 52 
5.3.1.1 Diagnosis vs. signs and symptoms ....................................... 53 
5.3.1.2 Deaths .................................................................................. 53 
5.3.1.3 Preexisting medical conditions ............................................. 53 
5.3.1.4 Hospitalizations for medical or surgical procedures ............. 54 
5.3.1.5 Assessment of severity of AEs ............................................. 54 
5.3.1.6 Pregnancies ......................................................................... 55 
5.3.1.6.1 Pregnancies in female patients .................................... 55 
5.3.1.6.2 Pregnancies in female partners of male patients ......... 55 
5.3.1.7 Other special Situations reports ........................................... 55 
5.3.1.8 Product complaints ............................................................... 56 
5.3.2 
Adverse event reporting period .............................................. 56 
5.3.2.1 Post-study adverse events ................................................... 56 
5.3.3 
MedWatch 3500A reporting guidelines .................................. 56 
5.3.4 
Follow-up after adverse events .............................................. 57 
5.3.4.1 Investigator follow-up ........................................................... 57 
5.3.4.2 Sponsor follow-up ................................................................. 57 
5.3.4.3 Follow-up information ........................................................... 57 
5.3.5 
Reporting to regulatory authorities, ethics committees and 
investigators ............................................................................................. 58 
5.4 
Adverse event reporting to Macrogenics ............................... 59 
5.4.1 
Case transmission verification of single case reports ............ 59 
5.5 
Aggregate reports .................................................................. 59 
5.6 
Study close-out ...................................................................... 60 
5.7 
Queries .................................................................................. 60 

 
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5.8 
Signal & risk management ..................................................... 60 
5.9 
Compliance with pharmacovigilance agreement/audit ........... 61 
6. 
STATISTICAL CONSIDERATIONS ............................................................ 61 
6.1 
Determination of sample size ................................................ 61 
6.2 
Planned primary efficacy evaluation & variable ..................... 61 
6.3 
Secondary efficacy variables ................................................. 61 
6.4 
Method of analysis ................................................................. 62 
6.5 
Analysis of exploratory biomarkers ........................................ 62 
7. 
INVESTIGATOR REQUIREMENTS ............................................................ 62 
7.1 
Retention of records .............................................................. 62 
7.2 
Study medical monitoring requirements ................................. 62 
7.2.1 
IRB ......................................................................................... 63 
7.2.2 
Data management and monitoring/auditing ........................... 63 
7.3 
Study medication accountability ............................................ 64 
7.4 
Data collection ....................................................................... 64 
8. 
ETHICAL CONSIDERATIONS .................................................................... 64 
8.1 
Compliance with laws and regulations ................................... 64 
8.2 
Informed consent ................................................................... 65 
8.3 
Institutional review board or ethics committee ....................... 65 
8.4 
Confidentiality ........................................................................ 65 
9. 
STUDY DOCUMENTATION, MONITORING, AND ADMINISTRATION ..... 65 
9.1 
Study documentation ............................................................. 65 
9.2 
Protocol deviations ................................................................ 66 
9.3 
Protocol amendments ............................................................ 66 
10. REFERENCES............................................................................................ 67 
 
 
 
 
 
 

 
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LIST OF TABLES 
Table 1. 
Treatment-related adverse events reported in ≥ 10% of patients13 
Table 2. 
 PK and ADA collection schedule ................................................ 16 
Table 3. 
Administration of first and subsequent MGC018 infusions .......... 22 
Table 4. 
 Dose levels of MGC018 ............................................................. 24 
Table 5. 
Management Guidelines for Pneumonitis ................................... 24 
Table 6. 
Management Guidelines for Elevations in Transaminases ......... 25 
Table 7. 
Management Guidelines for Elevations in Total Bilirubin ............ 27 
Table 8. 
Management Guidelines for Gastrointestinal Events (Diarrhea or Colitis)
 .................................................................................................... 28 
Table 9. 
Management Guidelines for Dermatologic Events ...................... 29 
Table 10. 
Management Guidelines for Nephritis ......................................... 31 
Table 11. 
Management Guidelines for Endocrine Events ........................... 33 
Table 12. Management Guidelines for Blepharitis .............................................. 35 
Table 13. 
 Management Guidelines for Hematologic Events ...................... 36 
Table 14. 
 Management Guidelines for Hematologic EventsError! Bookmark not 
defined. 
Table 15. 
 Management Guidelines for Pleural Effusions ........................... 38 
Table 16. 
 Management Guidelines for Pericardial Effusions ..................... 39 
Table 17. 
 Management Guidelines for Nervous System Events ................ 40 
Table 18. Management Guidelines for Cardiovascular System Events .............. 41 
Table 19. 
 Management Guidelines for Musculoskeletal EventsError! Bookmark 
not defined. 
Table 20. Management Guidelines for Infusion-Related Reactions .................... 42 
Table 21. 
 Adverse Event Severity Grading Scale for Events Not Specifically Listed 
in NCI CTCAE ............................................................................. 54 
 
 
LIST OF APPENDICES 
Appendix 1 
 Study Flowcharts ....................................................................... 69 
Appendix 2 
 Calculation of Creatinine Clearance Using the Cockcroft-Gault Formula
 .................................................................................................... 74 
Appendix 3 
 Anaphylaxis Precautions ............................................................ 75 

 
 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
ADA 
Anti-drug antibody 
ADC 
Antibody-drug conjugate 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AESI 
Adverse event of special interest 
ANC 
Absolute neutrophil count 
B7-H3 
B7 homolog 3 protein 
CFR 
Code of Federal Regulations 
CNS 
Central nervous system 
CTCAE 
Common terminology criteria for adverse effects 
DOR 
Duration of response 
DSMC 
Data safety monitoring committee 
ECOG 
Eastern Cooperative Oncology Group 
EBV 
Epstein Barr Virus 
ES-SCLC 
Extensive stage small cell lung cancer 
EOTV 
End of treatment visit 
FFPE 
Formalin fixed paraffin-embedded 
GCP 
Good clinical practice 
HIPAA 
Health Insurance Portability and Accountability 
HTSR 
Histopathology & Tissue Shared Resource 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
IMP 
Investigational medicinal product 
IRB 
Institutional review board 
IRR 
Infusion related reaction 
LCCC 
Lombardi comprehensive cancer center 
LPLV 
Last patient, last visit 
mCRPC 
Metastatic castration resistant prostate cancer 
MGUH 
MedStar Georgetown University Hospital 
mIg 
Membrane bound immunoglobulin 
MRI 
Magnetic resonance imaging 

 
 
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NGS 
Next generation sequencing 
NSCLC 
Non-small cell lung cancer 
ORR 
Objective response rate 
OS 
Overall survival 
PD-1 
Programmed cell death 1 
PD-L1 
Programmed cell death ligand 1 
PET 
Positron emission tomography 
PFS 
Progression free survival 
PI 
Principal investigator 
PK 
Pharmacokinetic 
RECIST 
Response evaluation criteria in solid tumors 
SAE 
Severe adverse event 
SBRT 
Stereotactic body radiation therapy 
SCLC 
Small cell lung cancer 
SRS 
Stereotactic radiosurgery 
STIAMP 
Suspected transmission of an infectious agent by the study drug 
T3 
Free triiodothyronine 
T4 
Free thyroxine 
TcR 
T-cell antigen receptor 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
VAF 
Variant allele frequency 
WGS 
Whole genome sequencing 
WES 
Whole exome sequencing 
WTS 
Whole transcriptome sequencing 
 
 
 
 
 
 
 
 
 

 
 
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1. 
BACKGROUND 
1.1 
BACKGROUND ON SMALL CELL LUNG CANCER (SCLC) 
Small cell lung cancer (SCLC) an exceptionally aggressive subtype of lung cancer; it accounts for 10-
15% of all lung cancers (Gazdar et al. 2017). SCLC is characterized by early metastases along with 
rapid growth and resistance to treatment. In 2018, there was an estimated 29,514 new cases of SCLC 
with a 5-year survival rate of just 6.9%. About 75% of patients with newly diagnosed SCLC present with 
disseminated disease, with a 5-year survival of only about 3% (Surveillance Research Program, 
National Cancer Institute). 
 
1.2 
BACKGROUND ON THE TREATMENT OF EXTENSIVE STAGE SMALL CELL 
LUNG CANCER (ES-SCLC) 
For extensive stage small cell lung cancer (ES-SCLC), the standard of care frontline treatment has 
generally involved platinum-based chemotherapy with etoposide for several decades. Despite high 
initial response rates of about 65%, patients will predictably experience relapse after chemotherapy 
alone, with median overall survival (OS) of only about 10 months (Rossi et al. 2012). In the last several 
years, immunotherapy has demonstrated clinical activity in ES-SCLC. The phase III IMpower133 trial 
demonstrated that in patients with ES-SCLC, the addition of atezolizumab to standard first-line 
platinum-based chemotherapy improved both PFS (5.2 months vs 4.3 months) and OS (12.9 months vs 
10.3 months) when compared to platinum-based chemotherapy alone (Horn et al. 2018). The CASPIAN 
trial showed similar modest improvements in OS with the addition of the programmed cell death ligand-
1 (PD-L1) inhibitor durvalumab to platinum-based chemotherapy (Paz-Ares et al. 2019). 
Despite these improvements in therapy, the majority of patients will relapse. Outcomes in patients with 
relapsed or refractory ES-SCLC remain poor, with median OS of less than six months. Camptothecins 
such as topotecan are used as second-line therapy, however objective response rates (ORRs) are low 
at about 15% (Garst et al. 2007). The alkylating agent lurbinectedin obtained accelerated FDA approval 
in 2020 for patients with ES-SCLC who had disease progression on or after platinum-based 
chemotherapy. The overall response rate was 33% with median duration of response (DOR) of 5.1 
months (Trigo et al. 2020). For patients with chemotherapy free interval ≥ 90 days, the response rates 
were even greater with ORR of 45% and median PFS of 4.5 months. In patients with chemotherapy 
free interval < 90 days, the ORR was 22% and median PFS of 2.6 months. Despite these recent 
advances, outcomes remain poor, and there is need to develop novel therapeutics for relapsed or 
refractory ES-SCLC.  
 
1.3 
BACKGROUND ON B7-H3 
B7 homolog 3 protein (B7-H3), which is also known as CD276, is a type I transmembrane protein 
encoded on chromosome 15 and is a member of the B7 family of immune check points (Seaman et al. 
2017). The B7 family of cell surface molecules consist of structurally related protein ligands that bind to 
receptors on lymphocytes and regulate immune responses. Activation of T and B lymphocytes is 
initiated by engagement of antigen-specific receptors, T cell antigen receptor (TcR) and membrane 
bound immunoglobulin (mIg) respectively, but additional signals delivered simultaneously to members 
of the CD28 family of receptors by B7 ligands determine the ultimate immune response (Collins et al. 
2005). The B7-H3 pathway is involved in the immune response in various ways, including blocking NK 
mediated lysis and augmenting proinflammatory cytokines. Although B7-H3 mRNA is widely distributed, 
B7-H3 protein expression in normal human tissue is limited, presumably thought to be from the 
negative regulation of B7-H3 protein expression by the microRNA miR-29 (Xu et al. 2009). B7-H3 has 
been implicated in the delivery of both co-stimulatory and co-inhibitory signals (Hofmeyer et al. 2008). 

 
 
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3.1.2 
Hypothesis 
Administration of MGC018 will achieve a clinically meaningful response rate of 25% in patients with 
relapsed or refractory ES-SCLC. 
 
3.1.3 
Summary of sample size calculation, study accrual and duration 
Using the Simon’s optimal two-stage design (Simon, Controlled clinical trials, 1989), we plan to enroll 
up to 17 patients. The null hypothesis that the true response rate is 5% will be tested against a one-
sided alternative. In the first stage, 9 patients will be accrued. If there is no response in these 9 
patients, the study will be stopped. If there is at least one response (including unconfirmed partial 
response) in the first 9 patients, 8 additional patients will be accrued for a total of 17. The null 
hypothesis will be rejected if 3 or more responses are observed in 17 patients. This design yields a type 
I error rate of 4.7% and power of 81.2%, when the true response rate is 25%. Time-to-event data, such 
as DOR, PFS, and OS, will be estimated using the Kaplan-Meier method. Cox proportional hazards 
models will be used to estimate hazard ratios. Safety data will be summarized descriptively. Adverse 
events will be summarized by severity, seriousness, and relationship to the study drug. 
Patients will be enrolled at Georgetown Lombardi Comprehensive Cancer Center (LCCC), Washington 
Hospital Center, John Theurer Cancer Center, and Rutgers Cancer Institute of New Jersey at 
University Hospital. Other sites may be added to the study. Combined expected accrual is 1-2 patients 
per month. With expected required accrual period of 12 months duration. Patients will be followed with 
imaging tumor assessments every 2 cycles assess ORR. Upon progressive disease of unacceptable 
toxicity, patients will be taken off study and monitored every 6 months for two years for survival data. 
 
3.1.4 
PK and ADA data 
Blood samples will be regularly collected and submitted for PK and anti-drug antibody (ADA) assays. 
Support for these assays will be provided by MacroGenics. Total and ADC PK assays as well as ADA 
assays will be performed on the serum. Samples for PK data will be collected pre- and post-infusion as 

 
 
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well as on day 15 of cycles 1 and 2 then pre- and post-infusion for cycles 3 through 5 as well as every 3 
cycles for cycles 6 through 12. ADA assays will be performed on samples collected pre-infusion as well 
as on day 15 of cycle 1 then pre-infusion for cycles 2 through 5 and every 3 cycles for cycles 6 through 
12. PK and ADA testing will be obtained at the EOTV. PK and ADA testing may be performed at the 
time of any IRR.  
Table 2.  
PK and ADA collection schedule  
 
Cycle 
Day 
Timepoint 
Window 
PK: 
Total and 
ADC 
(serum) 
ADA: 
(serum) 
1 
1 
Pre-infusion 
N/A 
X 
X 
1 
1 
End of infusion 
+10 min 
X 
 
1 
15 
Day 15 
N/A 
X 
X 
2 
1 
Pre-infusion 
N/A 
X 
X 
2 
1 
End of infusion 
+10 min 
X 
 
2 
15 
Day 15 
N/A 
X 
 
3, 4, and 5 
1 
Pre-infusion 
N/A 
X 
X 
3, 4, and 5 
1 
End of infusion 
+10 min 
X 
 
6, 9, and 12 
1 
Pre-infusion 
N/A 
X 
X 
6, 9, and 12 
1 
End of infusion 
+10 min 
X 
 
IRRa 
N/A 
N/A 
N/A 
X 
X 
EOTV 
N/A 
EOTV 
N/A 
X 
X 
Note: Actual start of infusion times, EOI times, and PK/ADA sample collection times will be recorded on 
the eCRFs. Do not collect PK samples from infusion port. Pre-infusion PK samples may be collected 
before start of infusion on visit day (dosing day) or day before infusion. When collecting multiple 
samples, collect the PK sample first. 
aPK and ADA samples may be obtained at additional time points in participants who experience signs 
and symptoms of IRR. Samples should be obtained as soon as possible after onset of IRR, if feasible. 
 
 

 
 
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3.1.5 
Tumor biopsies 
A tissue biopsy will be obtained prior to initiation of study treatment with an optional biopsy at the time 
of progression. If biopsy is not considered safe 
and medically feasible by the investigator, the 
patient may be approved for enrollment after 
consultation the principal investigator. In this case, 
we will obtain archival tissue if available. 
Expression of B7-H3 and other immune markers 
on tumor tissue will be assessed using Imaging 
Mass Cytometry (IMC; Fluidigm platform) and 
correlated with treatment outcomes such as ORR, 
PFS, and OS. Imaging Mass Cytometry platform is 
capable of simultaneous detection of up to 40 
protein markers including B7-H3 at subcellular 
resolution in fixed tissues sections. Imaging Mass 
Cytometry is available through the Histopathology 
& Tissue Shared Resource (HTSR) at Georgetown 
Lombardi Comprehensive Cancer Center. 
Samples are analyzed using ilastik and Cell 
Profiler software (Figure 4) for cell mask 
segmentation, allowing to identify individual cells in 
the tissue based on staining of the nuclei (DAPI 
staining) and plasma membrane. This analysis is 
followed by evaluating the expression of the 
markers using HistoCAT software. An optional 
tumor biopsy at the time of disease progression 
will be obtained after radiographic progression 
prior to start of new anti-cancer treatment, if any. 
These samples will enable analysis of tumor tissue 
biomarkers related to resistance, disease 
progression, and clinical benefit of the study 
treatment. If sufficient tissue is available after IMC 
analysis, next generation sequencing (NGS) may 
be performed to understand the correlation 
between genomic findings and response to 
treatment. Please refer to the lab manual for full 
details.  
 
 
 
3.1.6 
Blood based correlative studies 
In collaboration with Dr. Christian Rolfo at the Tisch Cancer Institute at Mount Sinai Health System, we 
plan to analyze extracellular vesicle (EV) B7-H3 expression on day 1 of cycle 1, on day 1 of cycle 3, 
and at the time of progression. Peripheral blood will be collected into EDTA Vacutainer® tubes. Blood 
samples will be centrifuged at 2,000 × g for 15 minutes, and plasma will be isolated and frozen at -
80 °C. Blood samples will be analyzed in a batch. Following the last recommendations of the 
International Society of Extracellular Vesicles (ISEV), EVs will be characterized by nanoparticle tracking 
analysis (NTA), transmission electron microscopy (TEM), and western blot following standardized 
Figure 4. High dimensional data analysis of images of NSCLC tissue 
sample. (A) tSNE (t-distributed stochastic neighbor embedding) plot 
showing multidimensional data. (B) Phenograph clustering analysis 
representing phenotypic similarities between cells. (C) Overlay images 
of MET, VEGF and VISTA on histoCAT. (D) Overlay of the markers 
highlighting phenograph cluster 1 (turquoise). Immune checkpoints 
including B7-H3 (E), and fibroblast/stroma (F). 

 
 
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methodology established at Dr. Rolfo’s laboratory (de Miguel-Perez et al. 2022). The baseline EV 
expression of B7-H3 and the EV B7-H3 dynamics will be correlated with treatment outcomes. Please 
refer to the lab manual for full details. 
 
 
3.1.7 
Safety assessment 
Safety will be closely monitored by assessing for the frequency of severe adverse events and 
unexpected adverse events, including adverse events of special interest (AESIs). Georgetown 
University institutional review board (IRB) and data safety monitoring committee (DSMC), in conjunction 
with the study Principal Investigator (PI), will be responsible for monitoring the safe conduct of this 
study in real time. Regular DSMC meetings will take place approximately every 3 months or more 
frequently and resulting recommendations will be forwarded to the IRB, in addition to the PI (as study 
sponsor). If the DSMC recommends a study change for patient safety or efficacy reasons, it is the 
responsibility of the PI to implement said changes expeditiously. In the unlikely event of disagreement, 
the trial PI, DSMC Chair and LCCC Deputy Director will be responsible for determining a mutually 
agreed upon decision. Should the DSMC recommend trial closure for any reason, the recommendation 
will be reviewed by the LCCC Deputy Director. Authority to close a trial for safety concerns lies with the 
IRB in concert with DSMC and LCCC Deputy Director input. No interim analyses specifically for safety 
are planned as part of this study. 
 
3.2 
END OF STUDY AND LENGTH OF STUDY 
The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the 
required number of events for the final analysis of ORR has occurred or all patients meet one of the 
following criteria: patient has experienced a PFS event, patient has become lost to follow-up, patient 
has withdrawn consent, or patient has completed at least 24 months of follow-up after study treatment 
initiation. The end of the study is expected to occur approximately 1 year after the last patient is 
enrolled. In addition, the principal investigator may decide to terminate the study at any time. The total 
length of the study, from screening of the first patient to the end of the study, is expected to be 
approximately 3 years. 
 
3.3 
RATIONALE FOR STUDY DESIGN 
3.3.1 
Rationale for MGC018 dose and schedule 
MGC018 will be administered at a dose of 2.0 mg/kg every 28 days continuously until completion of 8 
cycles, disease progression, or unacceptable toxicity. The dose was selected on the basis of available 
clinical pharmacokinetics, efficacy, and safety data from the open label, dose escalation CP-MGC018-
01 phase I study. Specifically, the dosing was 3.0 mg/kg every 21 days in the prior phase 1 dose 
escalation study of MGC018 (Shenderov et al. 2021). However, there has been subsequent evidence 
of increased neutropenia and hand-foot syndrome at this dose, and doses of 2.0 mg/kg every 28 days 
and 2.7 mg/kg every 28 days are being investigated in the phase 2 and 3 MGC018 trials. For patients 
who require a dose-reduction, the first reduction would be to 1.5 mg/kg every 28 days and a second 
reduction to 1.0 mg/kg as needed. Please refer to the MGC018 IB for details. 
 
 

 
 
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3.3.2 
Rationale for ORR as primary endpoint 
In this study, the primary endpoint of efficacy will be investigator-assessed ORR as determined by 
RECIST v1.1 with tumor imaging assessments obtained every 2 cycles. As this is a small phase 2 
study to evaluate the efficacy of a novel therapy in a treatment refractory patient population, ORR was 
chosen in order to make an early determination for signal of efficacy that could then be used to warrant 
larger scale clinical trials powered for OS/PFS or, given the modified Simon 2-stage design, early study 
closure for futility if no efficacy signal is observed. Given the low historical ORR to chemotherapy in 
relapsed or refractory patients with ES-SCLC, a rapid estimation of response utilizing ORR will also be 
important as it will enable patients with robust functional status who experience disease progression on 
this trial seek additional treatments either in a clinical trial or standard of care setting.  
 
3.3.3 
Rationale for PK and ADA assessments 
The optimal dosing of MGC018 is still being determined. While the dose 3.0 mg/kg every 21 days was 
used in the phase 1 trial, this dose was subsequently found to be associated with increased rates of 
neutropenia and hand-foot syndrome. The use of 2.0 mg/kg every 28 days are currently being 
investigated in phase 2 and 3 trials. Collection of PK and ADA data for patients receiving 2.7 mg/kg 
every 28 days, as well as for those who require a dose-reduction to 2.0 mg/kg every 28 days, will be 
useful in elucidating the optimal regimen. 
 
3.3.4 
Rationale for biomarker assessments 
Early clinical studies have shown that efficacy of MGC018 in patients with non-small cell lung cancer 
(NSCLC) and metastatic castration resistant prostate cancer (mCRPC) can be seen across varying 
levels of B7-H3 expression (Shenderov et al. 2021). This is suspected to be likely from bystander killing 
of neighboring tumor cells which has been demonstrated in vivo (Scribner et al. 2020). However, this 
has not been studied in ES-SCLC, and current clinical data regarding correlation between MGC018 
efficacy and B7-H3 expression is still early. In this study, we will assess expression of B7-H3 on tumor 
tissue obtained prior to study initiation and correlate with treatment outcomes. Furthermore, blood-
based biomarkers including exosome analysis in collaboration with Dr. Christian Rolfo at the Tisch 
Cancer Institute at Mount Sinai Health System will be analyzed and correlated with treatment 
outcomes. 
 
4. 
MATERIALS AND METHODS 
4.1 
PATIENTS 
Approximately 17 patients with relapse or refractory ES-SCLC will be enrolled in this study. 
 
4.1.1 
Inclusion criteria 
Patients must meet the following criteria for study entry: 
1) Age ≥ 18 years at time of signing ICF 
2) Ability to comply with the study protocol, in the investigator’s judgment. 

 
 
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3) Histologically or cytologically confirmed advanced small cell lung cancer that is not amenable to 
definitive therapy. Patients with EGFR-mutant NSCLC that has transformed to SCLC will be 
allowed.  
4) Disease progression during or following treatment with platinum-based chemotherapy.  
a) Patients could have received any number of therapies for relapsed or progressive disease.  
5) Measurable disease per RECIST v1.1 
6) ECOG Performance Status of 0-2  
7) Adequate hematologic and end-organ function, defined by the following laboratory test results, 
obtained within 14 days prior to initiation of study treatment: 
a) ANC ≥ 1.0 × 109/L (1000/µL) without granulocyte colony-stimulating factor support 
b) Platelet count ≥ 100 × 109/L (100,000/µL) without transfusion  
c) Hemoglobin ≥ 80 g/L (8 g/dL) 
(1) Patients may be transfused to meet this criterion. 
d) AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following 
exceptions: 
(1) Patients with documented liver metastases: AST and ALT ≤ 5 × ULN 
(2) Patients with documented liver or bone metastases: ALP ≤ 5 × ULN 
e) Serum bilirubin ≤ 1.5 × ULN with the following exception: 
(1) Patients with known Gilbert disease: serum bilirubin ≤ 3 × ULN 
f) Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula, see Appendix 
2) 
g) For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 × ULN 
NOTE: Screening labs that are performed outside the 14-day window for eligibility criteria may be 
repeated on C1D1 to verify the subject meets eligibility requirements. 
8) Ability to understand and the willingness to sign a written informed consent document.  
9) Availability of pre-treatment tumor tissue via a biopsy. If biopsy is not considered safe and medically 
feasible by the Investigator, the patient may be approved for enrollment after consultation with the 
Principal Investigator.  
10) For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual 
intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as 
defined below: 
(1) Women must remain abstinent or use contraceptive methods with a failure rate of 
< 1% per year during the treatment period and for 6 months after the final dose of study 
treatment. Women must refrain from donating eggs during this same period. 
(2) A woman is considered to be of childbearing potential if she is postmenarchal, has not 
reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no 
identified cause other than menopause), and has not undergone surgical sterilization 
(removal of ovaries and/or uterus). The definition of childbearing potential may be 
adapted for alignment with local guidelines or requirements. 

 
 
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(3) Examples of contraceptive methods with a failure rate of < 1% per year include bilateral 
tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-
releasing intrauterine devices, and copper intrauterine devices. 
(4) The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., 
calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not 
adequate methods of contraception. 
11) For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive measures, and agreement to refrain from donating sperm, as defined below: 
(1) With a female partner of childbearing potential who is not pregnant, men who are not 
surgically sterile must remain abstinent or use a condom plus an additional contraceptive 
method that together result in a failure rate of < 1% per year during the treatment period 
and for 90 days after the final dose of MGC018. Men must refrain from donating sperm 
during this this same period. 
(2) With a pregnant female partner, men must remain abstinent or use a condom during the 
treatment period and 90 days after the final dose of MGC018 to avoid potential exposure 
to the embryo. 
(3) The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., 
calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not 
adequate methods of contraception. 
 
ii) Exclusion criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
1) Patients with treated CNS metastases are eligible if they are symptomatically stable while off 
steroid therapy for a minimum of 7 days 
2) Symptomatic leptomeningeal disease. Patients with asymptomatic treated or untreated 
leptomeningeal disease could be enrolled provided that all other protocol-defined criteria are met.  
3) Patient who are receiving any other investigational agents 
4) Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study 
treatment, or anticipation of need for a major surgical procedure during the study 
5) Diagnosis of another malignancy. However, patients with prior or concurrent malignancy whose 
natural history or treatment does not have the potential to interfere with the safety or efficacy 
assessment of the investigational regimen are eligible for this trial. 
6) Evidence of pleural and/or pericardial effusion. A small and/or asymptomatic effusion is not 
exclusionary. 
7) Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding 
that, in the view of the investigator, contraindicates the use of an investigational drug, may affect 
the interpretation of the results, or may render the patient at high risk from treatment complications. 
8) Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 6 
months after the final dose of study treatment. 
 

 
 
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4.2 
STUDY TREATMENT 
The investigational medicinal product (IMP) for this study is MGC018. 
4.2.1 
Study treatment formulation, packaging, and handling 
4.2.1.1 
MGC018 
MGC018 will be supplied by Macrogenics as sterile liquid at a nominal protein concentration of 10 
mg/mL in a single-use glass vial containing 93 mg/9.3mL MGC018. The drug product is formulated in a 
solution of 0.46.mg/mL L-histidine, 1.47 mg/mL L-histidine hydrochloride monohydrate, 90 mg/mL 
sucrose, and 0.1 mg/mL polysorbate 80, pH 5.7. For further information on the MGC018 formulation, 
refer to the MGC018 investigator’s brochure (IB). 
 
4.2.2 
Study treatment dosage, administration, and compliance 
The treatment regimens are summarized in Section 3.1.1. 
Any overdose or incorrect administration of MGC018 should be noted in the patient’s medical records 
and reported according to Sections 5.4 and 5.5. Adverse events associated with an overdose or 
incorrect administration of any of the study treatments should be recorded in the patient’s medical 
records and appropriate eCRF.  
Guidelines for dosage modification, treatment interruption or discontinuation for patients who 
experience adverse events are provided in Section 4.3.3 and Appendix 4. Dose modification of all study 
drugs (MGC018) will not be permitted. 
 
4.2.2.1 
MGC018 
MGC018 will be administered by IV infusion at a dose of 2.0 mg/kg on Day 1 of each 28-day cycle until 
completion of cycle 8, unacceptable toxicity, or loss of clinical benefit as determined by the investigator 
after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), 
and clinical status (see Section 3.1.1 for details). For subjects weighing ≥ 100 kg the doses will be 
based on 100 kg for these subjects. To decrease the frequency and severity of palmar-plantar 
erythrodysesthesia (PPE) and effusions, prednisone 40 mg will be given twice daily for three days of 
each cycle starting the evening after each infusion for a total of 6 doses. In addition, patients will be 
provided with a strong or moderate-strength topical steroid cream to be applied as prescribed to the 
hands and soles prophylactically for the first 12 weeks of therapy. 
Administration of MGC018 will be performed in a monitored setting where there is immediate access to 
trained personnel and adequate equipment and medicine to manage potentially serious reactions. For 
anaphylaxis precautions, see Appendix 3. MGC018 infusions will be administered per the instructions 
outlined in Table 3. 
 
Table 3. 
Administration of first and subsequent MGC018 infusions 
Study Drug 
First Infusion 
Subsequent Infusions 
MGC018 
infusion 
• 
Premedication with acetaminophen 
(650mg to 1000 mg), 
diphenhydramine 50 mg PO or IV, 
famotidine 40 mg PO or 20 mg IV, 
and corticosteroid (e.g 
• 
If the patient experienced an infusion-
related reaction (IRR) with any 
previous infusion, additional 
premedication may also be 
considered.  

 
 
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Refer to the pharmacy manual for detailed instructions on drug preparation, storage, and 
administration. 
 
4.2.3 
Dose modification and management of adverse events 
4.2.3.1 
General notes regarding dose modifications & delays 
Reasons for dose delays, supportive measures taken, and subsequent outcome will be documented in 
the patient's chart and recorded on the eCRF. The severity of adverse events will be graded according 
to the NCI CTCAE v5.0 grading system. 
dexamethasone 4 mg IV or 
equivalent) 
• 
Vital signs (pulse rate, respiratory 
rate, blood pressure, and 
temperature) should be measured 
within 60 minutes prior to the 
infusion. 
• 
MGC018 should be infused over 60 
minutes. Up to 10 additional minutes 
of infusion time is permitted to allow 
for flushing the IV line. 
• 
If clinically indicated, vital signs 
should be measured every 
15 (± 5) minutes during the infusion. 
• 
Patients should be informed about 
the possibility of delayed post-
infusion symptoms and instructed to 
contact their study physician if they 
develop such symptoms. 
• 
Vital signs should be measured 
within 60 minutes prior to the 
infusion. 
• 
MGC018 should be infused over 
60 minutes (± 10 minutes) if the 
previous infusion was tolerated 
without an IRR, or 60 (± 15) minutes 
if the patient experienced an IRR with 
the previous infusion. 
• 
If clinically indicated, vital signs 
should be measured during the 
infusion and at 30 (± 10) minutes 
after the infusion. 
Observation 
period after 
infusion of 
MGC018 
• 
After the infusion of MGC018, the 
patient begins a 60-minute 
observation period. 
• 
Vital signs should be recorded at 30 
+/-10) minutes after the infusion of 
MGC018. 
• 
Patients will be informed about the 
possibility of delayed post-infusion 
symptoms and instructed to contact 
their study physician if they develop 
such symptoms. 
• 
If the patient tolerated the previous 
MGC018 infusion well without 
infusion-associated adverse events, 
no observation period is needed. 
• 
If the patient experienced infusion-
associated adverse events in the 
previous infusion, an observation 
period of 60 minutes should occur. 
• 
If clinically indicated, vital signs should 
be recorded at 30 (+/-10) minutes 
after the infusion of MGC018. 

 
 
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• 
When several toxicities with different grades of severity occur at the same time, appropriate 
action should be made according to the highest grade observed. 
• 
If, in the opinion of the investigator, a toxicity is considered to be due solely to MGC018 and is 
of sufficient grade to warrant treatment delay, therapy should be delayed and omitted until 
resolution of toxicity. 
• 
If, in the opinion of the investigator, a toxicity attributed to MGC018 is of sufficient grade to 
warrant permanent discontinuation of therapy, therapy should be permanently discontinued. 
For patients who require a dose-reduction, the first reduction would be to 1.5 mg/kg every 28 days with 
a second reduction to 1.0 mg/kg every 28 days, as needed (Table 4). 
 
Table 4.  
Dose levels of MGC018 
Dose levels 
MGC018 
Level 1 (starting dose) 
2.0 mg/kg Q4W 
Level -1  
1.5 mg/kg Q4W 
Level -2 
1.0 mg/kg Q4W 
 
4.2.3.2 
Guidelines for management of suspected MGC018-related toxicities 
Criteria for treatment modification and guidelines for the management of toxicities are summarized 
below. Generally, temporary suspension of MGC018 must occur if a patient experiences a serious 
adverse event or a grade 3 or 4 non-serious adverse event assessed by the investigator as related to 
MGC018. If the event resolves to grade ≤ 1, MGC018 may be restarted at the same dose level. If 
MGC018 is delayed due to toxicity for > 8 weeks beyond when the next dose should have been given, 
the patient must be permanently discontinued from MGC018. 
 
PULMONARY EVENTS 
Immune-mediated pulmonary events are a potential risk with MGC018. Patients will be assessed for 
pulmonary signs and symptoms throughout the study and will have computed tomography (CT) scans 
of the chest performed at every tumor assessment.  
All pulmonary events should be thoroughly evaluated for other commonly reported etiologies such as 
pneumonia or other infection, lymphangitic carcinomatosis, pulmonary embolism, heart failure, chronic 
obstructive pulmonary disease, or pulmonary hypertension. Management guidelines for pulmonary 
events are provided in Table 5. 
 
Table 5. 
Management Guidelines for Pneumonitis 

 
 
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Event 
Management 
Grade 1  
• Continue MGC018 and monitor closely. 
• Re-evaluate on serial imaging. 
• No specific therapy required 
Grade 2 
• Hold MGC018 
• Consider treatment with corticosteroids equivalent to 1−2 mg/kg/day oral 
prednisone or equivalent divided twice daily 
• Taper corticosteroids over 4 weeks or as clinically indicated 
• Resume MGC018 administration at next scheduled dose if pneumonitis 
resolves to grade 1 or baseline within 5 days with or without treatment. On 
resuming MGC018, reduce dose by one dose level.  
• Discontinue MGC018 after second occurrence 
Grade 3 or 4 
• Permanently discontinue MGC018 
• Hospitalize 
• Referral for pulmonary consult with diagnostic evaluation with chest X-ray 
and CT scan. 
• Initiate treatment with IV corticosteroids, suggest methylprednisolone at 2 to 
4 mg/kg/day divided twice daily. Higher doses may be used in consultation 
with the sponsor’s medical monitor. 
• If event does not improve within 3 to 5 days after initiating corticosteroids, 
consider adding an immunomodulatory agent. 
  
HEPATIC EVENTS 
Immune-mediated hepatic events are a potential risk with MGC018. 
Immune-related hepatitis has been associated with the administration of MGC018. Eligible patients 
must have adequate liver function, as manifested by measurements of total bilirubin and hepatic 
transaminases, and liver function will be monitored throughout study treatment. 
Patients with right upper-quadrant abdominal pain and/or unexplained nausea or vomiting should have 
liver function tests (LFTs) performed immediately and reviewed before administration of the next dose 
of study drug. 
For patients with elevated LFTs, concurrent medication, viral hepatitis, and toxic or neoplastic etiologies 
should be considered and addressed, as appropriate. 
 
Table 6. 
Management Guidelines for Elevations in Transaminases 
Event 
Management 

 
 
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Grade 1 
• 
Continue MGC018. 
• 
No specific therapy required 
• 
Monitor LFTs until values resolve to within normal limits or to baseline 
values.  
Grade 2 
• 
Rule out viral and other etiologies 
• 
Consider imaging such as ultrasound, or CT scan 
• 
Hold MGC018 
• 
Consider starting oral prednisone 1 mg/kg per day 
• 
If improvement to grade 1 or baseline does not occur within 72 hours with 
oral steroids, consider IV steroids (i.e methylprednisolone 1-2 mg/kg/day 
divided twice daily) 
• 
Resume MGC018 at next scheduled dose if no more than one dose of 
MGC018 was missed 
• 
If improvement to grade 1 or baseline does not occur within 21 days, 
discontinue MGC018 
• 
No dose reduction required after first occurrence 
• 
On resuming MGC018, reduce dose by one dose level after second and 
third occurrences 
• 
Discontinue MGC018 after fourth occurrence 
Grade 3 
• 
Hold MGC018 
• 
Begin IV steroids methylprednisolone 2 mg/kg/day divided twice daily and 
if no response within 3 to 5 days, consider adding additional immune 
suppression therapy (e.g. mycophenolate). 
• 
Monitor liver functions tests at least twice weekly (or more frequently as 
clinically appropriate) until transaminases have returned to grade 1. 
• 
For elevations in transaminases >8 x ULN, permanently discontinue 
MGC018. 
• 
If elevation does not improve to grade 2 within 10 days and to grade 1 
within 21 days, discontinue MGC018. 
• 
Resume MGC018 if following conditions are met: 
o Lab elevations improve to grade 2 within 10 days and to grade 1 
within 21 days 
o Steroids have been tapered to ≤10 mg per day or prednisone or 
equivalent 
o On resuming MGC018, LFT’s will be evaluated at least once per 
week for 3 consecutive weeks 
• 
On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 

 
 
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• 
Discontinue MGC018 after third occurrence 
Grade 4 
• 
Treat as grade 3 as above 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 
 
Table 7. 
Management Guidelines for Elevations in Total Bilirubin 
Event 
Management 
Grade 1 
• Continue MGC018 
• No specific therapy required 
Grade 2 
• 
Hold MGC018 until improvement to ≤ grade 1 
• 
Rule out viral and other etiologies 
• 
Consider imaging studies such as ultrasound or CT scan, and liver biopsy 
to ascertain etiology of liver dysfunction 
• 
Consider oral prednisone 1 mg/kg 
• 
If improvement to ≤ grade 1 does not occur within 21 days, discontinue 
MGC018 and begin oral steroids 
• 
No dose reduction required after first occurrence 
• 
On resuming MGC018, reduce dose by one dose level after second and 
third occurrences 
• 
Discontinue MGC018 after fourth occurrence 
Grade 3 
• Hold MGC018 
• For elevations in total bilirubin >5 x ULN  
o Permanently discontinue MGC018 and initiate IV steroids, i.e 
methylprednisolone 2 mg/kg/day divided twice daily 
o If no response to corticosteroids within 3 to 5 days, consider adding 
additional immune suppression therapy (e.g. mycophenolate) 
o Monitor liver function testing at least twice weekly (or more frequently 
as clinically appropriate) until total bilirubin has returned to grade 1 or 
baseline 
• For elevation in total bilirubin >3 but ≤ 5 times ULN 
o Begin IV steroids, i.e methylprednisolone at 2 mg/kg/day divided twice 
daily.  
o Consider additional immune suppression as above if no response to 
corticosteroids within 3 to 5 days 

 
 
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GASTROINTESTINAL EVENTS 
Immune-mediated colitis has been associated with administration of MGC018. 
Management guidelines for diarrhea or colitis are provided in Table 8. 
All events of diarrhea or colitis should be thoroughly evaluated for other more common etiologies. For 
events of significant duration or magnitude or associated with signs of systemic inflammation or acute-
phase reactants (e.g., increased C-reactive protein, platelet count, or bandemia): Perform 
sigmoidoscopy (or colonoscopy, if appropriate) with colonic biopsy.  
 
Table 8. 
Management Guidelines for Gastrointestinal Events (Diarrhea or Colitis) 
o Monitor liver function testing at least twice weekly (or more frequently 
as clinically appropriate) until total bilirubin has returned to grade 1 or 
baseline. 
• Resume MGC018 if: 
o Total bilirubin elevations improve to ≤ grade 2 within 7 days and 
improve to ≤ grade 1 or baseline within 21 days 
o Steroids have been tapered to ≤10 mg per day of prednisone or 
equivalent 
o On resuming MGC018, monitor liver function testing at least once per 
week for 3 consecutive weeks 
• On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 
• Discontinue MGC018 after third occurrence 
Grade 4 
• 
Treat as grade 3 elevation 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 
Event 
Management 
Diarrhea or colitis, 
Grade 1 
• Continue MGC018 
• Initiate symptomatic treatment. 
• Closely monitor the diarrhea until resolution 
Diarrhea or colitis, 
Grade 2 
• Hold MGC018 
• On resolution to grade 1 or baseline, resume MGC018 without dose 
reduction 
• Increase frequency of monitoring until resolution 
• Initiate symptomatic treatment. 

 
 
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DERMATOLOGIC EVENTS 
Immune-related dermatologic events are a potential risk with MGC018. Management guidelines for 
dermatologic events are provided in Table 9. Patients should limit sun exposure and apply broad 
spectrum sunscreen to exposed skin when outdoors. 
For palmar-plantar erythrodysesthesia, hold MGC018 until toxicity resolves to ≤ grade 1. MGC018 may 
be resumed with MGC018 decrease of one dose level. Discontinue MGC018 if patient does not recover 
to ≤ grade 1 within 28 days. 
 
Table 9. 
Management Guidelines for Dermatologic Events 
o Loperamide and or diphenoxylate/atropine 
o Low dose steroids, if clinically indicated 
o Consider management or prolonged grade 2 event lasting more than 5 
to 7 days or relapsed diarrhea as grade 3 diarrhea (below) 
Diarrhea or colitis, 
Grade 3 
• 
Hold MGC018. Hospitalize patient promptly for further evaluation and 
management including the following: 
o Bowel rest 
o IV fluid with close monitoring of fluid and electrolyte status 
o Consider imaging to rule out bowel obstruction or perforation 
o Consideration of colonoscopy as appropriate 
o Empiric immune suppression with IV corticosteroids using 
methylprednisolone at 2 mg/kg/day (or equivalent) divided twice daily. As 
tolerated steroids may be converted to oral corticosteroids and tapered 
as appropriate guided by patient’s clinical status 
o For patients who do not respond to corticosteroids, additional 
immunosuppression with anti-TNF alpha antibodies (i.e infliximab) 
should be considered. 
• 
If it is determined there is no colitis and an alternative cause of diarrhea is 
found, consider restarting MGC018 if diarrhea resolves to ≤ grade 1 within 
21 days 
• 
On resuming MGC018, reduce dose by one dose level after first and second 
occurrences 
• 
Discontinue MGC018 after third occurrence 
Diarrhea or colitis, 
Grade 4 
• 
Treat as grade 3 
• 
On resuming MGC018 reduce dose by two dose levels after first occurrence 
• 
Discontinue MGC018 after second occurrence 
  
Event 
Management 

 
 
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Dermatologic event, 
Grade 1 
• For dry skin, consider application of moisturizers as needed to affected area 
• Symptomatic treatment with low dose topical corticosteroids 
(betamethasone 0.1% or hydrocortisone 1%) or antihistamines 
• Persistent grade 1 or 2 rash should be managed with higher dose topical 
corticosteroids and/or oral prednisone (1 to 2 mg/kg/day) if there is not 
improvement with topical therapies or the rash is associated with other 
dermal toxicities such as pruritis. 
• Evaluate for use of concomitant medications and herbal supplements that 
may exacerbate skin toxicity. 
Dermatologic event, 
Grade 2 
• 
Treat as grade 1 
• 
No dose reduction required after first occurrence 
• 
On resuming MGC018, reduce dose by one dose level after second and 
third occurrences 
• 
Discontinue MGC018 after fourth occurrence 
Dermatologic event, 
Grade 3 
• 
Hold MGC018 
• 
Initiate oral corticosteroids (oral prednisone 1 to 2 mg/kg/day) 
• 
Evaluate participant use of concomitant medications and herbal 
supplements that may exacerbate skin toxicity 
• 
Consider obtaining skin biopsy if SJS or TEN is suspected. If possible, 
refer to specialized care center for clinical management. Cyclosporine 
and/or IV immunoglobulin may be considered for management of SJS or 
TEN. 
• 
Resume MGC018 at next scheduled dose if: 
• 
Skin toxicity resolves to ≤ grade 1 or baseline within 21 days with maximal 
supportive care 
• 
Discontinue study drugs if skin toxicity does not resolve to ≤ grade 1 or 
baseline within 21 days, or for any grade SJS or TEN of any duration. 
• 
On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 
• 
Discontinue MGC018 after third occurrence 
Dermatologic event, 
Grade 4 
• 
Initiate oral corticosteroids (oral prednisone 1 to 2 mg/kg/day) 
• 
Evaluate patient for use of concomitant medications or herbal 
supplements that may exacerbate skin toxicity 
• 
Consider obtaining a skin biopsy if possible diagnosis of SJS or TEN. If 
possible, refer to specialized care center for clinical management. 
Cyclosporine and/or IV immunoglobulin may be considered for 
management of SJS or TEN. 

 
 
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SJS=Stevens-Johnson Syndrome, TEN=toxic epidermal necrolysis 
 
RENAL EVENTS 
Immune-related nephritis is a potential risk with MGC018. Eligible patients must have adequate renal 
function. Renal function, including serum creatinine, should be monitored throughout study treatment. 
Patients with abnormal renal function should be evaluated and treated for other more common 
etiologies (including prerenal and postrenal causes, and concomitant medications such as non-steroidal 
anti-inflammatory drugs). 
Patients with signs and symptoms of nephritis, in the absence of an identified alternate etiology, should 
be treated according to the guidelines in Table 10. 
 
Table 10. 
Management Guidelines for Nephritis  
Event 
Management 
Nephritis, Grade 1 
• Continue MGC018 
• No specific therapy required 
• Close monitoring of renal function  
Nephritis, Grade 2 
• 
Hold MGC018 
• 
Consider nephrology consultation and renal biopsy to confirm interstitial 
nephritis. 
• 
Consider initiating treatment with corticosteroids equivalent to 
1−2 mg/kg/day oral prednisone per day, dose divided twice daily.  
• 
Taper corticosteroids over 4 weeks or as clinically indicated. 
• 
Resume MGC018 at next scheduled dose if nephritis resolves to ≤ grade 
1 within 21 days with or without treatment 
• 
No dose reduction required after first occurrence 
• 
On resuming MGC018, reduce dose by one dose level after second and 
third occurrences 
• 
Discontinue MGC018 after fourth occurrence 
• 
Consideration should be given to start IV corticosteroids 
(methylprednisolone 1 to 2 mg/kg/day) for grade 4 dermatologic toxicities 
with tapering on resolution to <grade 2 over 30 days. 
• 
If SJS or TEN are confirmed, permanently discontinue MGC018 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 

 
 
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Nephritis, Grade 3 
• 
Consider hospitalization, nephrology consultation, and renal biopsy to 
confirm interstitial nephritis. 
• 
Initiate treatment with corticosteroids equivalent to 2−4 mg/kg/day IV 
methylprednisolone divided twice daily. Taper corticosteroids over 4 
weeks or as clinically indicated. 
• 
On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 
• 
Discontinue MGC018 after third occurrence 
Nephritis, Grade 4 
• 
Treat as grade 3 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 
 
ENDOCRINE EVENTS 
Endocrine events are a potential risk with MGC018. 
Thyroid disorders may occur at any time during treatment with MGC018. Monitor participants for 
changes in thyroid function per protocol and as indicated based on clinical evaluation and for clinical 
signs and symptoms of thyroid disorders. Isolated hypothyroidism may generally be managed with 
replacement therapy without treatment delay and without corticosteroids. 
Management guidelines for endocrine events are provided in Table 11.  
 
 

 
 
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Table 11. 
Management Guidelines for Endocrine Events 
Event 
Management 
Hyperthyroidism, 
Grade1 
• Continue MGC018 
• No specific therapy required 
Hyperthyroidism, 
Grade 2 
• 
Hold MGC018 
• 
Consider starting oral corticosteroid therapy.  
• 
Short course of corticosteroid such as methylprednisolone 1 to 2 mg/kg IV 
(or equivalent) divided twice daily. 
• 
Resume MGC018 if corticosteroid if corticosteroid dose is reduced to ≤ 10 
mg prednisone or equivalent per day and stable on hormone replacement 
therapy (if necessary). 
• 
No dose reduction required after first occurrence 
• 
On resuming MGC018, reduce dose by one dose level after second and 
third occurrences 
• 
Discontinue MGC018 after fourth occurrence 
Hyperthyroidism, 
Grade 3 
• 
Hold MGC018 
• 
Consider hospitalization and consulting endocrinologist 
• 
Begin IV corticosteroids such as methylprednisolone 2 to 4 mg/kg IV (or 
equivalent) divided twice daily. 
• 
Initiate hormonal replacement therapy as necessary 
• 
Consider restarting MGC018 with complete resolution or stable on 
hormone replacement therapy within 28 days and if corticosteroid dose is 
reduced to ≤ 10 mg prednisone or equivalent per day. 
• 
On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 
• 
Discontinue MGC018 after third occurrence 
Hyperthyroidism, 
Grade 4 
• 
Treat as grade 3 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 
 
Event 
Management 
Hypophysitis, 
 Grade 1 
• No specific therapy required 
• Continue MGC018 
Hypophysitis, 
• Hold MGC018 

 
 
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OCULAR EVENTS 
Ocular toxicity, including, but not limited to, dry eye, photophobia or blurry vision have been observed in 
participants treated with antibody drug conjugates, and could occur at any time during treatment with 
MGC018.  Management guidelines for ocular events are provided in Table 12. 
 
 
Grade ≥ 2 
• Consult endocrinologist 
• Consider hospitalization 
• Consider short course of high dose IV corticosteroids e.g. 
methylprednisolone 2 to 4 mg/kg/day or equivalent divided twice daily. 
• Initiate hormonal replacement as indicated 
• Study drug may be resumed as allowed by protocol when: 
• 
Endocrinopathy is controlled with appropriate replacement therapy 
• 
Corticosteroid dose reduced to ≤ 10 mg prednisone or equivalent per 
day. 
• Brain MRI recommended 
MRI = magnetic resonance imaging 
  

 
 
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Table 12. Management Guidelines for Blepharitis 
Event 
Management 
Blepharitis, Grade 1  • No specific therapy required. 
• Daily cleansing with warm, clean cloth. Apply lubricating eye drops 
• Patient referral to ophthalmologist is strongly recommended. 
• Initiate treatment with topical corticosteroid eye drops and topical 
immunosuppressive therapy. 
• If symptoms persist, treat as a Grade 2 event. 
Blepharitis, Grade 2 
• Hold MGC018 
• Consider topical/ocular corticosteroids, antihistamine, artificial tears 
• Resume MGC018 if resolved to ≤ grade 1 within 28 days and discontinue 
MGC018 if symptoms last > 28 days 
• On resuming MGC018, if symptoms lasted > 14 days, reduce dose by one 
dose level 
Blepharitis, Grade 3 
• Hold MGC018 
• Consider referral to ophthalmologist. 
• Consider topical/ocular and/or systemic corticosteroids 
• Resume MGC018 if resolved to ≤ grade 1 within 28 days and discontinue 
MGC018 if symptoms last > 28 days 
• On resuming MGC018, reduce dose by one dose level 
Blepharitis, Grade 4 
• Permanently discontinue MGC018 
• Consult ophthalmology within 24 hours 
• Treat as for grade 3 and as appropriate for life-threatening symptoms 
  
 
HEMATOLOGIC EVENTS 
Blood counts should be monitored to determine if dose modification is needed. Consider monitoring 
CBC bi-weekly or weekly based on the participant’s medical history and incidence of myelosuppressive 
AE’s during study drug administration. 
Blood counts will be performed in case of fever (a measured temperature of 100.4 F or greater) or 
evidence of infection. Neutropenic complications should be managed promptly with antibiotic support 
and use of G-CSF according to current ASCO guidelines for use of white blood cell growth factors. 
Consider transfusion of platelets for thrombocytopenia. Use of anticoagulants and platelet inhibitors 
should be held until thrombocytopenia resolves. 
Anemia should be evaluated and treated for other underlying etiology e.g. iron or vitamin B12 
deficiency, bleeding, and renal insufficiency. Consider transfusion of red blood cells or whole blood for 

 
 
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anemia. Caution is recommended in patients with ≥ grade 2 anemia, with appropriate measures taken 
as clinically indicated. Patients will be supported appropriately by the treating physician. 
No specific treatment or drug holds are required for lymphopenia, regardless of CTCAE grade, unless 
associated with opportunistic infection. If the patient develops an opportunistic infection with concurrent 
lymphopenia, MGC018 should be delayed until resolution of lymphopenia and the opportunistic 
infection 
Management guidelines for hematologic events are provided in Table 13. 
Table 13. 
 
Management Guidelines for Hematologic Events  
Event 
Management 
Neutropenia,  
Grade 1 or 2 
• No specific therapy required 
• MGC018 should not be given to participants with neutrophil counts ≤ 1500 
cells/mm3 
• Consider dose reduction of MGC018  
Neutropenia,  
Grade 3 
• 
Hold MGC018 until recovery to ≤ grade 1 
• 
Monitor neutrophil counts weekly until recovery to ≤ grade 1 
• 
Discontinue MGC018 if not recovered to ≤ grade 1, within 21 days 
• 
Restart MGC018 if recovered to ≤ grade 1 within 21 days. 
• 
On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 
• 
Discontinue MGC018 after third occurrence 
Neutropenia,  
Grade 4  
• 
Hold MGC018 until recovery to ≤ grade 1 
• 
Monitor neutrophil counts weekly until recovery to ≤ grade 1 
• 
Discontinue MGC018 if not recovered to ≤ grade 1, within 21 days 
• 
Restart MGC018 at one or two level dose reduction if recovered to ≤ 
grade 1 within 21 days. 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 
Thrombocytopenia,  
Grade 1  
• No specific therapy required 
• Consider dose reduction of MGC018  

 
 
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Thrombocytopenia,  
Grade 2 or 3 
• Hold MGC018 until recovery to ≤ grade 1 
• Monitor platelet counts weekly until recovery to ≤ grade 1 
• Restart MGC018 with one level dose reduction if recovered to ≤ grade 1 
• Reduce dose by one dose level on resumption after second and third 
occurrences 
• Discontinue MGC018 after fourth occurrence 
• Discontinue MGC018 if not recovered to ≤ grade 1 within 21 days. 
Thrombocytopenia,  
Grade 4 
• 
Hold MGC018 until recovery to ≤ grade 1 
• 
Monitor platelet counts weekly until recovery to ≤ grade 1 
• 
Restart MGC018 with one or two level dose reduction if recovered to ≤ 
grade 1 
• 
Discontinue MGC018 if not recovered to ≤ grade 1 within 21 days. 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 
Anemia, Grade 1 
• No specific therapy required  
Anemia, Grade 2 
• Consider iron replacement therapy, erythropoiesis stimulating agent  
Anemia,  
Grade 3 
• Consider iron replacement therapy, erythropoiesis stimulating agent 
• Consider transfusion if symptomatic 
• Consider holding MGC018 until recovery to ≤ grade 2 
• Dose reduction of one dose level for ≥ 2 events of grade 3 anemia 
• Discontinue MGC018 after fourth occurrence 
Anemia,  
Grade 4 
• Transfuse with whole blood or packed red blood cells 
• Permanently discontinue MGC018 for grade 4 anemia that persists despite 
intervention. 
 
PLEURAL AND PERICARDIAL EFFUSIONS 
Supportive care per institutional practice should be used to manage pleural and pericardial effusions. 
For pleural and pericardial effusions consider a dose delay and/or dose reduction.  
Management guidelines for pleural effusions are provided in Table 14. Management guidelines for 
pericardial effusions are provided in Table 15. 
 
 
 
 

 
 
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Table 14. 
 
Management Guidelines for Pleural Effusions  
Event 
Management 
Pleural effusion, 
Grade 1 
• No specific therapy required 
• Close monitoring of cardiac and lung function and imaging 
• Consider diuretics  
Pleural Effusion, 
Grade 2 
• Hold MGC018 
• Consider diuretics or therapeutic thoracentesis 
• Consider corticosteroids: 1 to 2 mg/kg or oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated 
• Resume MGC018 with a one level dose reduction at next scheduled dose 
if pleural effusion resolves to ≤ grade 1 within 21 days. If pleural effusion 
grade 2 recurs further reduce dose by one dose level. 
Pleural Effusion,  
Grade 3 
• Hold MGC 018 
• Therapeutic thoracentesis 
• Consider corticosteroids: 1 to 2 mg/kg or oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated. 
• Resume MGC018 with a one level dose reduction at next scheduled dose 
if pleural effusion resolves to ≤ grade 1 within 21 days. If pleural effusion 
grade 3 recurs further reduce dose by one dose level. 
Pleural Effusion, 
Grade 4 
• Permanently discontinue MGC018 
• Recommend hospitalization with pulmonary consultation and diagnostic 
evaluation including chest X-ray and CT scan. 
• Initiate maximal supportive care including IV corticosteroids. Continue IV 
methylprednisolone 2 mg/kg/day for 5 days then switch to oral 
prednisolone 1 mg/kg/day x 3 days, then reduce to 60 mg/day 
prednisolone. Reduce prednisolone dose by 10 mg every 5-7 days (as 
toxicity allows) until dose is 10 mg/day. Once steroid dose is 10 mg/day, 
reduce by 5 mg every 5-7 days then stop. High doses may be used in 
consultation with the sponsor’s medical monitor. 
 
 
 

 
 
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Table 15. 
 
Management Guidelines for Pericardial Effusions 
 
  
Event 
Management 
Pericardial Effusion, 
Grade 1 
• No specific therapy required 
• Continue MGC018  
Pericardial Effusion, 
Grade 2 
• Hold MGC018 
• Consider diuretics 
• Consider corticosteroids: 1 to 2 mg/kg of oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated 
• Resume MGC018 at next scheduled dose with a one level dose reduction 
if pericardial effusion resolves to ≤ grade 1 within 21 days. If pericardial 
effusion grade 2 recurs further dose reduce by one level. 
Pericardial Effusion, 
Grade 3 
• Hold MGC018 
• Consider pericardiocentesis. 
• Consider corticosteroids: 1 to 2 mg/kg of oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated. 
• Resume MGC018 at next scheduled dose with a one level dose reduction 
if pericardial effusion resolves to ≤ grade 1 within 21 days. If pericardial 
effusion grade 3 recurs further reduce dose by one dose level. 
Pericardial Effusion, 
Grade 4 
• Permanently discontinue MGC018 
• Hospitalize, consider pericardiocentesis 
• Recommend cardiology consult/diagnostic evaluation including 
echocardiogram 
• Initiate maximal supportive care including IV corticosteroids. Continue IV 
methylprednisolone 2 mg/kg/day for 5 days then switch to oral 
prednisolone 1 mg/kg/day x 3 days, then reduce to 60 mg/day 
prednisolone. Reduce prednisolone dose by 10 mg every 5-7 days (as 
toxicity allows) until dose is 10 mg/day. Once steroid dose is 10 mg/day, 
reduce by 5 mg every 5-7 days then stop. High doses may be used in 
consultation with the sponsor’s medical monitor. 
 
 
 

 
 
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NERVOUS SYSTEM EVENTS 
Management guidelines for patients experiencing nervous system toxicity are provided in Table 16. 
Table 16. 
 
Management Guidelines for Nervous System Events 
 
CARDIOVASCULAR EVENTS 
Management guidelines for patients experiencing cardiovascular toxicity are provided in Table 17. 
 
 
Event 
Management 
Grade 1 
• No specific therapy required, close monitoring of neuropathy 
Grade 2  
• Hold MGC018 
• Consider neurology consultation 
• Consider corticosteroids: 1 to 2 mg/kg of oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated. 
• Resume MGC018 at next scheduled dose if symptoms resolve to ≤ grade 1 
within 21 days with or without treatment. 
Grade 3 or 4 
• Permanently discontinue MGC018  
• Consider hospitalization and neurology consultation 
• Begin corticosteroids 2 to 4 mg/kg of oral or IV methylprednisolone or 
equivalent per day divided twice daily. Continue IV methylprednisolone 2 
mg/kg/day for a total of 5 days then switch to oral prednisolone 1 mg/kg/day 
x 3 days, then reduce to 60 mg/day prednisolone. Reduce prednisolone 
dose by 10 mg every 7 days (as toxicity allows) until dose is 10 mg/day. 
Once steroid dose is 10 mg/day, reduce by 5 mg every 5-7 days then stop 

 
 
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Table 17. Management Guidelines for Cardiovascular System Events 
Event 
Management 
Grade 1 
• No specific therapy required; close monitoring 
Grade 2  
• Permanently discontinue MGC018 for patients who experience grade 2 
myocarditis 
• Consider cardiology consultation. Evaluate cardiac biomarkers e.g. creatine 
kinase, troponin, and beta-natriuretic peptide. Echocardiogram and CT 
imaging if clinically indicated. 
• Consider corticosteroids: 1 to 2 mg/kg of oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated. 
Grade 3 or 4 
• Permanently discontinue MGC018  
• Consider hospitalization and cardiology consultation 
• Condier obtaining cardiac biomarkers e.g. creatine kinase, troponin, and 
beta-natriuretic peptide. Echocardiogram and CT imaging if clinically 
indicated. 
• Begin corticosteroids 2 to 4 mg/kg of oral or IV methylprednisolone or 
equivalent per day divided twice daily. Continue IV methylprednisolone 2 
mg/kg/day for a total of 5 days then switch to oral prednisolone 1 mg/kg/day 
x 3 days, then reduce to 60 mg/day prednisolone. Reduce prednisolone 
dose by 10 mg every 5-7 days (as toxicity allows) until dose is 10 mg/day. 
Once steroid dose is 10 mg/day, reduce by 5 mg every 5-7 days then stop. 
• Consider infliximab 
 
MUSCULOSKELETAL TOXICITY 
Management guidelines for patients experiencing musculoskeletal toxicity are provided in Table 18. 
Table 18. 
 
Management Guidelines for Musculoskeletal Events 
Event 
Management 
Grade 1 
• No specific therapy required, close monitoring 
• Consider anti-inflammatory medication e.g. ibuprofen 
Grade 2  
• 
Hold MGC018 
• 
Consider rheumatology consultation 
• 
Consider corticosteroids: 1 to 2 mg/kg of oral prednisone or equivalent per 
day divided twice daily. Taper corticosteroids over 4 weeks or as clinically 
indicated. 

 
 
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INFUSION-RELATED REACTIONS 
Premedications at least 30 minutes prior to each infusion of MGC018 include: acetaminophen 650 to 
1000 mg PO or ibuprofen 400 mg PO, diphenhydramine 50 mg PO or IV or equivalent H1 antagonist, 
famotidine 40 mg PO or 20 mg IV or equivalent H2 antagonist, corticosteroid (e.g dexamethasone 4 mg 
IV or equivalent). 
For subsequent administration of MGC018, participants who had infusion reactions that were not 
adequately or only moderately controlled, other medications may also be considered as part of the pre-
medication regimen for subsequent doses. 
Guidelines for medical management of IRRs during Cycle 1 are provided in Table 19. For subsequent 
cycles, IRRs should be managed according to institutional guidelines. 
 
Table 19. Management Guidelines for Infusion-Related Reactions 
• 
Resume MGC018 at next scheduled dose if symptoms resolve to ≤ grade 
1 within 21 days with or without treatment. 
• 
No dose reduction required after first occurrence 
• 
On resuming MGC018, reduce dose by one dose level after second and 
third occurrences 
• 
Discontinue MGC018 after fourth occurrence 
Grade 3 
• 
Hold or permanently discontinue MGC018  
• 
Consider hospitalization and rheumatology consultation 
• 
Begin corticosteroids 2 to 4 mg/kg of oral or IV methylprednisolone or 
equivalent per day divided twice daily. Continue IV methylprednisolone 2 
mg/kg/day for a total of 5 days then switch to oral prednisolone 1 
mg/kg/day x 3 days, then reduce to 60 mg/day prednisolone. Reduce 
prednisolone dose by 10 mg every 5-7 days (as toxicity allows) until dose 
is 10 mg/day. Once steroid dose is 10 mg/day, reduce by 5 mg every 5-7 
days then stop. 
• 
Consider infliximab 
• 
If not responding within 14 days, consider use of disease modifying 
antirheumatic drugs e.g. sulfazine, methotrexate. 
• 
On resuming MGC018, reduce dose by one dose level after first and 
second occurrences 
• 
Discontinue MGC018 after third occurrence 
Grade 4 
• 
Treat as grade 3 
• 
On resuming MGC018 reduce dose by two dose levels after first 
occurrence 
• 
Discontinue MGC018 after second occurrence 

 
 
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Event 
Management 
IRR, Grade 1  
• Reduce infusion rate to half the rate being given at the time of event onset. 
• Monitor the participant for worsening of condition 
• After the event has resolved, the sponsor-investigator should wait for 
30 minutes while delivering the infusion at the reduced rate. 
• If the infusion is tolerated at the reduced rate for 30 minutes after 
symptoms have resolved, the infusion rate may be increased to the original 
rate. 
• Prophylactic premedication with antipyretics, antihistamines, and/or 
analgesics should be given prior to all subsequent infusions 
IRR, Grade 2 
• Interrupt infusion. 
• Administer aggressive symptomatic treatment (e.g., oral or IV 
antihistamine, anti-pyretic medication, glucocorticoids, epinephrine, 
bronchodilators, oxygen, IV fluids). 
• After symptoms have resolved to baseline or deceased to grade 1, resume 
infusion at half the rate being given at the time of event onset. 
• If the infusion is tolerated at reduced rate for 30 minutes, rate may be 
escalated to original rate after 30 minutes as tolerated 
• For subsequent infusions, prophylactic administration of premedication with 
antihistamines, anti-pyretics, and/or analgesics and monitor closely for 
IRRs. Corticosteroids may also be added (dexamethasone 10 mg IV or 
hydrocortisone 25 to 100 mg IV or higher) 
IRR, Grade 3 or 4 
• Stop infusion. Do not flush tubing. 
• Administer aggressive symptomatic treatment (e.g., oral or IV 
antihistamine, anti-pyretic medication, glucocorticoids, epinephrine, 
bronchodilators, oxygen, IV fluids). 
• If grade 3 infusion reaction occurs, discontinue treatment for that day. If 
symptoms have resolved to baseline within 12 hours, MGC018 may be 
infused the next day with premedication and for any subsequent doses with 
antipyretics, antihistamines, and corticosteroids. 
• Participants who have a grade 3 infusion reaction that does not resolve 
within 12 hours should not receive further treatment with MGC018. 
• Participants who experience a second grade 3 infusion reaction at time of 
rechallenge with MGC018 will permanently discontinue treatment with 
study drugs. 
• Participants who have a grade 4 infusion reaction will not receive further 
treatment with MGC018 
• Reports as an IRE within 24 hours and event as SAE 
IRR = infusion-related reaction, IRE=infusion related event, SAE=serious adverse event 
 

 
 
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4.2.4 
IMP handling and accountability 
All IMPs required for completion of this study will be provided by Macrogenics. The study site (i.e., 
investigator or other authorized personnel [e.g., pharmacist]) is responsible for maintaining records of 
IMP delivery to the site, IMP inventory at the site, IMP use by each patient, and disposition or return of 
unused IMP, thus enabling reconciliation of all IMP received, and for ensuring that patients are provided 
with doses specified by the protocol. 
The study site should follow all instructions included with each shipment of IMP. The study site will 
acknowledge receipt of IMPs supplied by Macrogenics, using the IxRS to confirm the shipment 
condition and content. Any damaged shipments will be replaced. The investigator or designee must 
confirm that appropriate temperature conditions have been maintained during transit for all IMPs 
received and that any discrepancies have been reported and resolved before use of the IMPs. All IMPs 
must be stored in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions, with access limited to the investigator and authorized 
staff. 
Only patients enrolled in the study may receive IMPs, and only authorized staff may supply or 
administer IMPs. 
IMPs will either be disposed of at the study site according to the study site's institutional standard 
operating procedure or be returned to Macrogenics with the appropriate documentation. The site's 
method of destroying Macrogenics-supplied IMPs must be agreed to by Macrogenics. The site must 
obtain written authorization from Macrogenics before any Macrogenics-supplied IMP is destroyed, and 
IMP destruction must be documented on the appropriate form. 
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of by the study site 
should be recorded on the drug accountability log. 
Refer to the pharmacy manual and the MGC018 IB for information on IMP handling, including 
preparation and storage, and accountability. 
 
4.3 
CONCOMITANT THERAPY 
Concomitant therapy consists of any medication (e.g., prescription drugs, over-the-counter drugs, 
vaccines, herbal or homeopathic remedies, nutritional supplements) used by a patient in addition to 
protocol-mandated treatment from 7 days prior to initiation of study treatment to the treatment 
discontinuation visit. All such medications should be reported to the investigator and recorded in the 
patient’s medical records as well as on the Concomitant Medications eCRF.  
 
4.3.1 
Prohibited therapy 
Use of the following concomitant therapies is prohibited as described below: 
• 
Concomitant therapy intended for the treatment of cancer (including, but not limited to, 
chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and herbal therapy), whether 
health authority−approved or experimental, is prohibited during study treatment, until disease 
progression is documented and the patient has discontinued study treatment. 
• 
Live, attenuated vaccines (e.g., FluMist) are prohibited within 4 weeks prior to initiation of study 
treatment, during study treatment, and for 5 months after the last dose of study treatment. 

 
 
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o Available vaccines for COVID-19 will be permitted at any time while a patient is enrolled 
on study but preferably not administered on same day as study drug infusion to avoid 
potential for overlapping immune-related reactions. 
 
4.4 
STUDY ASSESSMENTS 
The schedule of activities to be performed during the study is provided in Appendix 1. All activities must 
be performed and documented for each patient. Patients will be closely monitored for safety and 
tolerability throughout the study. Patients should be assessed for toxicity prior to each dose; dosing will 
occur only if the clinical assessment and local laboratory test values are acceptable. 
All treatment visits must occur ±3 days from the scheduled date unless otherwise noted (see Appendix 
1). All assessments should be performed on the day of the specified visit unless a time window is 
specified. Patients must be assessed for toxicity prior to each dose; dosing will occur only if the clinical 
assessment and local laboratory test values are acceptable. Assessments scheduled on the day of 
study treatment administration should be performed prior to dosing, unless otherwise specified. 
Laboratory tests performed within 14 days of Day 1 of Cycle 1 and within 3 days of Day 1 of 
subsequent cycles do not need to be repeated prior to therapy administration.  
If a holiday, weekend, or other event precludes scheduled dosing, dosing may be postponed to the 
soonest following date, with subsequent dosing continuing on a 28-day schedule. If treatment is 
postponed for fewer than 3 days, the patient can resume the original schedule. 
 
4.4.1 
Informed consent forms (ICFs) 
Written informed consent for participation in the study must be obtained before performing any study-
related procedures. ICFs for enrolled patients and for patients who are not subsequently enrolled will be 
maintained at the study site. 
 
4.4.2 
Medical history, concomitant medication, and demographic data 
Medical history, including clinically significant diseases, surgeries, cancer history (including prior cancer 
therapies and procedures), reproductive status, smoking history, and use of alcohol and drugs of 
abuse, will be recorded at baseline. In addition, all medications (e.g., prescription drugs, over-the-
counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by the patient 
within 7 days prior to initiation of study treatment will be recorded. At the time of each follow-up physical 
examination, an interval medical history should be obtained and any changes in medications and 
allergies should be recorded. Demographic data will include age, sex, and self−reported race/ethnicity. 
 
4.4.3 
ECOG performance status 
Performance status will be measured using the ECOG Performance Status scale at the timepoints 
specified in the schedule of activities in Appendix 1. 
 
4.4.4 
Physical examinations 
A physical examination performed at screening, should include an evaluation of the dermatologic, 
cardiovascular, respiratory, and neurologic systems. Other systems should be examined as clinically 
indicated. Any abnormality identified at baseline should be recorded in the patient’s medical records. 

 
 
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Limited, symptom-directed physical examinations should be performed as clinically indicated during 
subsequent visits. Changes from baseline abnormalities should be recorded in patient notes. New or 
worsened clinically significant abnormalities should be recorded as adverse events on the Adverse 
Event eCRF.  
 
4.4.5 
Tumor response evaluations 
Any evaluable or measurable disease must be documented at screening and re-assessed at each 
subsequent tumor evaluation. Tumor assessments performed as standard of care prior to obtaining 
informed consent and within 28 days prior to initiation of study treatment do not have to be repeated at 
screening. Measurable disease is a requirement for study inclusion and response will be assessed by 
the investigator per RECIST v1.1 at baseline. Patients will undergo tumor assessments every 2 cycles 
while on study until radiographic disease progression per RECIST v1.1 or loss of clinical benefit as 
determined by the investigator. Tumor assessments should be performed during the last week of the 
cycle and before the start of treatment in the next cycle (see Appendix 1). At the investigator’s 
discretion, tumor assessments may be repeated at any time if progressive disease is suspected. 
Screening assessments must include CT or magnetic resonance imaging (MRI) scans (with IV contrast 
unless contraindicated) of the chest, abdomen, and pelvis. If a positron emission tomography (PET)/CT 
scan is performed, the CT portion of the study must be consistent with the standards of a full-contrast 
diagnostic CT scan unless IV contrast is contraindicated. A CT scan with contrast or MRI scan of the 
head must be done at screening to evaluate for the presence of CNS metastases in all patients (MRI 
preferred). An MRI scan of the head is required to confirm or refute the diagnosis of CNS metastases at 
baseline in the event of an equivocal CT scan. At the investigator's discretion, other methods 
of assessment of measurable disease as per RECIST v1.1 may be used. 
All measurable and evaluable lesions identified at baseline should be re-assessed at each subsequent 
tumor evaluation. The same radiographic procedures used to assess disease sites at screening should 
be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans). Stable 
brain metastases must be evaluated with each subsequent tumor assessment with the same 
radiographic procedure as the baseline study. Patients without brain metastases do not need brain 
scans for subsequent on-treatment tumor assessment unless clinically warranted or part of standard-of-
care treatment. 
 
4.4.6 
Laboratory, biomarker, and other biological samples 
Samples for the following laboratory tests must be reviewed prior to dosing. See Appendix 1 for 
specifics related to which lab tests are required at specific time points during study (“screening” vs “on 
treatment”, etc.): 
• 
Hematology: WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count 
(neutrophils, eosinophils, basophils, monocytes, lymphocytes, other cells). 
• 
Chemistry panel (serum or plasma): bicarbonate or total carbon dioxide (if considered standard of 
care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, 
albumin, phosphorus, calcium, total bilirubin, alkaline phosphatase, ALT, and AST. 
• 
Coagulation: INR, and aPTT (screening only). 
• 
Thyroid function testing: thyroid-stimulating hormone (TSH), free triiodothyronine (T3) (or total T3 
for sites where free T3 is not performed), and free thyroxine (also known as T4) at screening only. 
Repeat thyroid function testing as clinically indicated.  

 
 
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• 
Pregnancy test 
All women of childbearing potential will have a serum pregnancy test at screening, and during 
the study, urine pregnancy tests will be performed at every cycle and after study treatment is 
discontinued. If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy 
test. 
A woman is considered to be of childbearing potential if she is postmenarchal, has not 
reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified 
cause other than menopause), and has not undergone surgical sterilization (removal of 
ovaries and/or uterus). 
 
The following samples will be sent to the PI or a designee for analysis or banked for subsequent 
analysis: 
• 
Peripheral blood to be obtained on day 1 of cycle 1, day 1 of cycle 3, and at progression 
• 
Prior to treatment initiation, tumor tissue will be obtained following progression on most-recent 
therapy for determination of biomarker status including exploratory correlative analyses. Please 
refer to the lab manual for details. If a biopsy is not feasible and/or safe, it may be waived after 
discussion with the principal investigator. In this case, we will obtain archival tissue if available.  
 
For sampling procedures, storage conditions, and shipment instructions, see the laboratory manual.  
Should a patient withdraw from the study, samples collected prior to the date of withdrawal may still be 
analyzed, unless the patient specifically requests that the samples be destroyed or local laws require 
destruction of the samples. However, if samples have been tested prior to withdrawal, results from 
those tests will remain as part of the overall research data. 
Personnel performing laboratory analysis or biostatistics will only have access to random specimen 
codes and/or study subject ID numbers and not specific identifiers. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data derived from 
these analyses will generally not be provided to patients unless required by law and may be disclosed 
to third parties only as permitted by the ICF (or separate authorization for use and disclosure of 
personal health information) signed by the patient. The aggregate results of any conducted research 
will be available in accordance with the effective investigator policy on study data publication. 
 
4.5 
TREATMENT, PATIENT, AND STUDY DISCONTINUATION 
4.5.1 
Treatment discontinuation 
Patients must permanently discontinue study treatment if they experience any of the following: 
• 
Intolerable toxicity related to study treatment, determined by the investigator to be unacceptable 
given the individual patient’s potential response to therapy and severity of the event 
• 
Any medical condition that may jeopardize the patient’s safety if he or she continues study 
treatment 
• 
Investigator determines it is in the best interest of the patient 
• 
Use of another non-protocol anti-cancer therapy 
• 
Pregnancy 

 
 
48 
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• 
Loss of clinical benefit as determined by the investigator after an integrated assessment of 
radiographic and biochemical data, local biopsy results (if available), and clinical status (e.g., 
symptomatic deterioration such as pain secondary to disease)   
• 
Radiographic disease progression per RECIST v1.1 or symptomatic deterioration attributed to 
disease progression 
In select scenarios, patients may continue therapy in setting of radiographic progression and ongoing 
clinical benefit, as assessed by investigator. In this scenario, medical interventions such as stereotactic 
radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) to isolated sites of disease 
progression in the setting of otherwise ongoing treatment response will be allowed on a case-by-case 
basis with PI approval. 
The primary reason for study treatment discontinuation should be documented in the patient’s medical 
records and on the appropriate eCRF. Patients who have received ≥1 cycle of study therapy and 
discontinue study treatment prematurely will not be replaced. Patients will return to the clinic for a 
treatment discontinuation visit ≤ 30 days after the last dose of study treatment. The visit at which 
response assessment shows progressive disease may be used as the treatment discontinuation visit. 
After the end of treatment visit, all adverse events (including serious adverse events [see Section 
5.2.2], regardless of attribution, will be recorded until 60 days after the last dose of study treatment or 
until initiation of another anti-cancer therapy, whichever occurs first. Protocol-defined events of special 
interest [see Section 5.2.3]) will be recorded until 60 days after the last dose of study treatment 
regardless of whether or not subsequent anti-cancer therapy is initiated. Ongoing adverse events 
thought to be related to study treatment will be followed until the event has resolved to baseline grade, 
the event is assessed by the investigator as stable, new anti-tumor treatment is initiated, the patient is 
lost to follow up, the patient withdraws consent, or it has been determined that the study treatment or 
participation is not the cause of the adverse event. 
Patients who discontinue study treatment for any reason other than progressive disease or loss of 
clinical benefit will continue to undergo tumor response assessments as outlined in the schedule of 
activities (see Appendix 1). 
After treatment discontinuation, information on survival follow-up and new anti-cancer therapy will be 
collected via telephone calls, patient medical records, and/or clinic visits approximately every 6 months 
for 2 years (unless the patient withdraws consent or the PI terminates the study). 
 
4.5.2 
Patient discontinuation from study 
Patients have the right to voluntarily withdraw from the study at any time for any reason. In addition, the 
investigator has the right to withdraw a patient from the study at any time. Reasons for withdrawal from 
the study may include, but are not limited to, the following: 
• 
Withdrawal of consent 
• 
Study termination or site closure 
• 
Patient non-compliance, defined as failure to comply with protocol requirements as determined by 
the Investigator 
Every effort should be made to obtain information on patients who withdraw from the study. The 
primary reason for withdrawal from the study should be documented in the patient’s medical records 
and on the appropriate eCRF. If a patient requests to be withdrawn from the study, this request must be 
documented in the source documents and signed by the investigator. Patients who withdraw from the 
study will not be replaced. Study withdrawal will not prohibit the analysis of clinical data and samples 
collected prior to withdrawal of study consent. 

 
 
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If a patient withdraws from the study, the study staff may use a public information source (e.g., county 
records) to obtain information about survival status. 
 
4.5.3 
Study discontinuation 
The investigator has the right to terminate this study at any time. Reasons for terminating the study may 
include, but are not limited to, the following: 
• 
The incidence or severity of adverse events in this or other studies indicates a potential health 
hazard to patients 
• 
Patient enrollment is unsatisfactory 
 
4.6 
MULTI-INSTITUTIONAL TRIAL MANAGEMENT 
4.6.1 
Personnel 
At each site, personnel dedicated to this protocol will be: 
 
- A study PI 
 
- A research coordinator 
 
- A data manager 
In addition, the Georgetown University Lombardi Comprehensive Cancer Center (LCCC) Consortium 
Investigator Initiated Trial (IIT) Office will play the primary role in coordinating the trial between 
Lombardi-Georgetown and additional sites. The Georgetown University Lombardi Comprehensive 
Cancer Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office will be the main point of 
contact for Dr. Kim (study Principal Investigator) and the other site PIs for any study related concerns, 
and to confirm eligibility of each patient being considered for enrollment (including “remote” 
confirmation of eligibility for the patients being screened at other sites). The Georgetown University 
Lombardi Comprehensive Cancer Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office will 
also be the point of contact for the data managers for data entry questions. Finally, the Georgetown 
LCCC Consortium IIT Office will play a major role in regulatory coordination of the study, specifically by: 
1) reviewing and confirming all study-related adverse events; 2) ensuring that sites are submitting all 
severe adverse event (SAE) reports to the site IRB per local IRB policy; 3) gathering and preparing all 
necessary primary source data for review/audit. 
 
4.6.2 
Patient enrollment 
If a patient is being screened for enrollment, the local research coordinator must send an email within 
24 hours containing the patient’s initials to the local PI, to Dr. Kim, and to the Georgetown University 
Lombardi Comprehensive Cancer Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office. If a 
patient is successfully screened, the local research coordinator must send all supporting source 
documentation used to verify eligibility to the Georgetown University Lombardi Comprehensive Cancer 
Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office (by secure email) for review, to 
 
Patients should not start therapy until Dr. Kim and the LCCC Consortium IIT Office have reviewed the 
patient’s records and confirmed that the patient is indeed eligible for enrollment. Once eligibility is 
confirmed, a unique study ID will be assigned/confirmed by the LCCC Consortium IIT Office. Study IDs 
will denote study site, and patient number enrolled in cohort. For example, if the first patient enrolled is 

 
 
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enrolled at Georgetown University and the second patient enrolled is enrolled at Washington Hospital 
Center the unique IDs for these patients would be GUH-001 and WHC-002, respectively. 
 
4.6.3 
Data collection and management 
Patient data will be entered into the online accessible database. This database is housed at Lombardi-
Georgetown but is accessible anywhere there is internet access. The data manager and research 
coordinator at each site will attend an online training session so that they may learn how to enroll data 
into the database. All screening data should be entered prior to starting therapy, and all ongoing patient 
data should be entered within 10 business days of each patient visit. 
 
4.6.4 
Conference calls 
A bimonthly conference call will be held between Lombardi-Georgetown and the other sites. 
Georgetown University will conduct the bimonthly conference call to review screening and enrollment 
metrics, patient milestone dates, troubleshoot study challenges, and answer site questions. Site PI, 
participating investigators, study coordinators and data managers may attend. At least one site 
representative should attend each call. 
 
4.6.5 
Trial monitoring 
The LCCC Consortium IIT Office will request primary source documents for the patients to be 
monitored. This will include collecting copies of the primary source data for any patients treated at other 
sites and/or reviewing Electronic Health Records when accessible. Trial monitoring may be conducted 
in person or remotely by the LCCC Consortium IIT Office.  
 
5. 
ASSESSMENT OF SAFETY 
5.1 
SAFETY PLAN 
The safety plan for patients in this study is based on clinical experience with MGC018 in completed and 
ongoing studies.  
Measures will be taken to ensure the safety of patients participating in this study, including the use of 
stringent inclusion and exclusion criteria and close monitoring of patients during the study. 
Administration of all study therapies will be performed in a monitored setting in which there is 
immediate access to trained personnel and adequate equipment and medicine to manage potentially 
serious reactions. Guidelines for managing patients who experience anticipated adverse events, 
including criteria for treatment interruption or discontinuation, are provided in Section 4.2.3.  
Refer to Sections 5.2−5.6 for details on safety reporting (e.g., adverse events, pregnancies) for this 
study. 
 
5.1.1 
Risks associated with MGC018 
MGC 018 has been associated with risks such as the following: infusion-related reactions, pneumonitis, 
myelosuppression, peripheral edema, severe cutaneous adverse reactions, pericardial effusion, pleural 
effusion, ocular toxicity, arthritis, and colitis. Please refer to the MGC018 IB for a detailed description of 
anticipated safety risks for MGC018. 

 
 
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5.2 
SAFETY PARAMETERS AND DEFINITIONS 
Safety assessments will consist of monitoring and reporting adverse events including serious adverse 
events and adverse events of special interest, performing protocol-specified safety laboratory 
assessments, measuring protocol-specified vital signs, and conducting other protocol-specified tests 
that are deemed critical to the safety evaluation of the study. 
 
5.2.1 
Adverse events (AEs) 
According to the ICH guideline for Good Clinical Practice (GCP), an AE is any untoward medical 
occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of 
causal attribution. An AE can be an unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an IMP or other protocol-imposed 
intervention, regardless of attribution. This includes the following: 
• 
AEs not previously observed in the subject that emerge during the protocol-specified AE reporting 
period, including signs or symptoms associated with SCLC that were not present prior to the AE 
reporting period. 
• 
Complications that occur as a result of protocol-mandated interventions (e.g., invasive procedures 
such as tumor biopsy). 
• 
Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is associated 
with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation 
from study treatment. 
• 
If applicable, AEs that occur prior to assignment of study treatment associated with medication 
washout, no treatment run-in, or other protocol-mandated intervention. 
• 
Preexisting medical conditions (other than the condition being studied) judged by the investigator 
to have worsened in severity or frequency or changed in character during the protocol-specified AE 
reporting period.  
 
5.2.2 
Serious adverse events (SAEs) 
An AE should be classified as an SAE if any of the following criteria are met: 
• 
It results in death (i.e., the AE actually causes or leads to death). 
• 
It is life threatening (i.e., the AE, in the view of the investigator, places the subject at immediate risk 
of death. It does not include an AE that, had it occurred in a more severe form, might have caused 
death.). 
• 
It requires hospitalization ≥ 24 hours or prolongs inpatient hospitalization. 
• 
It results in persistent or significant disability/incapacity (i.e., the AE results in substantial disruption 
of the subject’s ability to conduct normal life functions). 
• 
It results in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the 
IMP. 
• 
It is considered a significant medical event by the investigator based on medical judgment (e.g., 
may jeopardize the subject or may require medical/surgical intervention to prevent one of the 
outcomes listed above). 

 
 
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The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse 
event (e.g., rated as mild, moderate, or severe, or according to NCI CTCAE); the event itself may be of 
relatively minor medical significance (such as severe headache without any further findings). Severity 
and seriousness need to be independently assessed for each adverse event recorded on the eCRF. 
SAEs are required to be reported by the investigator to the sponsor immediately (i.e., no more than 24 
hours after learning of the event; see Section 5.4. and 5.5 for reporting instructions). 
 
5.2.3 
Adverse events of special interest (AESIs) 
AESIs are a subset of events to monitor of scientific and medical concern specific to the product, for 
which ongoing monitoring and rapid communication by the Investigator to the study sponsor is required 
(no more than 24 hours after learning of the event). Such an event might require further investigation in 
order to characterize and understand it. Depending on the nature of the event, rapid communication by 
the trial sponsor to other parties (e.g., Regulatory Authorities; Macrogenics) may also be warranted. 
AESIs for this study include the following: 
• 
Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination 
with either an elevated bilirubin or clinical jaundice, as defined by Hy’s law: 
Treatment-emergent ALT or AST > 3 × ULN in combination with total bilirubin > 2 × ULN 
Treatment-emergent ALT or AST > 3 × ULN in combination with clinical jaundice 
• 
Grade 3 or higher pneumonitis 
• 
Grade 3 or higher pleural and/or pericardial effusion 
• 
Grade 3 or higher ocular toxicities (e.g., uveitis, retinitis, optic neuritis) 
• 
Severe cutaneous reactions (e.g., Stevens-Johnson syndrome, dermatitis bullous, toxic epidermal 
necrolysis) 
 
5.3 
METHODS AND TIMING FOR ASSESSING AND RECORDING SAFETY 
VARIABLES 
The investigator is responsible for ensuring that all AEs and SAEs that are observed or reported during 
the study are recorded on the AE eCRF and reported to the FDA, appropriate IRB, and Macrogenics 
Inc. in accordance with Code of Federal Regulations (CFR) 312.32 (IND Safety Reports).  
For each adverse event recorded on the AE eCRF, the investigator will assess seriousness (see 5.2.2), 
severity (see 5.3.1.3) and causality (5.3.1). 
All communication regarding AEs, SAEs, AESIs and/or protocol deviations from sub-site investigators 
and co-investigators should be directed to Chul Kim, MD (Study PI) at 
 
 
5.3.1 
Assessment of adverse event 
All AEs and SAEs whether volunteered by the patient, discovered by study personnel during 
questioning, or detected through physical examination, laboratory test, or other means will be reported 
appropriately. Each reported AE or SAE will be described by its duration (i.e., start and end dates), 
regulatory seriousness criteria if applicable, suspected relationship to study therapies (see following 
guidance), and actions taken. 

 
 
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To ensure consistency of AE and SAE causality assessments, investigators should apply the following 
general guideline: 
Yes 
There is a plausible temporal relationship between the onset of the AE and administration of study 
drug, and the AE cannot be readily explained by the subject’s clinical state, intercurrent illness, or 
concomitant therapies; and/or the AE follows a known pattern of response MGC018; and/or the AE 
abates or resolves upon discontinuation of study drug and, if applicable, reappears upon re-challenge. 
No 
Evidence exists that the AE has an etiology other than study drug (e.g., preexisting medical condition, 
underlying disease, intercurrent illness, or concomitant medication); and/or the AE has no plausible 
temporal relationship to study drug administration. 
Expected adverse events are those adverse events that are listed or characterized in the current 
MGC018 IB. 
Unexpected adverse events are those not listed in the current IB or not identified. This includes adverse 
events for which the specificity or severity is not consistent with the description in the IB. 
 
5.3.1.1 
Diagnosis vs. signs and symptoms 
If known at the time of reporting, a diagnosis should be reported rather than individual signs and 
symptoms (e.g., record only liver failure or hepatitis rather than jaundice, asterixis, and elevated 
transaminases). However, if a constellation of signs and/or symptoms cannot be medically 
characterized as a single diagnosis or syndrome at the time of reporting, it is acceptable to report the 
information that is currently available. If a diagnosis is subsequently established, it should be reported 
as follow-up information. 
 
5.3.1.2 
Deaths 
All deaths that occur during the protocol-specified AE reporting period (see Section 5.3.2), that are 
attributed by the investigator solely to progression of SCLC should be recorded on the Death Attributed 
to Progressive Disease eCRF. All other deaths that occur during the adverse event reporting period, 
regardless of relationship to study treatment, must be recorded on the AE eCRF and immediately 
reported to the study sponsor. When recording a death, the event or condition that caused or 
contributed to the fatal outcome should be reported as the single medical concept. If the cause of death 
is unknown and cannot be ascertained at the time of reporting, report “Unexplained Death”. The DSMC 
will monitor the frequency of deaths from all causes. 
 
5.3.1.3 
Preexisting medical conditions 
A preexisting medical condition is one that is present at the start of the study. Such conditions should be 
reported as medical and surgical history. A preexisting medical condition should be re-assessed 
throughout the trial and reported as an AE or SAE only if the frequency, severity, or character of the 
condition worsens during the study. When reporting such events, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors (e.g., “more frequent 
headaches”). 
 

 
 
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5.3.1.4 
Hospitalizations for medical or surgical procedures 
Any AE that results in hospitalization or prolonged hospitalization should be documented and reported 
as an SAE. If a subject is hospitalized to undergo a medical or surgical procedure as a result of an AE, 
the event responsible for the procedure, not the procedure itself, should be reported as the SAE. For 
example, if a subject is hospitalized to undergo coronary bypass surgery, record the heart condition that 
necessitated the bypass as the SAE. 
Hospitalizations for the following reasons do not require reporting as an AE or SAE: 
• 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for 
preexisting conditions 
• 
Hospitalization or prolonged hospitalization required to allow efficacy measurement for the study 
• 
Hospitalization or prolonged hospitalization for scheduled therapy of the target disease of the study 
• 
Hospitalization solely due to progression of the underlying cancer 
• 
Hospitalization for respite care 
• 
Hospitalization for a pre-existing condition, provided that all of the following are met: 
The hospitalization was planned prior to the study or was scheduled during the study when 
elective surgery became necessary because of the expected normal progression of the 
disease. 
The patient has not experienced an adverse event 
An event that leads to hospitalization under the following circumstances is not considered to be a SAE, 
but should be reported as an adverse event instead: 
• 
Hospitalization that was necessary because of patient requirement for outpatient care outside of 
normal outpatient clinic operating hours 
 
5.3.1.5 
Assessment of severity of AEs 
The adverse event severity grading scale for the NCI CTCAE v 5.0 will be used for assessing adverse 
event severity. Table 21 should be used for assessing severity for adverse events that are not 
specifically listed in the NCI CTCAE. 
 
Table 20. 
 
Adverse Event Severity Grading Scale for Events Not Specifically Listed 
in NCI CTCAE 
• 
Grade 
• 
Severity 
• 
1 
• 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; or intervention not indicated 
• 
2 
• 
Moderate; minimal, local, or non-invasive intervention indicated; or 
limiting age−appropriate instrumental activities of daily living a 
• 
3 
• 
Severe or medically significant, but not immediately 
life−threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; or limiting self-care activities of daily living b,c 
• 
4 
• 
Life-threatening consequences or urgent intervention indicated d 

 
 
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• 
5 
• 
Death related to adverse event d 
NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events. 
Note: Based on the most recent version of NCI CTCAE (v5.0), which can be found at: 
http://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm 
a Instrumental activities of daily living refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc.  
b Examples of self-care activities of daily living include bathing, dressing and undressing, 
feeding oneself, using the toilet, and taking medications, as performed by patients who are 
not bedridden. 
c If an event is assessed as a "significant medical event," it must be reported as a SAE  
d Grade 4 and 5 events must be reported as SAEs  
 
5.3.1.6 
Pregnancies 
5.3.1.6.1 
Pregnancies in female patients 
Female patients of childbearing potential will be instructed to immediately inform the investigator if they 
become pregnant during the study or within 6 months after the final dose of study treatment. Pregnancy 
should not be recorded on the Adverse Event eCRF. The investigator should discontinue study 
treatment and counsel the patient, discussing the risks of the pregnancy and the possible effects on the 
fetus. Monitoring of the patient should continue until conclusion of the pregnancy. Any SAEs associated 
with the pregnancy (e.g., an event in the fetus, an event in the mother during or after the pregnancy, or 
a congenital anomaly/birth defect in the child) should be reported on the Adverse Event eCRF. 
Abortion, whether accidental, therapeutic, or spontaneous, should always be classified as serious, and 
expeditiously reported to the sponsor as an SAE. Similarly, any congenital anomaly/birth defect in a 
child born to a female subject exposed to study treatment should be reported to the study sponsor as 
an SAE. 
 
5.3.1.6.2 
Pregnancies in female partners of male patients 
Male patients will be instructed through the ICF to immediately inform the investigator if their partner 
becomes pregnant during the study treatment, or within 90 days after the final dose of MGC018. 
Attempts should be made to collect and report details of the course and outcome of any pregnancy in 
the partner of a male patient exposed to study treatment. When permitted by the site, the pregnant 
partner would need to sign an Authorization for Use and Disclosure of Pregnancy Health Information to 
allow for follow-up on her pregnancy. An investigator who is contacted by the male patient or his 
pregnant partner may provide information on the risks of the pregnancy and the possible effects on the 
fetus, to support an informed decision in cooperation with the treating physician and/or obstetrician. 
 
5.3.1.7 
Other special Situations reports 
The following other Special Situations Reports should be collected even in the absence of an Adverse 
Event and transmitted to Macrogenics: 
• 
Data related to the Product usage during breastfeeding 
• 
Data related to overdose, abuse, misuse or medication error (including potentially exposed or 
intercepted medication errors) 

 
 
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• 
In addition, reasonable attempts should be made to obtain and submit the age or age group of 
the patient, in order to be able to identify potential safety signals specific to a particular 
population 
 
5.3.1.8 
Product complaints 
A product complaint is defined as any written or oral information received from a complainant that 
alleges deficiencies related to identity, quality, safety, strength, purity, reliability, durability, 
effectiveness, or performance of a product after it has been released and distributed to the commercial 
market or clinical trial. 
 
5.3.2 
Adverse event reporting period 
Investigators will seek information on adverse events at each patient contact. All adverse events, 
whether reported by the patient or noted by study personnel, will be recorded in the patient's medical 
record. 
After informed consent has been obtained but prior to initiation of study treatment, only SAEs caused 
by a protocol-mandated intervention (e.g., invasive procedures such as biopsies, discontinuation of 
medications) should be reported. 
After initiation of study treatment, all AEs will be reported until 30 days after the final dose of study 
treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and SAEs will 
continue to be reported until 60 days after the final dose of study treatment or until initiation of new 
systemic anti-cancer therapy, whichever occurs first. AESIs will continue to be reported until 60 days 
after the final dose of study treatment, regardless of initiation of new anti-cancer therapy. 
Investigators should record all case details that can be gathered immediately (i.e., within 24 hours after 
learning of the event) on the AE eCRF and sent to Macrogenics contact specified above in section 5.4. 
All SAE and AESIs should be sent within 1 business day of date of SAE/AESI identification. 
 
5.3.2.1 
Post-study adverse events 
After the end of the adverse event reporting period (defined as 30 days after last dose of study drug for 
all adverse events and 60 days for adverse events of special interest), the investigator should report all 
deaths (regardless of cause), and any SAE including development of cancer or a congenital anomaly in 
a subsequently conceived offspring of a female subject who participated in the study (including 
pregnancy occurring in the partner of a male study subject) that is believed to be related to prior 
exposure to study drug through a long-term survival follow-up eCRF. 
Case Transmission Verification will be performed by both parties during this period twice per year to 
ensure successful transmission of Single case reports  
 
5.3.3 
MedWatch 3500A reporting guidelines 
Events requiring reporting to the Sponsor-Investigator may be reported using the provided Macrogenics 
forms (SAE Report form, Pregnancy Exposure form) or a Medwatch form. If a MedWatch form 3500A is 
used to report an event, then in addition to completing appropriate patient demographic (Section A) and 

 
 
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suspect medication information (Section C and D), the report should include the following information 
within the Event Description (Section B.5) of the MedWatch 3500A form: 
• 
Protocol number and title description  
• 
Description of event, severity, treatment, and outcome if known 
• 
Supportive laboratory results and diagnostics (Section B.6) 
• 
Investigator’s assessment of the relationship of the adverse event to each investigational product 
and suspect medication 
 
5.3.4 
Follow-up after adverse events 
5.3.4.1 
Investigator follow-up 
The investigator should follow each AE until the event has resolved to baseline grade or better, the 
event is assessed as stable by the investigator, the patient is lost to follow-up, or the patient withdraws 
consent. Every effort should be made to follow all SAEs considered to be related to study treatment or 
trial-related procedures until a final outcome can be reported. 
During the study period, resolution of AEs (with dates) should be documented on the AE eCRF and in 
the patient's medical record to facilitate source data verification. 
All pregnancies reported during the study should be followed until pregnancy outcome. 
 
5.3.4.2 
Sponsor follow-up 
For SAEs, AESIs and pregnancies, the sponsor or a designee may follow up by telephone, fax, email, 
and/or a monitoring visit to obtain additional case details and outcome information (e.g., from hospital 
discharge summaries, consultant reports, autopsy reports) in order to perform an independent medical 
assessment of the reported case. 
 
5.3.4.3 
Follow-up information 
Additional information may be added to a previously submitted report by any of the following methods: 
• 
Adding to the original MedWatch 3500A report and submitting it as follow-up 
• 
Adding supplemental summary information and submitting it as follow-up with the original 
MedWatch 3500A form  
• 
Summarizing new information and faxing it with a cover letter including patient identifiers (i.e., 
D.O.B. initial, patient number), protocol description and number, if assigned, brief adverse event 
description, and notation that additional or follow-up information is being submitted (The patient 
identifiers are important so that the new information is added to the correct initial report) 
MedWatch 3500A (Mandatory Reporting) form is available at: 
https://www.fda.gov/media/69876/download 
 

 
 
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5.3.5 
Reporting to regulatory authorities, ethics committees and investigators 
The investigator, as the sponsor of the study, will be responsible for the expedited reporting of safety 
reports originating from the study to the regulatory authorities (FDA) where it has filed a clinical trial 
approval, in compliance with local regulations.  
The study PI, as the sponsor of the study, will be responsible for the expedited reporting of safety 
reports originating from the study. 
The study PI will be responsible for the expedited reporting of safety reports originating from the study 
to the IRB and DSMC, where applicable.  
The study PI will be responsible for the distribution of safety information to its own investigators, where 
relevant, in accordance with local regulations. 
Additional reporting requirements for IND holders: 
For Investigator-Initiated IND Studies, some additional reporting requirements for the FDA apply in 
accordance with the guidance set forth in 21 CFR § 600.80. 
Events meeting the following criteria need to be submitted to the FDA as expedited IND safety reports 
according to the following guidance and timelines: 
7 calendar day telephone or fax report 
The investigator is required to notify the FDA of any fatal or life-threatening adverse event that is 
unexpected and assessed by the investigator to be possibly related to the use of MGC018. An 
unexpected adverse event is one that is not already described in the MGC018 IBs. Such reports are to 
be telephoned or faxed to the FDA within 7 calendar days of first learning of the event. 
15 calendar day written report 
The investigator is also required to notify the FDA and all participating investigators, in a written IND 
safety report, of any serious, unexpected AE that is considered reasonably or possibly related to the 
use of MGC018. An unexpected adverse event is one that is not already described in the MGC018 IBs. 
Written IND safety reports should include an analysis of similar events in accordance with regulation 21 
CFR § 312.32. All safety reports previously filed by the investigator with the IND concerning similar 
events should be analyzed and the significance of the new report in light of the previous, similar reports 
commented on. 
Written IND safety reports with analysis of similar events are to be submitted to the FDA, Macrogenics, 
and all participating investigators within 15 calendar days of first learning of the event. The FDA prefers 
these reports on a MedWatch 3500 form, but alternative formats are acceptable (e.g., summary letter). 
FDA fax number for IND Safety Reports: 
Fax: 1 (800) FDA 0178 
 
All written IND Safety Reports submitted to the FDA by the investigator must also be sent to 
Macrogenics: 
 

 
 
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And the investigator will be responsible for the distribution of safety information to the site IRB 
per local IRB reporting guidelines: 
 
 
 
5.4 
ADVERSE EVENT REPORTING TO MACROGENICS 
The investigator will be responsible for collecting all protocol-defined AE/SAE data, pregnancy reports 
(including pregnancy occurring in the partner of a male study subject), other special situation reports, 
AESIs, product complaints with an AE where the patient has been exposed to the product. The 
completed MedWatch form should be sent to the Georgetown University Lombardi Comprehensive 
Cancer Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office and Macrogenics contact 
specified below. Transmission of these reports (initial and follow-up) will be either electronically via 
email or by fax and within the timelines specified below: 
Email: 
 
 
Investigators must report all the above mentioned single case reports adequately to the LCCC 
Consortium IIT Office and Macrogenics on a MedWatch or CIOMS I or on Macrogenics 
approved SAE form within one (1) business day of the awareness date 
The investigator will forward quarterly listings of non-serious AEs originating from the study to 
Macrogenics. 
 
5.4.1 
Case transmission verification of single case reports 
The study PI agrees to conduct the case transmission verification to ensure that all single case reports 
have been adequately received by Macrogenics via PI emailing Macrogenics a quarterly line-listing 
documenting single case reports in the preceding time period.  
The periodic line-listing will be exchanged within seven (7) calendar days of the end of the agreed time 
period. Confirmation of receipt should be received within the time period mutually agreed upon.               
If discrepancies are identified, the Study PI as sponsor and Macrogenics will cooperate in resolving the 
discrepancies. The responsible individuals for each party shall handle the matter on a case-by-case basis 
until satisfactory resolution.  The sponsor shall receive reconciliation guidance documents within the 
‘Activation Package’. 
Following case transmission verification, single case reports which have not been received by 
Macrogenics shall be forwarded by the study PI to Macrogenics within five (5) calendar days from request 
by Macrogenics. 
At the end of the study, a final cumulative case transmission verification report will be sent to Macrogenics. 
 
5.5 
AGGREGATE REPORTS 
Development safety update report 

 
 
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As study sponsor, the PI, in conjunction with Georgetown University IRB and DSMC, will be responsible 
for the preparation of their own Development Safety Update Report (DSUR) for the study and for the 
submission of the report to the regulatory authorities and other bodies such as ethics committees, 
where applicable. The study PI agrees to share a copy of their own DSUR with Macrogenics as soon as 
reasonably possible after completion.  
Macrogenics agrees to forward to the study PI an executive summary of the Macrogenics DSUR upon 
request. Furthermore, Macrogenics agrees that the study PI may cross-reference the executive 
summary of the Macrogenics DSUR, as applicable. 
Other reports  
The PI will forward a copy of the Final Study Report to Macrogenics upon completion of the study.  
 
5.6 
STUDY CLOSE-OUT 
Any study report submitted to the FDA by the investigator should be copied to Macrogenics. This 
includes all IND annual reports and the Clinical Study Report (final study report). Additionally, any 
literature articles that are a result of the study should be sent to Macrogenics. Copies of such reports 
should be mailed to the assigned Clinical Operations contact for the study. 
 
 
5.7 
QUERIES 
Queries related to the study will be answered by the PI and Georgetown University. However, 
responses to all safety queries from regulatory authorities or for publications will be discussed and 
coordinated between all parties, including Macrogenics. The study PI agrees that it shall not address 
such queries from regulatory authorities and other sources relating to the study therapy independently 
but shall involve Macrogenics in such queries. 
All parties will use all reasonable effort to ensure that deadlines for responses to urgent requests for 
information or review of data are met. The parties will clearly indicate on the request the reason for 
urgency and the date by which a response is required. 
 
5.8 
SIGNAL & RISK MANAGEMENT 
Macrogenics is responsible for safety signal management (signal detection and/or evaluation) for their own 
products. However, it is agreed that study PI, as sponsor of the study, will be primarily responsible for 
assessment of the benefit-risk balance of the study. 
If study PI issues a safety communication relevant for Macrogenics (i.e., a safety issue that notably impacts 
the benefit-risk balance of the study and / or triggers any changes to the study) this will be sent to 
Macrogenics within five (5) business days of its internal approval. 
As needed, Macrogenics will reasonably assist study PI with signal and risk management activities related 
to the product within the study. Macrogenics will also provide study PI with any new relevant information 
that may modify or supplement known data regarding the Product (e.g., relevant Dear Investigator Letter). 
 

 
 
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5.9 
COMPLIANCE WITH PHARMACOVIGILANCE AGREEMENT/AUDIT 
The parties shall follow their own procedures for adherence to AE reporting timelines. Each party shall 
monitor and, as applicable, request feedback from the other party regarding AE report timeliness in 
accordance with its own procedures. The parties agree to provide written responses in a timely manner 
to inquiries from the other party regarding AE reports received outside the agreed upon agreement 
timelines. If there is any detection of trends of increasing or persistent non-compliance to transmission 
timelines stipulated in this agreement, both parties agree to conduct ad hoc or institute a regular joint 
meeting to address the issue. 
In case of concerns related to non-compliance of processes, other than exchange timelines, with this 
agreement, the parties will jointly discuss and collaborate on clarifying and resolving the issues causing 
non-compliance. Every effort will be made by the non-compliant party to solve the non-compliance 
issues and inform the other party of the corrective and preventative actions taken. 
Upon justified request, given sufficient notice of no less than sixty (60) calendar days, an audit under 
the provisions of this agreement can be requested by either party. The parties will then discuss and 
agree in good faith upon the audit scope, agenda and execution of the audit. The requesting party will 
bear the cost of the audit. 
 
6. 
STATISTICAL CONSIDERATIONS 
6.1 
DETERMINATION OF SAMPLE SIZE 
The primary efficacy endpoint of this study is to evaluate the ORR of the study drug MGC018 in 
patients with ES-SCLC. Simon’s two-stage optimal design is used for sample size calculation. 
We plan to enroll up to 17 patients. The null hypothesis that the true response rate is 5% will be tested 
against a one-sided alternative. This design yields a type I error rate of 4.7% and power of 81.2% when 
the true response rate is 25%. 
 
6.2 
PLANNED PRIMARY EFFICACY EVALUATION & VARIABLE 
ORR will be the planned primary efficacy variable assessed by RECIST v1.1 (the planned efficacy 
evaluation). All patients who receive at least one dose of study treatment will be included in the primary 
efficacy analysis.  
 
6.3 
SECONDARY EFFICACY VARIABLES 
Secondary efficacy variables include: 
• 
PFS: Defined as the time from study drug initiation until progression event or death as assessed 
using the Kaplan-Meier method. 
• 
OS: Defined as time from study drug initiation to death as assessed using the Kaplan-Meier 
method. 
• 
DOR: Defined as the time from response to disease progression or death in patients who 
achieve complete or partial response.  
 

 
 
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6.4 
METHOD OF ANALYSIS 
The analysis of ORR will be performed according to the Simon two stage design using the prespecified 
stage-2 boundaries described in the Section 6.1 (Simon 1989). The null hypothesis that the true 
response rate is 5% will be tested against a one-sided alternative. In the first stage, 9 patients will be 
accrued. If there is no response in these 9 patients, the study will be stopped. Otherwise, 8 additional 
patients will be accrued for a total of 17. This design yields a type I error rate of 4.7% and power of 
81.2% when the true response rate is 25%. 
 
The analysis of time to event data, such as PFS and OS, will be performed using the all treated 
population with the Kaplan-Meier methodology. Safety data will be summarized descriptively. Adverse 
events will be summarized by severity, and relationship to study drug. The treatment outcomes of 
patients with EGFR-mutant non-small cell lung cancer (NSCLC) that has transformed into small cell 
lung cancer (SCLC) will be evaluated both as part of the overall data analysis and as a separate 
subgroup analysis. 
 
6.5 
ANALYSIS OF EXPLORATORY BIOMARKERS 
Exploratory analyses will be descriptive/graphical in nature and are designed to generate new 
hypotheses to be tested in future clinical studies. Continuous variables will be summarized with means 
and standard deviations. Dichotomous and categorical variables will be summarized using proportions 
with exact 95% confidence intervals and counts, respectively. These summaries will be computed for 
each treated patient at multiple time points before and initiation of study treatment as indicated on the 
study schema and study calendar. For each patient, comparisons in the pre- and post-study treatment 
responses will be compared using paired t-tests (or Wilcoxon signed rank tests if appropriate) for 
continuous variables and McNemar’s test for dichotomous or categorical variables. Associations 
between immune responses will be explored graphically (e.g. scatterplots, boxplots) and numerically 
(e.g. correlations, χ2 tests).  
 
7. 
INVESTIGATOR REQUIREMENTS 
7.1 
RETENTION OF RECORDS 
FDA regulations (21 CFR §312.62[c]) and the ICH Guideline for GCP (see Section 4.9 of the guideline) 
require that records and documents pertaining to the conduct of clinical trials and the distribution of 
investigational drug, patient records, consent forms, laboratory test results, and medication inventory 
records, must be retained for 2 years after the last marketing application approval in an ICH region or 
after at least 2 years have elapsed since formal discontinuation of clinical development of the 
investigational product. All state and local laws for retention of records also apply.  
 
7.2 
STUDY MEDICAL MONITORING REQUIREMENTS 
This clinical research study will be monitored both internally by the PI and externally by the Georgetown 
University IRB. In terms of internal review, the PI will continuously monitor and tabulate AEs. 
Appropriate reporting to the Georgetown University IRB will be made. The PI of this study will also 
continuously monitor the conduct, data, and safety of this study to ensure that: 
• 
Interim analyses occur as scheduled, 

 
 
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• 
Stopping rules for toxicity and/or response are met, 
• 
Risk/benefit ratio is not altered to the detriment of the subjects, 
• 
Appropriate internal monitoring of AEs and outcomes is done, 
• 
Over-accrual does not occur, 
• 
Under-accrual is addressed with appropriate amendments or actions,  
• 
Data are being appropriately collected in a reasonably timely manner. 
 
Routine monitoring will be carried out via a periodic team conference among investigators during which 
toxicity data, including all SAEs, will be reviewed and other issues relevant to the study such as interim 
assessment of accrual, outcome, and compliance with study guidelines, will be discussed. Monitoring 
will be carried out on an ongoing basis. The severity, relatedness, and whether or not the event is 
expected will be reviewed. 
 
7.2.1 
IRB 
GCP requires that the clinical protocol, any protocol amendments, the IB, the ICF and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and any other 
necessary documents must be reviewed by an IRB. Georgetown IRB approval of the protocol, ICF and 
subject information and/or advertising, as relevant, will be obtained prior to the authorization of drug 
shipment to a study site. Any amendments to the protocol will require IRB approval prior to 
implementation of any changes made to the study design. Any SAEs that meet the reporting criteria, as 
dictated by local regulations, will be reported to the IRB. During the conduct of the study, the 
investigator should promptly provide written reports to the IRB of any changes that affect the conduct of 
the study and/or increase the risk to subjects. 
 
7.2.2 
Data management and monitoring/auditing 
The Georgetown LCCC will be responsible for the data and safety monitoring of this trial. As this study is 
an investigator-initiated Phase 2 study, it is considered a high-risk study which requires real-time 
monitoring by the PI and study team, and regular reviews by the LCCC DSMC.  
All SAEs are required to be reported to Dr. Kim and the Georgetown University Lombardi Comprehensive 
Cancer Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office. In additions, SAEs should be 
reported to the local and/or to the Georgetown IRB per local IRB policy. Based on SAEs, the IRB retains 
the authority to suspend further accrual pending more detailed reporting and/or modifications to further 
reduce risk and maximize the safety of participating patients. 
Progress on the trial and the toxicities experienced will be reviewed by the LCCC DSMC on a quarterly 
basis from the time the first patient is enrolled on the study. Results of the DSMC meetings will be 
forwarded to the IRB and Macrogenics with recommendations regarding need for study closure. 
DSMC recommendations should be based not only on results for the trial being monitored, but also on 
data available to the DSMC from other studies (if applicable). It is the responsibility of the PI to ensure 
that the DSMC is kept apprised of non-confidential results from related studies that become available. It 
is the responsibility of the DSMC to determine the extent to which this information is relevant to its 
decisions related to the specific trial being monitored. 

 
 
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A written copy of the DSMC recommendations will be given to the trial PI and the IRB, and will be 
forwarded to representatives at Macrogenics. If the DSMC recommends a study change for patient safety 
or efficacy reasons, the PI must act to implement the change as expeditiously as possible. In the unlikely 
event that the PI and study team does not concur with the DSMC recommendations, then the LCCC 
Associate Director of Clinical Research must be informed of the reason for the disagreement. The PI, 
DSMC Chair, and the LCCC AD for Clinical Research will be responsible for reaching a mutually 
acceptable decision about the study and providing details of that decision to the IRB. Confidentiality must 
be preserved during these discussions. However, in some cases, relevant data may be shared with other 
selected trial investigators and staff to seek advice to assist in reaching a mutually acceptable decision. 
If a recommendation is made to change a trial for reasons other than patient safety or efficacy, the DSMC 
will provide an adequate rationale for its decision. If the DSMC recommends that the trial be closed for 
any reason, the recommendation will be reviewed by the Associate Director for Clinical Research at 
Georgetown University LCCC. Authority to close a trial for safety reasons lies with the IRB, with the above 
described input from DSMC and the AD for Clinical Research.  
Of note, if applicable, the DSMC will also review the safety data of the patients enrolled outside of 
Georgetown University. The data managers at each site will be entering data into the Georgetown 
database, so that all data will be available for the DSMC at Georgetown to review. De-identified source 
records should be sent via secure email to the Georgetown University Lombardi Comprehensive Cancer 
Center (LCCC) Consortium Investigator Initiated Trial (IIT) Office, as requested, and Dr. Chul Kim to 
confirm receipt of those records. 
 
7.3 
STUDY MEDICATION ACCOUNTABILITY 
The PI, as study sponsor, will ensure maintenance of complete and accurate records of the receipt, 
dispensation, and disposal or return of all study drug in accordance with 21 CFR, Part 312.57 and 
312.62 and Macrogenics requirements. 
All unused remaining product at the end of the study should be disposed of at the study site according 
to institutional standard operating procedure. If there is no standard operating procedure at the site for 
drug destruction, study drug will be returned to Macrogenics as directed. 
 
7.4 
DATA COLLECTION 
The study coordinator and investigators are responsible for ensuring that the eligibility checklist 
is completed in a legible and timely manner for every patient enrolled in the study, and that data are 
recorded on the appropriate forms and in a timely manner. Any errors on source data should be lined 
through, but not obliterated, with the correction inserted, initialed, and dated by the study coordinator or 
PI. All source documents will be available for inspection by the FDA and the Georgetown University 
IRB. 
 
8. 
ETHICAL CONSIDERATIONS 
8.1 
COMPLIANCE WITH LAWS AND REGULATIONS 
Patients who comply with the requirements of the protocol, are tolerating study treatment, and may be 
receiving benefit will be offered dosing beyond Cycle 1 at the investigator’s discretion after a careful 
assessment and thorough discussion of the potential risks and benefits of continued treatment with the 
patient. Such patients may have the option to receive treatment as long as they continue to experience 
clinical benefit in the opinion of the investigator until the occurrence of unacceptable toxicity, 

 
 
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symptomatic deterioration attributed to disease progression, or any of the other reasons for treatment 
discontinuation. 
 
8.2 
INFORMED CONSENT 
The informed consent document must be signed by the subject or the subject’s legally authorized 
representative before his or her participation in the study. The case history for each subject shall 
document that informed consent was obtained prior to participation in the study. A copy of the informed 
consent document must be provided to the subject or the subject's legally authorized representative. If 
applicable, it will be provided in a certified translation of the local language. 
Signed consent forms must remain in each subject’s study file and must be available for verification by 
study monitors at any time. 
8.3 
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
The PI is responsible for keeping the IRB apprised of the progress of the study and of any changes 
made to the protocol as deemed appropriate, but in any case, the IRB must be updated at least once a 
year. The PI must also keep the IRB informed of any significant AEs. 
Investigators are required to promptly notify their respective IRB of all adverse drug reactions that are 
both serious and unexpected. This generally refers to SAEs that are not already identified in the study 
therapy IB and that are considered possibly or probably related to the molecule or study drug by the 
investigator. Investigators must immediately forward to their IRB any written safety report or update 
provided by Macrogenics (e.g., IND safety report, IB, safety amendments and updates, etc.). 
 
8.4 
CONFIDENTIALITY 
Patient medical information obtained by this study is confidential and may be disclosed to third parties 
only as permitted by the ICF (or separate authorization to use and disclose personal health information) 
signed by the patient or unless permitted or required by law. 
Medical information may be given to a patient’s personal physician or other appropriate medical 
personnel responsible for the patient’s welfare for treatment purposes. 
Data generated by this study must be available for inspection upon request by representatives of the 
FDA and other regulatory agencies, national and local health authorities, Macrogenics representatives 
and collaborators, and the study site IRB if appropriate. 
 
9. 
STUDY DOCUMENTATION, MONITORING, AND ADMINISTRATION 
9.1 
STUDY DOCUMENTATION 
The investigator must maintain adequate and accurate records to enable the conduct of the study to be 
fully documented, including, but not limited to, the protocol, protocol amendments, ICFs and 
documentation of IRB/EC and governmental approval. In addition, at the end of the study, the 
investigator will receive the patient data, including an audit trail containing a complete record of all 
changes to data. 
 

 
 
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9.2 
PROTOCOL DEVIATIONS 
The investigator should document and explain any protocol deviations. The investigator should 
promptly report any deviations that might have an impact on patient safety and data integrity to the 
study sponsor (study PI) and to the IRB in accordance with established IRB policies and procedures. 
Please reference section 5.3 for submission of Protocol Deviations to the study sponsor (study PI). The 
sponsor will review all protocol deviations and assess whether any represent a serious breach of Good 
Clinical Practice guidelines and require reporting to health authorities. As per the sponsor's standard 
operating procedures, prospective requests to deviate from the protocol, including requests to waive 
protocol eligibility criteria, are not allowed. 
 
9.3 
PROTOCOL AMENDMENTS 
As study sponsor, any protocol amendments will be prepared by the PI. Protocol amendments will be 
submitted to the IRB and to regulatory authorities in accordance with local regulatory requirements. 
 
Approval must be obtained from the IRB and regulatory authorities (as locally required) before 
implementation of any changes, except for changes necessary to eliminate an immediate hazard to 
patients or changes that involve logistical or administrative aspects only (e.g., change in contact 
information). 

 
 
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10. 
REFERENCES 
Carvajal-Hausdorf D, Altan M, Velcheti V, et al. Expression and clinical significance of PD-L1, B7-H3, 
B7-H4 and TILs in human small cell lung Cancer (SCLC). J Immunother Cancer. 2019;7(1):65. 
 
Collins M, Ling V, Carreno BM. The B7 family of immune-regulatory ligands. Genome Biol. 
2005;6(6):223.  
 
de Miguel-Perez D, Russo A, Arrieta O, Ak M, Barron F, Gunasekaran M, Mamindla P, Lara-Mejia L, 
Peterson CB, Er ME, Peddagangireddy V. Extracellular vesicle PD-L1 dynamics predict durable 
response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer. 
Journal of Experimental & Clinical Cancer Research. 2022 Dec;41(1):1-4. 
 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
revised RECIST guideline (version 1.1). Eur J Cancer Oxf Engl 1990. 2009;45(2):228-247. 
 
Garst J. Topotecan: An evolving option in the treatment of relapsed small cell lung cancer. Ther Clin 
Risk Manag. 2007;3(6):1087-1095. 
 
Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the 
path forward. Nat Rev Cancer. 2017;17(12):725-737.  
 
Hofmeyer KA, Ray A, Zang X. The contrasting role of B7-H3. Proc Natl Acad Sci. 2008;105(30):10277-
10278.  
 
Investigator’s Brochure for MGC018, version 4.0 (October 20, 2021) 
 
National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program 
SEER*Stat Database: NPCR and SEER Incidence – U.S. Cancer Statistics Public Use Research 
Database, 2021 submission (2001–2019), United States Department of Health and Human Services, 
Centers for Disease Control and Prevention and National Cancer Institute.  
 
Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum–etoposide versus platinum–etoposide 
in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, 
open-label, phase 3 trial. The Lancet. 2019;394(10212):1929-1939.  
 
Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line 
treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol Off 
J Am Soc Clin Oncol. 2012;30(14):1692-1698.  
 

 
 
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Scribner JA, Brown JG, Son T, et al. Preclinical Development of MGC018, a Duocarmycin-based 
Antibody-drug Conjugate Targeting B7-H3 for Solid Cancer. Mol Cancer Ther. 2020;19(11):2235-2244. 
 
Seaman S, Zhu Z, Saha S, et al. Eradication of Tumors through Simultaneous Ablation of CD276/B7-
H3-Positive Tumor Cells and Tumor Vasculature. Cancer Cell. 2017;31(4):501-515.e8. 
 
Shenderov E, Mallesara GHG, Wysocki PJ, et al. 620P MGC018, an anti-B7-H3 antibody-drug 
conjugate (ADC), in patients with advanced solid tumors: Preliminary results of phase I cohort 
expansion. Ann Oncol. 2021;32:S657-S659.   
 
Simon R. Optimal two-stage designs for phase II clinical trials. Controlled clinical trials. 1989 Mar 1;10(1):1-0. 
 
Thomas PL, Groves SM, Zhang YK, et al. Beyond Programmed Death-Ligand 1: B7-H6 Emerges as a 
Potential Immunotherapy Target in SCLC. J Thorac Oncol. 2021;16(7):1211-1223. 
 
Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell 
lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654.  
 
Qiu M jun, Xia Q, Chen Y bing, et al. The Expression of Three Negative Co-Stimulatory B7 Family 
Molecules in Small Cell Lung Cancer and Their Effect on Prognosis. Front Oncol. 2021;11:600238. 
 
Xu H, Cheung IY, Guo HF, et al. MicroRNA miR-29 modulates expression of immunoinhibitory 
molecule B7-H3: Potential implications for immune based therapy of human solid tumors. Cancer Res. 
2009;69(15):6275-6281.  
 
Yang, Shuo, Wei Wei, and Qi Zhao. B7-H3, a checkpoint molecule, as a target for cancer 
immunotherapy. International journal of biological sciences 16.11 (2020): 1767. (11), 1767. 

  
 
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Appendix 1  
Study Flowcharts 
Table 1: Screening Procedural Outline 
Procedure 
Screening 
Visit 
(D-28 to D1) 
Notes 
Eligibility Assessments 
Informed Consent 
X 
Must be documented before any study-specific screening procedures are performed, and may be 
obtained >28 days prior to treatment initiation 
Inclusion/Exclusion 
Criteria 
X 
 
Medical History 
X 
 
Demographic Data 
X 
 
Baseline Assessments 
Con Medication Review 
X 
Medication (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or homeopathic 
remedies, nutritional supplements) used by a patient in addition to protocol-mandated treatment 
from 7 days prior to initiation of study treatment until the treatment discontinuation visit 
Vital Signs 
X 
Includes: temperature, heart rate, respiratory rate, blood pressure 
Weight 
X 
 
Height 
X 
 
Physical Exam 
X 
Includes evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, 
dermatological, musculoskeletal, respiratory, gastrointestinal, and neurological systems. Record 
abnormalities observed at baseline in the patient’s medical records 
ECOG Performance 
Status 
X 
 

  
 
70 
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Laboratory Testsa 
X 
CBC with differential, serum chemistry (bicarbonate/total carbon dioxide, sodium, potassium, 
chloride, glucose, BUN, creatinine, total protein, albumin, phosphorus, calcium, total bilirubin, 
alkaline phosphatase, ALT, AST), thyroid function (TSH, free/total T3, free T4) 
Pregnancy Test 
X 
Serum pregnancy test at screening for women of child-bearing potential onlyb 
Tumor Biopsyc 
X 
Mandatory for study entry 
Imaging Assessmentsd 
X 
CT (preferred) or MRI with contrast (unless contraindicated) of chest, abdomen and pelvis 
MRI (preferred) or CT of head with contrast (unless contraindicated) to assess for presence of CNS 
metastases 
aScreening laboratory test results must be obtained within 14 days of treatment initiation.  Screening labs that are performed outside the 14-day 
window for eligibility criteria may be repeated on C1D1, prior to treatment, to verify the subject continues to meet eligibility requirements. 
ba woman is defined as “of childbearing potential” if she is postmenarchal and has not reached post-menopausal state (≥12 continuous months of 
amenorrhea without identified cause other than menarche), and has not undergone surgical sterilization (removal of ovaries and/or uterus). 
cMust be performed ≥5 days prior to study treatment administration. If a biopsy is not feasible and/or safe, it may be waived after discussion with the 
principal investigator. In this case, we will obtain archival tissue if available. 
dimaging assessments performed as standard-of-care prior to obtaining study informed consent and within 28 days of study treatment initiation do 
not have to be repeated at screening. 
eMRI brain is required to confirm or refute diagnosis of CNS metastases in the event of equivocal CT scan. 
 
Table 2 – Study Calendar 
Procedure 
Treatment Cycles 
(28-day cycle) 
Treatment 
Discontinuation 
Follow-
up 
Cycle 1 D1 
and D15 
(±3 days) 
Cycle 2 D1 and 
D15 
(±3 days) 
Subsequent Cycles D1  
(±3 days) 
≤30 days after 
last treatment 
 
Clinical Assessment 
ECOG PS 
X 
X 
X 
X 
 
Vital Signsa 
X 
X 
X 
X 
 

  
 
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Weight 
X 
X 
X 
X 
 
Laboratory Testsb 
CBC w/ diff 
X 
X 
X 
X 
 
Chemistriesc 
X 
X 
X 
X 
 
Imaging Response Assessmentsd 
 
 
X 
 
 
Correlative Studies 
Peripheral bloode 
X (only on 
C1D1) 
 
X (only on C3D1) 
X 
 
Tumor biopsyf 
 
 
X 
 
Other Assessments 
Con Medsh 
X 
X 
X 
X 
 
Adverse Eventsi 
X 
X 
X 
X 
X 
Study Treatment administration 
X 
X 
X 
 
 
Survival follow-up and anti-cancer treatmentj 
 
 
 
 
X 
aincludes temperature, respiratory rate, heart rate, and blood pressure. For the first infusion, vital signs should be measured within 60 minutes prior 
to the infusion of MGC018, every 15 (± 5) minutes during MGC018 infusion if clinically indicated, and 30 (± 10) minutes after the infusion. For 
subsequent infusions, vital signs should be measured within 60 minutes prior to the infusion and, if clinically indicated or if symptoms occurred 
during the previous infusion, during and 30 (± 10) minutes after the infusion.  
bpre-treatment lab assessments do not have to be repeated if performed within 14 days of Cycle 1 D1, and within 3 days of D1 of all subsequent 
cycles. 
cchemistry includes: bicarbonate/total carbon dioxide, sodium, potassium, chloride, glucose, BUN, creatinine, total protein, albumin, phosphorus, 
calcium, total bilirubin, alkaline phosphatase, ALT, AST. 
dImaging assessments should be performed every two cycles within a -7 day window (i.e. imaging performed within 7 days of next scheduled 
treatment is acceptable) until radiographic disease progression per RECIST v1.1 or loss of clinical benefit. Tumor assessments should continue 
according to this schedule for patients who discontinue treatment for reasons other than disease progression or loss of clinical benefit. The same 
radiographic procedures used to assess disease sites at screening should be used for subsequent assessments (same contrast protocol for CT 
scans). CNS imaging only required if CNS metastases identified on screening imaging. If needed, CNS imaging should occur according to the 
same schedule as chest/abdomen/pelvis (CAP) imaging assessment.  

  
 
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eperipheral blood for correlative analyses will be drawn on day 1 of cycle 1, on day 1 of cycle 3, and upon disease progression/treatment 
discontinuation 
foptional biopsy upon progression of disease. Should be performed within 30 days of documented progression or prior to next anti-cancer therapy, 
whichever is sooner. 
hmedication (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by a patient 
in addition to protocol-mandated treatment from 7 days prior to initiation of study treatment until the treatment discontinuation visit. 
iafter informed consent has been obtained but prior to initiation of study treatment, only SAEs caused by a protocol-mandated intervention should 
be reported. After initiation of study treatment, all adverse events will be reported until 30 days after the last dose of study treatment or until 
initiation of new systemic anti-cancer therapy, whichever occurs first. SAEs will continue to be reported until 60 days after the last dose of study 
treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will be reported until 60 
days after last dose of study treatment regardless of initiation of new systemic anti-cancer therapy. After this period, all deaths, regardless of cause, 
should be reported. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is 
assessed as stable by the investigator, the patient is lost to follow-up, or the patient withdraws consent. Every effort should be made to follow all 
SAEs considered to be related to study treatment or trial-related procedures until a final outcome can be reported. 
jafter treatment discontinuation, information on survival follow-up and new anti-cancer therapy (including targeted therapy and immunotherapy) will 
be collected via telephone calls, patient medical records, and/or clinic visits approximately every 6 months (unless the patient withdraws consent or 
the Investigator terminates the study) for 2 years. If a patient requests to be withdrawn from follow-up, this request must be documented in the 
source documents and signed by the investigator. If the patient withdraws from study, the study staff may use a public information source (e.g., 
county records) to obtain information about survival status only. 
 

 
 
73 
 
Table 3 – Calendar of Biopsy and Peripheral Blood draws for correlative analyses 
Study Interval 
Time 
Sample 
Tumor Biopsya 
Pre-treatment 
≥5 days prior to C1 
Tumor tissue 
Disease progression (optional) 
≤30 days following documented 
disease progression 
Tumor tissue 
Peripheral blood 
Day 1 of Cycle 1 
Predose 
10 mL peripheral blood 
Day 1 of Cycle 3 
Predose 
10 mL peripheral blood 
Disease progression 
At visit 
10 mL peripheral blood 
aSee lab manual for information regarding tissue biopsy processing 
 
Table 4 – Calendar of Peripheral Blood draws for PK and ADA testing 
Cycle 
Day 
Timepoint 
Window 
PK: 
Total and 
ADC 
(serum) 
ADA: 
(serum) 
1 
1 
Pre-infusion 
N/A 
X 
X 
1 
1 
End of infusion 
+10 min 
X 
 
1 
15 
Day 15 
N/A 
X 
X 
2 
1 
Pre-infusion 
N/A 
X 
X 
2 
1 
End of infusion 
+10 min 
X 
 
2 
15 
Day 15 
N/A 
X 
 
3, 4, and 5 
1 
Pre-infusion 
N/A 
X 
X 
3, 4, and 5 
1 
End of infusion 
+10 min 
X 
 
6, 9, and 12 
1 
Pre-infusion 
N/A 
X 
X 
6, 9, and 12 
1 
End of infusion 
+10 min 
X 
 
IRRa 
N/A 
N/A 
N/A 
X 
X 
EOTV 
N/A 
EOTV 
N/A 
X 
X 
Note: Actual start of infusion times, EOI times, and PK/ADA sample collection times will be recorded on the 
eCRFs. Do not collect PK samples from infusion port. Pre-infusion PK samples may be collected before start of 
infusion on visit day (dosing day) or day before infusion. When collecting multiple samples, collect the PK sample 
first. 
aPK and ADA samples may be obtained at additional time points in participants who experience signs and 
symptoms of IRR. Samples should be obtained as soon as possible after onset of IRR, if feasible. 
 
 
 
  

 
 
74 
 
Appendix 1  
Calculation of Creatinine Clearance Using the Cockcroft-Gault Formula 
Creatinine Clearance (men) = (140-Age) × Lean Body Weight [kilograms] 
Serum Creatinine (mg/dL) × 72 
Creatinine Clearance (women) = 0.85 × (140-Age) × Lean Body Weight [kilograms] 
Serum Creatinine (mg/dL) × 72 
 
Source: Gault MH, Longerich LL, Harnett JD, et al. Predicting glomerular function from adjusted serum 
creatinine (editorial). Nephron 1992;62:249.

 
 
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Appendix 3  
Anaphylaxis Precautions 
EQUIPMENT NEEDED 
• 
Monitoring devices: ECG monitor, blood pressure monitor, oxygen saturation 
monitor, and thermometer 
• 
Oxygen 
• 
Epinephrine for intravenous, intramuscular, and endotracheal administration in 
accordance with institutional guidelines 
• 
Antihistamines 
• 
Corticosteroids 
• 
Intravenous infusion solutions, tubing, catheters, and tape 
 
PROCEDURES 
In the event of a suspected anaphylactic reaction during study treatment infusion, 
the following procedures should be performed: 
1. 
Stop the study treatment infusion. 
2. 
Call for additional medical assistance. 
3. 
Ensure that appropriate monitoring is in place, with continuous ECG and pulse 
oximetry monitoring, if possible. 
4. 
Administer antihistamines, epinephrine, or other medications as required by 
participant status and as directed by the physician in charge. 
5. 
Continue to observe the participant and document observations. 
6. 
Draw serum/plasma samples for immunogenicity testing. 
7. 
Ask participant to return for washout immunogenicity sample if appropriate