Phase II Trial of Magrolimab and Cetuximab With Pembrolizumab or Docetaxel for Recurrent/Metastatic Head Neck Squamous Cell Carcinoma
Phase: PHASE2
Conditions: Head Neck, Squamous Cell Carcinoma of Head and Neck
Sponsor: M.D. Anderson Cancer Center

 
MD Anderson Protocol Number: 2022-0903 
[2022-0903 
Amendment [02] Version Date [07.20.2023] 
 
 
PROTOCOL TITLE:  Phase II trial of magrolimab and cetuximab with pembrolizumab or 
docetaxel for recurrent/metastatic head neck squamous cell carcinoma 
 
 
Protocol Number (MD Anderson Cancer Center):  2022-0903 
 
Gilead Science Corresponding Protocol Reference Number: CO-US- 546-6366 
 
 
ClinicalTrials.gov Identifier:  TBD 
 
 
Principal Investigator:  Renata Ferrarotto, MD 
 
 
 
Version Number: 02 
 
 
Date: 7/20/2023 
 
 
IND #:  166539 
 
IND Sponsor: The University of Texas MD Anderson Cancer Center 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the recipient 
that no unpublished information contained herein will be published or disclosed without prior approval of the Principal 
Investigator. 
 

 
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Summary of Changes from Previous Version 
 
Affected 
Section(s)  
Summary of Revisions Made  
Rationale  
  5.5 
  Removal of DLT 
 For compliance issues  
  3.2  
Modification of Cohort B  
For compliance  
 9.2  
Sample Size Determination 
For budget compliance  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
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Version Date: 7/20/23 
 
 
 

 
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TABLE OF CONTENTS 
1 
Introduction ...................................................................................................................... 9 
 Study Rationale ............................................................................................................... 9 
 Background ...................................................................................................................... 9 
 Known Potential Risks ................................................................................................... 13 
 Correlative Studies Background .................................................................................... 13 
2 
Objectives ...................................................................................................................... 14 
 Primary Objectives ......................................................................................................... 14 
 Secondary Objectives .................................................................................................... 14 
 Exploratory Objectives ................................................................................................... 14 
3 
Study Design .................................................................................................................. 14 
 Cohort A ......................................................................................................................... 14 
 Cohort B ......................................................................................................................... 15 
4 
Study Population ........................................................................................................... 19 
 Number of Patients and Patient Selection ..................................................................... 19 
 Inclusion Criteria ............................................................................................................ 19 
 Exclusion Criteria ........................................................................................................... 21 
 Screen Failures .............................................................................................................. 23 
 Inclusion of Women and Minorities ................................................................................ 23 
5 
Treatment Plan ............................................................................................................... 23 
 Agent Administration ...................................................................................................... 24 
 Preparation/Handling/Storage/Accountability ................................................................ 32 
 IND Agent(S)/IDE Device(s) .......................................................................................... 32 
 Other Modality(ties) or Procedures ................................................................................ 32 
 Dose Expansion Cohorts ............................................................................................... 32 
 General Concomitant Medication and Supportive Care Guidelines .............................. 32 

 
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 Duration of Therapy ....................................................................................................... 33 
 Duration of Follow-up ..................................................................................................... 34 
 Dosing Delays/Dose Modifications ................................................................................ 34 
6 
Study Assessments and Procedures .......................................................................... 34 
 Schedule of Activities (SoA) .......................................................................................... 34 
 Screening phase ............................................................................................................ 38 
 Adverse Events .............................................................................................................. 38 
 Biomarker Assessments ................................................................................................ 39 
 Biospecimen repository ................................................................................................. 39 
 Safety Assessments ...................................................................................................... 39 
 End of Treatment (EOT) Visit ........................................................................................ 39 
 Long-term follow-up ....................................................................................................... 39 
 End of Study .................................................................................................................. 40 
7 
Adverse Event, Serious Adverse Event (SAE) ........................................................... 40 
 Definition of Adverse Events (AE) ................................................................................. 40 
 Adverse Event of Special Interest (AESI) ...................................................................... 42 
 Unexpected Adverse Events ......................................................................................... 43 
 Adverse Event Reporting Period ................................................................................... 45 
 Other events requiring reporting .................................................................................... 46 
8 
Response Criteria .......................................................................................................... 47 
 Measurement of Effect................................................................................................... 47 
 Evaluation of Target Lesions ......................................................................................... 47 
 Evaluation of Best Overall Response ............................................................................ 48 
 Duration of Response .................................................................................................... 48 
 Progression-Free Survival ............................................................................................. 49 
9 
Statistical Considerations ............................................................................................ 49 
 Safety and Feasibility Monitoring ................................................................................... 49 

 
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 Sample Size Determination ........................................................................................... 50 
 Stratification Factors ...................................................................................................... 53 
 Statistical Methods and Data Analysis .......................................................................... 54 
9.4.1  Analysis of Primary Efficacy Endpoint ......................................................................... 54 
9.4.2 Analysis of Secondary and Exploratory Endpoints ....................................................... 54 
10 
Study Oversight and Data Reporting Requirements ................................................. 55 
 Data and Safety Monitoring Committees ....................................................................... 55 
 Clinical Trial Monitoring ................................................................................................. 55 
 Study Records Retention ............................................................................................... 55 
 Consent Process and Documentation ........................................................................... 56 
11 
Data Management and Sharing Plan ........................................................................... 56 
 Data Type ...................................................................................................................... 56 
 Related Tools, Software and/or Code ........................................................................... 56 
 Standards ...................................................................................................................... 56 
 Data Preservation, Access, and Associated Timelines ................................................. 56 
 Access, Distribution, or Reuse Considerations ............................................................. 56 
 Data Collection and Management Responsibilities ....................................................... 57 
 Oversight of Data Management and Sharing ................................................................ 57 
 Genomic Data Sharing Plan .......................................................................................... 57 
 Incidental/Secondary Findings Disclosure Procedure ................................................... 57 
12 
Statement of Compliance ............................................................................................. 57 
13 
Refereces ....................................................................................................................... 57 
14 
Appendices .................................................................................................................... 59 
A. Guidance for the Management of Anemia, Blood Cross-Matching, and Packed Red Blood Cell 
Transfusion Procedure ........................................................................................................... 59 
B. Guidance for the Management of Infusion Reactions and Late Hypersensitivity Reactions60 
C. Management of Pneumonitis ............................................................................................. 62 

 
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LIST OF ABBREVIATIONS 
 
ADA 
Anti-drug Antibody 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase/ Serum Glutamic Pyruvic Transaminase 
ANC 
Absolute Neutrophil Count 
AST 
Aspartate Aminotransferase/ Serum Glutamic Oxaloacetic Transaminase 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CD47 
Cluster of Differentiation 47 
CNS 
Central Nervous System 
CR 
Complete Response 
CRF 
Case Report Form 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
Dose Limiting Toxicity 
DOR 
Duration of Response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HNSCC 
Head and Neck Squamous Cell Carcinoma 
IB 
Investigator’s Brochure 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IV 
Intravenously 
mAb 
Monoclonal Antibody 
OR 
Objective Response 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PD 
Progression of Disease 
PFS 
Progression Free Survival 
PK 
Pharmacokinetic 
PR 
Partial Response 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
RBC 
Red Blood Cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious Adverse Event 

 
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SD 
Stable Disease 
SIRP-α 
Signal Regulatory Protein Alpha 
SOC 
Standard of Care 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cells 

 
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STUDY SCHEMA 
 
 
  
1 
INTRODUCTION 
 
 Study Rationale 
Magrolimab is a first-in-class recombinant humanized mAb targeting the CD47-SIRP-α axis. 
Binding of magrolimab to human CD47 on-target malignant cells blocks the “don’t eat me” signal 
to macrophages and enhances tumor cell phagocytosis. In addition, magrolimab has the potential 
to elicit an antitumor T-cell response. In pre-clinical studies, strong synergistic antitumor activity 
was demonstrated when magrolimab is combined with EGFR antibodies with Fc receptor-
mediated immune effector activity, such as cetuximab. Furthermore, the combination of 
magrolimab with T-cell checkpoint inhibitors such as pembrolizumab can lead to enhanced 
antitumor activity. 
RESEARCH HYPOTHESIS 
Cohort A (anti-PD-1 naïve): The combination of magrolimab, cetuximab and pembrolizumab will 
be safe and increase objective response rate (ORR) when compared to reported ORR with 
pembrolizumab single agent or pembrolizumab plus cetuximab in the first-line setting. 
Cohort B (anti-PD-1 refractory): The combination of magrolimab, cetuximab, and docetaxel will 
increase ORR when compared to ORR with single agent cetuximab or docetaxel in patients who 
have progressed on first-line systemic therapy. 
 
 Background 
 
 Clinical Data with Cetuximab Plus Anti-PD1 in R/M HNSCC 
HNSCC is the sixth most common cancer worldwide. In 2020, there were more than 850,000 
cases leading to 440,000 deaths, according to The Global Cancer Observatory. The prognosis 

 
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of patients with R/M HNSCC is generally poor. The current standard-of-care first line systemic 
therapy is pembrolizumab single agent for patients with PD-L1 expression CPS of at least 1% or 
pembrolizumab combined with platinum and 5-FU, irrespective of PD-L1 status; nevertheless, 
median OS is still only 13 months (1). Pembrolizumab single agent has an attractive toxicity profile 
but only benefits approximately 17% of patients. Cetuximab is a monoclonal antibody (mAb) that 
targets EGFR but also can elicit immune functions such as antibody-dependent cell-mediated 
cytotoxicity involving NK cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell 
maturation (2). Currently, it is used in second or third line, following progression on anti-PD1 
and/or chemotherapy. While not specifically studied after progression on anti-PD1, the ORR with 
single agent cetuximab following progression on chemotherapy is 8-13% (3). 
There are two phase II studies evaluating the safety and efficacy of cetuximab with anti-PD1 in 
R/M HNSCC; both showing encouraging activity and an attractive toxicity profile(4, 5). In a phase 
II trial of pembrolizumab and cetuximab in 33 patients with platinum refractory or ineligible R/M 
HNSCC, mostly with oral cavity primary treated in the first-line setting, the reported ORR was 
45% (15/33), which compares favorably with the ORR of 17% achieved with pembrolizumab 
single agent in the same setting. The median DOR was of 14.9 months and median OS 18.4 
months. SAEs were observed in 3 (9%) patients, all grade 3: two patients developed grade 3 
mucositis and discontinued cetuximab only with clinical improvement, and one patient with grade 
3 colitis discontinued both treatments (5). 
On another phase II study investigating cetuximab and nivolumab in R/M HNSCC who had 
progressed on at least one line of systemic therapy, 51% of patients were PD-1 refractory and 
the ORR was 22.2% (10/43). The 1-year OS, the study primary endpoint, was 57% for patients 
not previously exposed to ICI versus 33% for those previously treated with anti-PD1. The most 
common grade 3 TRAE were fatigue (13%) and rash-acneiform (4.4%). The only grade 4 TRAE 
was cetuximab infusion reaction in 1 patient (2.2%)(4).  
Summary table of clinical efficacy data of prospective studies evaluating pembrolizumab 
(pembro), pembro plus chemotherapy (chemo), and pembro plus cetuximab in the first-line 
setting. 
1st line 
Pembrolizumab 
Pembrolizumab + 
Chemotherapy 
Pembrolizumab + 
Cetuximab 
ORR 
17% 
36% 
45% 
PFS 
2.3 m 
4.9 m 
NA 
OS 
11.6 m 
13 m 
18.4 m 
 
 Clinical Data with Taxanes With or Without Cetuximab in 2nd Line or Beyond in R/M 
HNSCC 
There is limited clinical data using taxanes as a single agent or in combination with cetuximab in 
R/M HNSCC who progressed after first line systemic therapy. Phase III studies using weekly 
docetaxel as the control arm in the HNSCC platinum-refractory setting have shown modest 
activity with an ORR of 6.2% (6). In two phase III randomized trials investigating anti-PD1 versus 

 
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standard of care (SOC) docetaxel, cetuximab or methotrexate in the second-line setting, the 
clinical outcomes to SOC therapy were: ORR 5.8-10%; PFS 2.3 months and OS = 5.1-7.1 months 
(7).  
In first line, taxane and cetuximab has shown encouraging activity in one single-arm phase II 
study, rendering an ORR of 54%, PFS of 4.2 months and OS of 8.1 months (8). Similar results 
have been reported by small, retrospective studies. There is no prospective data with taxane-
cetuximab combination in the platinum-refractory setting. Retrospective studies often include 
mixed patient populations, for instance, in a retrospective study including 42 patients with R/M 
HNSCC treated with paclitaxel and cetuximab, 40% were platinum-refractory and 38% were 
treated in the first-line setting; the reported ORR was 38%, with a median PFS of 3.9 months and 
OS of 7.6 months (9). 
Platinum-refractory 
(PD-1 naive) 
Cetuximab 
Docetaxel 
Cetuximab + taxane 
ORR 
8-13% 
6.2 % 
No prospective data; 
retrospective data with 
mixed population 
PFS 
2.3 m 
2.1 m 
OS 
5.9 m 
6 m 
 
The results of the EXTREME trial investigating the addition of cetuximab to platinum-5-FU (10) 
suggests that cetuximab has an additive effect when combined with chemotherapy (ORR 
increased from 20 to 36%); therefore, given that the ORR to docetaxel is approximately 6% in the 
platinum-refractory setting and the ORR to cetuximab is 8-13% in the same setting, it is 
reasonable to assume that the ORR to the docetaxel cetuximab combination is approximately 
20% in the second- or third- line setting for platinum-refractory patients.  
For patients treated with anti-PD1 as a single agent in first-line, it is expected that the ORR to 
the platinum-cetuximab doublet will be higher (~ 35% based on retrospective series), but no 
prospective data is available (11, 12).  
 
 Targeting CD47 with Magrolimab and Combining with EGFR or PD1 inhibitor 
Cluster of differentiation 47 (CD47) is a cell surface glycoprotein that inhibits phagocytosis by 
binding to the extracellular region of the inhibitory receptor signal regulatory protein alpha (SIRP-
α) on macrophages, recognized as “do not eat me signal” (13). CD47 via its interaction with 
SIRPα, serves as a myeloid specific immune checkpoint, protecting the cancer cells from being 
recognized and cleared by macrophages (13, 14). In cancer cells, CD47 transcript and protein 
expression is aberrantly upregulated and is an independent predictor of poor prognosis in patients 
with various cancer types (13).  
Magrolimab is a first-in-class recombinant humanized mAb targeting the CD47-SIRP-α axis. 
Binding of magrolimab to human CD47 on-target malignant cells blocks the “don’t eat me” signal 
to macrophages and enhances tumor cell phagocytosis. In addition, magrolimab has the potential 
to elicit an antitumor T-cell response.  

 
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In pre-clinical studies, strong synergistic 
antitumor activity was demonstrated when 
magrolimab is combined with EGFR 
antibodies 
with 
Fc 
receptor-mediated 
immune 
effector 
activity, 
such 
as 
cetuximab. Furthermore, the combination 
of magrolimab with T-cell checkpoint 
inhibitors such as pembrolizumab can lead 
to enhanced antitumor activity, which we 
have demonstrated in an HPV-positive 
oropharynx squamous cell carcinoma 
syngeneic 
mEER 
mouse 
model 
(unpublished data by Jagan Sastry PhD, 
Figure 1). CD47 blockade leads to tumor 
cell phagocytosis by macrophages and 
subsequent cross-presentation of tumor 
antigens by macrophages and other 
antigen presenting cells to CD8 T-cells, 
eliciting an adaptive immune cell response. 
Anti-PD-1 mAb enable enhanced T-cell 
activity by reversing T-cell exhaustion. 
Thus, the combination of magrolimab with 
an anti-PD-1 can lead to an enhanced T-
cell antitumor response through these 
complementary mechanisms of action. 
 
 Magrolimab Clinical Pharmacology 
Details of magrolimab clinical pharmacology and pre-clinical studies using magrolimab are 
available in the Investigator’s brochure (IB). In vitro studies of magrolimab, showed high binding 
affinity to monomeric and bivalent human CD47 antigen with a dissociation constant (Kd) of 8 × 
10−9 and 8 × 10−12 M, respectively. Expression of CD47 was observed on human peripheral blood 
cells, and magrolimab did not trigger phagocytosis by human macrophages of normal red blood 
cells (RBCs) or normal human bone marrow cells in vitro but was a potent inducer of phagocytosis 
of CD47-expressing AML cells in vitro. The combination of magrolimab and avelumab effectively 
enhanced phagocytosis of ovarian cancer cells by human macrophages compared with 
magrolimab or avelumab alone.  
Nonclinical in vivo pharmacology studies using xenograft cancer models provide compelling 
evidence that magrolimab triggers phagocytosis and elimination of cancer cells from multiple 
human solid tumors and hematologic malignancies. Overall, magrolimab in combination with 
azacitidine, trastuzumab, rituximab, cetuximab, and panitumumab demonstrated additive effect 
on eliminating cancer cells in a variety of nonclinical cancer models, resulting in a long-term 
remission and increased survival of animals. 
mEER: mouse oral epithelial cells expressing 
HPV-16 E6 and E7 along with H-RAS. CCD47 is 
expressed by mEER tumor cells.  

 
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Clinical pharmacokinetic (PK) have been analysed in all studies of magrolimab, alone or in 
combination, thus far. A nonlinear PK consistent with target-mediated clearance has been 
observed. Overall, 2-11% of patients tested positive for antidrug antibody (ADA) against 
magrolimab, however positivity had no impact on PK or clinical safety in these patients (SCI-
CD47-001; SCI-CD47-002). 
Preliminary PK data of magrolimab from other ongoing studies (5F9003, 5F9004, and 5F9005) 
indicate similar PK properties across all tumor populations and in the presence of co-administered 
drugs. A preliminary population PK analysis of combined magrolimab PK data indicated that 
results for magrolimab population PK were typical of other nonlinear antibodies. No clinically 
significant covariates of PK variability were identified. 
 
 Magrolimab Preliminary Clinical Data  
The safety and preliminary activity of the combination of magrolimab with cetuximab is being 
evaluated in patients with solid tumors and colorectal cancer (SF9004). A total of 78 patients have 
been treated with this regimen and no dose limiting toxicities (DLTs) were identified (15). 
The combination of magrolimab and the anti-PD-L1 avelumab is also being studied in solid tumors 
and ovarian cancer (SF9006) (16). Similarly, no DLTs were seen with the combination.  
In both trials, cetuximab and avelumab standard doses are being used, with two maintenances 
doses of magrolimab being investigated: 30 and 45 mg/Kg.   
The most common adverse events associated with magrolimab are fatigue (43%; 2.8% severe), 
anemia (40%, 22% severe), headache (36%; 1.4% severe), and infusion reactions (22%; 3.1% 
severe). 
The main on-target toxicity of magrolimab is anemia, which does not overlap with cetuximab or 
anti-PD1; therefore, we envision the triplet will be well-tolerated. Magrolimab induced-anemia 
typically manifests as a decline in hemoglobin within the first 2 weeks of treatment followed by a 
compensatory reticulocytosis, with many patients experiencing a gradual return to baseline 
despite continued dosing. Administration of a low priming dose of magrolimab mitigated on-target 
anemia and will be utilized in this trial. Further details of completed and ongoing clinical trials 
investigating magrolimab as a single agent or in combination with other agents are available in 
the Investigator’s brochure (IB). 
 
 Known Potential Risks 
Please refer to Investigator’s brochure (IB) for known potential risks of magrolimab from either 
clinical or nonclinical studies.   
 
 Correlative Studies Background 
N/A 

 
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2 
OBJECTIVES 
 
 Primary Objectives 
Objective response rate (ORR) per RECIST v1.1  
 
 Secondary Objectives 
- 
Adverse events rates per CTCAE V5.0 (appendix) 
- 
Duration of response (DOR) 
- 
Progression free survival (PFS) per RECIST v1.1  
- 
Overall survival (OS) per RECIST v1.1 
 
 Exploratory Objectives 
Assessment of blood and tissue-based biomarkers predictive of response to therapy 
 
3 
STUDY DESIGN 
 
This is a two-arm, phase II, open-label study designed to evaluate the safety and activity of 
magrolimab, cetuximab, and pembrolizumab administered in first-line (cohort A) or magrolimab, 
cetuximab, and docetaxel administered in second or third line for PD-1-refractory (cohort B) R/M 
HNSCC patients. According to the United Stated prescribing information for pembrolizumab, 
Cohort A will only enroll patients with PD-L1 expressing tumors (combined positive score [CPS] 
≥ 1); while cohort B will enroll patients irrespective of PD-L1 CPS status. The primary outcome is 
the ORR per RECIST v1.1 (17). The study will characterize the safety profile of the triplet therapies 
(safety run-in cohort). The efficacy will be evaluated by applying the Bayesian Optimal Phase 2 
(BOP2) design {Zhou, 2017 #5879} 
 Cohort A  
Anti-PD1 naïve patients will be administered concurrent systemic therapy with pembrolizumab 
200 mg IV Q3W, cetuximab loading dose of 400 mg/m2 followed by 250 mg/m2 IV QW, and 
magrolimab 1mg/kg priming dose followed by weekly doses of 30 mg/Kg IV (Dose 0). Dose 
limiting toxicity (DLT) will be assessed during the first 2 cycles (6 weeks). If DLTs occur in > 2 out 
of the first 6 patients enrolled, magrolimab will be dose reduced as per Table 3. After 2 cycles of 
therapy (6 weeks), if objective response or stable disease is documented on scans, patients will 
be transitioned to the maintenance phase. To mitigate the risk of infusion-related reactions (IRR), 
a staggered phase will be implemented during the safety run-in (6-12 patients). As per Study 
Schema, during cycle 1, patients will receive magrolimab plus pembrolizumab; cetuximab will be 
added during cycle 2. After the safety run-in, if there is no increase in risk of IRR, the staggered 
phase may be eliminated. 

 
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 Cohort B 
Patients who have experienced cancer progression with anti-PD-1 as a single agent or combined 
with chemotherapy will be administered cetuximab loading dose of 400 mg/m2 followed by 250 
mg/m2 IV QW, magrolimab 1 mg/Kg priming dose followed by maintenance doses of 30 mg/Kg 
IV QW, and weekly docetaxel 30 mg/m2 IV QW (Dose 0). Docetaxel will be administered only for 
6 to 12 weeks (2 to 4 cycles), followed by maintenance cetuximab and magrolimab doublet if 
objective response or stable disease is documented on scans after 2 to 4 cycles of the triplet 
therapy. If DLTs occur in > 2 out of the first 6 patients enrolled during the first 2 cycles (6 weeks), 
magrolimab will be dose reduced as per Table 3. To mitigate the risk of infusion-related reactions 
(IRR), a staggered phase will be implemented during the safety run-in (6-12 patients). As per 
Study Schema, during cycle 1, patients will receive magrolimab plus cetuximab; docetaxel will be 
added during cycle 2. After the safety run-in, if there is no increase in risk of IRR, the staggered 
phase may be eliminated. 
Table 3. Magrolimab Dosing 
3A.Magrolimab Dosing for Cohort A 
Magrolimab 
1 mg/Kg IV (3 hours ± 30 min) 
Cycle (C) 1 Day (D) 1 
Magrolimab starting dose level 
30 mg/Kg IV (2 hours ± 30 min) 
QW beginning at C1D8 and onward during the 
Staggered and Induction phases (5 weeks) 
Magrolimab 
30 mg/Kg IV (2 hours ± 30 min) 
Q2W during the Maintenance phase (C3D1 
onward) 
Magrolimab de-escalation, Level -1 
20 mg/Kg IV (2 hours ± 30 min) 
QW beginning at C1D8 and onward during the 
Staggered and Induction phases (5 weeks) 
Q2W during the Maintenance phase (C3D1 
onward) 
Magrolimab de-escalation, Level -2 
15 mg/Kg IV (2 hours ± 30 min) 
QW beginning at C1D8 and onward during the 
Staggered and Induction phases (5 weeks) 
Q2W during the Maintenance phase (C3D1 
onward) 
 
3B. Magrolimab Dosing for Cohort B 
 
Magrolimab 
1 mg/Kg IV (3 hours ± 30 min) 
Cycle (C) 1 Day (D) 1 
Magrolimab starting dose level 
30 mg/Kg IV (2 hours ± 30 min) 
QW beginning at C1D8 and onward during the 
Staggered and Induction phases (8-14 weeks) 

 
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Magrolimab 
30 mg/Kg IV (2 hours ± 30 min) 
Q2W during the Maintenance phase 
Magrolimab de-escalation, Level -1 
20 mg/Kg IV (2 hours ± 30 min) 
QW beginning at C1D8 and onward during the 
Staggered and Induction phases (8-14 weeks) 
Q2W during the Maintenance phase 
Magrolimab de-escalation, Level -2 
15 mg/Kg IV (2 hours ± 30 min) 
QW beginning at C1D8 and onward during the 
Staggered and Induction phases (8-14 weeks) 
Q2W during the Maintenance phase 
 
DLT Definition and Exceptions for Safety Run-in 
A DLT for the safety run-in is defined as the occurrence of any ≥ Grade 3 toxicity (according to 
NCI-CTCAE v 5.0) with the exceptions below. 
The following are exceptions to the DLT definition and are NOT considered a DLT:  
•  Grade 3 anemia; however, Grade 3 hemolytic anemia that is medically significant, requiring 
hospitalization or prolongation of existing hospitalization, disabling, or limiting self-care 
activities of daily life is considered a DLT.  
•  Grade 3 neutropenia that resolves to Grade 2 within 3 weeks with supportive care measures 
(ie, granulocyte colony-stimulating factor) or Grade 4 neutropenia lasting for 7 days or less with 
supportive measures.  
•  Grade 3 thrombocytopenia in the absence of clinically significant bleeding that resolves to 
Grade 2 or pretreatment baseline within 3 weeks.  
•  Grade 3 indirect/unconjugated hyperbilirubinemia that resolves to ≤ Grade 2 with supportive 
care within 1 week and is not associated with other clinically significant consequences.  
•   Isolated Grade 3 electrolyte abnormalities that resolve to ≤ Grade 1 with supportive care within 
72 hours and are not associated with other clinically significant consequences 
•  Grade 3 elevation in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) 
and/or alkaline phosphatase.  
•  Grade 3 nausea, vomiting, or diarrhea that resolves to ≤ Grade 2 with supportive care within 
72 hours.  
•  Grade 3 fatigue that resolves to ≤ Grade 2 within 2 weeks on study.  
•  Grade 3 magrolimab, pembrolizumab, or cetuximab infusion reactions in the absence of an 
optimal pretreatment regimen, which is defined as acetaminophen or a comparable 
nonsteroidal anti-inflammatory agent plus, an antihistamine and corticosteroids.  
•  Grade 3 or 4 lymphopenia or leukopenia not associated with other clinically significant 
consequences.  
•  Transient (≤ 48 hours) Grade 3 local reactions, flu-like symptoms, myalgias, fever, headache, 
acute pain, or skin toxicity that resolves to ≤ Grade 2 within ≤ 72 hours after medical 

 
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management (eg, supportive care, including immunosuppressant treatment) has been 
initiated.  
•  Tumor flare phenomenon, defined as local pain, irritation, or rash localized at sites of known or 
suspected tumor, that resolves within 72 hours with supportive care measures.  
•  Grade 3 lipase and/or amylase elevation without clinical or radiologic evidence of pancreatitis. 
• Grade 3 or 4 events clearly associated with the underlying disease, disease progression, 
concomitant medication, or comorbidity 
Throughout treatment in Cohort A and B, dose reduction will be allowed for cetuximab, docetaxel 
and magrolimab due to treatment-related adverse events as outlined in the table below and 
detailed in section 5 “Treatment Plan”. There will be no dose adjustment for pembrolizumab. The 
use of prophylactic growth factor is allowed on Cohort B. 
Table 4 Dose de-escalation for Safety Run-in 
 
Initial dose 
Dose 
reduction 1 
Dose 
reduction 2 
Cetuximab Q1W 
250 mg/m2 
200 mg/m2 
150 mg/m2 
Cetuximab Q2W 
500 mg/m2 
400 mg/m2 
300 mg/m2 
Docetaxel Q1W 
30 mg/m2 
25 mg/m2 
20 mg/m2 
Magrolimab Q1W 
30 mg/Kg 
20 mg/Kg 
15 mg/Kg  
Magrolimab Q2W 
30 mg/Kg 
20 mg/Kg 
15 mg/Kg 
 
During Cycle 1 (C1) only, magrolimab will be administered on D1 and cetuximab and 
pembrolizumab (Cohort A) or cetuximab and docetaxel (Cohort B) will be administered on D2. 
During C1 days 8 and 15 and from cycle 2 on, all three drugs in both cohorts can be administered 
the same day.   
In both arms, magrolimab and cetuximab Q2W can be used during maintenance (cetuximab 500 
mg/m2 and magrolimab 30 mg/Kg) based on emerging data from ongoing trials (18, 19). If a Q2W 
schedule is entertained, pembrolizumab can be administered at 400 mg Q6W in Cohort A after at 
least 2 cycles or 6 weeks of weekly treatment. Treatment in both arms will be continued until 
disease progression, unacceptable side effects, or after 2 years (~104 weeks). 
 
Cohort A: Maintenance Period Assessment 
Procedures 
Maintenance Period  (6-week cycle) 
Cycle 
3 
4+ 
EOTm 
Day 
D1 (±1d) 
D8 (±1d) 
D15 (±1d) 
D22 (±1d) 
D29 (±1d) 
D36 (±1d) 
D1 (±1d) 
D8 (±1d) 
D15 (±1d) 
D22 (±1d) 
D29 (±1d) 
D36 (±1d) 
Concurrent meds 
X -------------------------------------------------------  X 
  

 
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Physical exam 
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
Vital signs 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Weight 
X 
  
 X 
  
X  
  
X 
  
X  
  
X  
  
X 
Pregnancy testh 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Perfomance Status 
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
Adverse Events 
X -------------------------------------------------------  X 
X 
Magrolimaba 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
Cetuximabb 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
Pembrolizumabc 
X 
  
  
  
  
  
X 
  
  
  
  
  
  
CBC w/diff, chemistry 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
Thyroid Functiond 
X 
  
  
  
  
  
X 
  
  
  
  
  
  
Imaginge 
X 
  
  
  
  
  
Xe 
  
  
  
  
  
  
a Magrolimab 30mg/kg Q2W 
b Cetuximab 500mg/m2 Q2W 
c Pembrolizumab 400mg Q6W 
d Thyroid function will consist of TSH and free T4; Thyroid function will be repeated every cycle. 
e Imaging will be performed every 1 cycle (6 weeks) ± 1 week. 
h Pre-menopausal female subjects of childbearing potential only. Pregnancy test should be done within 14 days of 
starting therapy during screening and every 6 weeks (+/- 14 days) during trial therapy 
m EOT=End of treatment. The EOT Visit will occur with disease progression, unacceptable side effects, or after 2 years 
of systemic therapy at least 90 days after the last dose of study therapy for Cohort A and at least 30 days after the last 
dose of study therapy for Cohort B. After the EOT evaluation, information on additional oncologic treatment, time to 
disease progression/recurrence, sites of recurrence, additional therapies, long-term survival, and other relevant clinical 
data may be obtained. Patients (or their family members or designees) may be contacted by telephone or in writing or 
by electronic mail or during clinic visits after treatment discontinuation for collection of long-term follow-up data. Long-
term follow-up clinical information may also be obtained through chart reviews. 
 
Cohort B: Maintenance Period Assessment 
 
 
Procedures 
Maintenance Period  (6-week Cycle) 
Cycle 
5 
6+ 
EOTm 
Day 
D1 (±1d) 
D8 (±1d) 
D15 (±1d) 
D22 (±1d) 
D29 (±1d) 
D36 (±1d) 
D1 (±1d) 
D8 (±1d) 
D15 (±1d) 
D22 (±1d) 
D29 (±1d) 
D36 (±1d) 
Concurrent meds 
X -------------------------------------------------------  X 
  
Physical exam 
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
Vital signs 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Weight 
X 
  
X  
  
X  
  
X 
  
X  
  
X  
  
X 
Pregnancy testh 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Perfomance Status 
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
Adverse Events 
X -------------------------------------------------------  X 
X 
Magrolimaba 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
Cetuximabb 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  

 
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CBC w/diff, chemistry 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
Thyroid Functiond 
X 
  
  
  
  
  
X 
  
  
  
  
  
  
Imaginge 
X 
  
  
  
  
  
Xe 
  
  
  
  
  
  
a Magrolimab 30mg/kg Q2W 
b Cetuximab 500mg/m2 Q2W 
c Thyroid function will consist of TSH and free T4; Thyroid function will be repeated every cycle. 
d Imaging will be performed every 1 cycle (6 weeks) ± 1 week. 
h Pre-menopausal female subjects of childbearing potential only. Pregnancy test should be done within 14 days of 
starting therapy during screening and every 6 weeks (+/- 14 days) during trial therapy 
m EOT=End of treatment. The EOT Visit will occur with disease progression, unacceptable side effects, or after 2 years 
of systemic therapy at least 90 days after the last dose of study therapy for Cohort A and at least 30 days after the last 
dose of study therapy for Cohort B. After the EOT evaluation, information on additional oncologic treatment, time to 
disease progression/recurrence, sites of recurrence, additional therapies, long-term survival, and other relevant clinical 
data may be obtained. Patients (or their family members or designees) may be contacted by telephone or in writing or 
by electronic mail or during clinic visits after treatment discontinuation for collection of long-term follow-up data. Long-
term follow-up clinical information may also be obtained through chart reviews. 
 
Imaging will be performed at baseline and every 6 weeks (± 1 week). Tumor and blood for 
correlative studies will be collected at baseline and prior to cycle 3 day 1 (C3D1). Additional blood 
samples will be collected on C2D1, and at the time of progression. A tumor biopsy will be strongly 
encouraged but optional at progression. 
 
4 
STUDY POPULATION 
 
 Number of Patients and Patient Selection 
The target population for this study are patients with R/M HNSCC. Up to 61 patients may be 
enrolled in the study, with up to 31 patients in Cohort A and up to 30 patients in Cohort B. The 
maximum sample size includes both the safety run-in part and the Phase II part of the study if a 
DLT is observed in both cohorts. If no DLT is observed during the safety run-in part in neither 
cohort, the maximum number of efficacy evaluable patients enrolled will be 49 (25 in Cohort A 
and 24 in Cohort B). 
 Inclusion Criteria 
All Patients 
All patients must meet all of the following inclusion criteria to be eligible for participation in this 
study: 
1) 
Patient must have a diagnosis of recurrent or metastatic oropharynx, oral cavity, 
hypopharynx, or larynx squamous cell carcinoma (HNSCC), not amenable to curative-
intent local therapy with known PD-L1 CPS determined by an FDA-approved test. 
2)        Patient has provided informed consent. 
3) 
Patient is willing and able to comply with clinic visits and procedures outlined in the study 
protocol. 
4) 
Male or female ≥ 18 years of age 

 
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5) 
ECOG performance status of 0 or 1 
6) 
Laboratory measurements, blood counts: 
a. Hemoglobin ≥ 9 g/dL within 24 hours prior to initial dose of study treatment. Red blood 
cell transfusions are permitted to meet the hemoglobin inclusion criteria, within limits 
set per exclusion criterion 6. 
b. Absolute neutrophil count ≥ 1.2 x 109/mL 
c. Platelets ≥ 100 x 109/mL 
7) 
Laboratory measurements, renal function: 
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or if elevated, a calculated glomerular 
filtration rate > 40 mL/min/1.73m2 per CKD-EPI equation. 
8) 
Laboratory measurements, hepatic function: 
a. AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver metastases 
b. Total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN and primarily unconjugated if patient has a 
documented history of Gilbert’s syndrome or genetic equivalent 
 9) 
Laboratory measurements, coagulation function: 
a. International normalized ratio or prothrombin time (PT) ≤ 1.5 x ULN unless patient is 
receiving anticoagulation therapy, as long as PT or partial thromboplastin time (PTT) is 
within therapeutic range of intended use for anticoagulants 
b. Activated partial thromboplastin time or PTT ≤ 1.5 x ULN unless patient is receiving 
anticoagulation therapy, as long as PT or PTT is within therapeutic range of intended 
use for anticoagulants 
10) 
Female patients with reproductive potential must practice two effective contraceptive 
measures for the duration of study drug therapy and for at least 6 months after completion 
of study therapy. The two birth control methods can be either two barrier methods or a 
barrier method plus a hormonal method to prevent pregnancy. The following are 
considered adequate barrier methods of contraception: diaphragm, condom, copper 
intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will 
include any registered and marketed contraceptive agent that contains an estrogen and/or 
a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular 
agents). 
11) 
Male patients who are sexually active with women with reproductive potential must agree 
to use contraception for the duration of treatment and for at least 6 months after completion 
of study therapy. 
12) 
Measurable disease according to RECIST, version 1.1 
13) 
Patients must be willing to provide baseline tumor tissue from a core or excisional biopsy 
(fine needle aspirate is not adequate). A newly obtained biopsy (within 90 days prior to 
study treatment start) is strongly preferred, but an archival sample is acceptable.  

 
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14)  
Absence of active auto-immune disease or any other contra-indication to pembrolizumab, 
cetuximab, docetaxel or magrolimab 
 
Cohort A:  
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Cohort 
A must fulfill the following cohort-specific inclusion criteria: 
15) 
PD-L1 CPS must be ≥ 1 
16)    Patients should not have had prior systemic therapy administered in the recurrent or 
metastatic setting. Systemic therapy that was completed more than 3 months prior to 
signing consent if given as part of multimodal treatment for locally advanced disease is 
allowed. 
 
Cohort B:  
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Cohort 
B must fulfill the following cohort-specific inclusion criterion: 
17) 
Patients must have received at least 1 and no more than 2 lines of prior systemic 
anticancer therapy in the recurrent/metastatic setting not including docetaxel but including 
anti-PD1. Patients must have progressed on anti-PD1 (radiographically or clinically) or 
developed intolerable adverse events attributed to anti-PD1 that lead to treatment 
discontinuation and eventual disease progression.  
 
 Exclusion Criteria 
All Patients 
Patients who meet any of the following exclusion criteria are not eligible to be enrolled in this 
study: 
1) 
Prior radiation therapy (or other nonsystemic therapy) within 2 weeks prior to enrollment 
2) 
Patient has not fully recovered (ie, ≤ Grade 1 at baseline) from AEs due to a previously 
administered treatment. 
a. Note: Patients with ≤ Grade 2 neuropathy, alopecia, or laboratory values in inclusion 
criteria 5 through 8 are exceptions to this criterion and may qualify for the study. 
b. Note: If a patient received major surgery, he or she must have recovered adequately 
from the toxicity and/or complications from the intervention prior to starting therapy. 
3) 
Active CNS disease (patients with asymptomatic and stable, treated CNS lesions who 
have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks 
are not considered active) 
4) 
Red blood cell transfusion dependence, defined as requiring more than 2 units of packed 
RBC transfusions during the 4-week period prior to screening. Red blood cell transfusions 

 
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are permitted during the screening period and prior to enrollment to meet the hemoglobin 
inclusion criterion. 
5) 
History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the 
last 3 months 
6) 
Known inherited or acquired bleeding disorders 
7) 
Prior treatment with CD47 or SIRPα-targeting agents 
8) 
Prior anticancer therapy including, but not limited to, chemotherapy, immunotherapy, or 
investigational agents within 4 weeks prior to magrolimab treatment 
9) 
Life expectancy of less than 3 months and/or rapidly progressing disease (eg, tumor 
bleeding, uncontrolled tumor pain) in the opinion of the treating investigator 
10) 
Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form of 
immunosuppressive therapy within 7 days prior to the first dose of study therapy. 
Corticosteroid use as a premedication for biopsy, allergic reactions or for prophylactic 
management of AEs related to the chemotherapies specified in the protocol is allowed. 
The use of physiologic doses of corticosteroids may be approved with approval by the 
sponsor. 
11) 
Active autoimmune disease that has required systemic treatment in the past 2 years (ie, 
use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). 
Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement 
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic 
treatment. 
12) 
Prior allogeneic tissue/solid organ transplant 
13) 
Current participation in another interventional clinical study 
14) 
History of previous malignancy other than malignancy treated with curative intent and with 
no evidence of active disease ≥ 2 years before the first dose of the study drugs and of low 
potential risk for recurrence. Patients with the following diagnoses represents an exception 
and may enroll:  
a. Non-melanoma skin cancers with no current evidence of disease 
b. Melanoma in situ with no current evidence of disease 
c. Localized cancer of the prostate with prostate-specific antigen of <1 ng/mL 
d. Treated or localized well-differentiated thyroid cancer 
e. Treated cervical carcinoma in situ 
f. 
Treated ductal/lobular carcinoma in situ of the breast 
 
15) 
Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or 
anti-fungal therapy ≤ 10 days prior to administration of investigational product. Patients 
with known hepatitis B, hepatitis C (HCV), or HIV infection could go on study provided the 
viral load is undetectable at Screening. 

 
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16) 
Significant disease or medical conditions, as assessed by the investigator and sponsor, 
that would substantially increase the risk-benefit ratio of participating in the study. This 
includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable 
angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart 
failure New York Heart Association Class III-IV 
17) 
Female subjects who are pregnant or breast-feeding  
18) 
Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient 
 
 Screen Failures 
Participants who are consented to participate in the clinical trial, who do not meet one or more 
criteria required for participation in the trial during the screening procedures, are considered 
screen failures. 
 
 Inclusion of Women and Minorities 
Both men and women of all races and ethnic groups are eligible for this trial.     
5 TREATMENT PLAN 
Investigational medicinal product (IMP) is defined as magrolimab + cetuximab + pembrolizumab 
combination in cohort A, and magrolimab + cetuximab + docetaxel in cohort B. Details of each 
IMP component to be administered are shown in Table 5.   
Table 5 
Intervention name 
Magrolimab 
Pembrolizumabb 
Type  
Biologic 
Biologic 
Dose formulation 
Concentrate for solution for infusion 
Concentrate for solution for infusion 
Unit dose strength(s) 
20 mg/mL 
25 mg/mL 
Dosage level(s) a 
1 mg/kg priming dose 
30 mg/Kg every week 
200 mg every 3 weeks 
Route of administration 
IV infusion over 3 hours (first infusion); 
and over 2 hours for subsequent 
infusions. Prior to administration of 
drugs.  
IV infusion over 30 minutes through an 
IV line containing a sterile 0.2 micron to 
5 micron in-line or add-on filter 
Packaging and labeling 
Supplied in a single-dose vial in a 
treatment box. Each vial contains 20 
mg/mL and has an extractable volume of 
10 mL. Each vial and treatment box will 
be labeled as required per country 
requirement. 
Supplied in a single-dose vial in a 
treatment box. Each vial contains 100 
mg/4 mL (4 mL). Each vial and 
treatment box will be labeled as 
required per country requirement. 
Current names or aliases Not applicable 
Keytruda® 
Intervention name 
Cetuximabb 
Docetaxelb 
Type  
Biologic 
Cytotoxic anticancer drug 
Dose formulation 
Concentrate for solution for infusion 
Concentrate for solution for infusion 

 
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Unit dose strength(s) 
20 mg/mL 
20 mg/mL 
Dosage level(s)a  
400 mg/m2 loading dose 
250 mg/m2 weekly 
30 mg/m2 weekly 
Route of administration 
IV infusion over 120-min (loading dose); 
and 
over 
60-min 
for 
subsequent 
infusions.  
IV infusion over 60 minutes through an 
IV line containing a sterile 0.2 micron to 
5 micron in-line or add-on filter 
Packaging and labeling 
100 mg/50 mL, single-use vial OR 200 
mg/100 mL, single-use vial.  
Single use vials 20 mg/mL, 80 mg/4 mL, 
or 160 mg/8 mL 
Current names or aliases Erbitux® 
Taxotere® 
a The total dose will be calculated based on the weight on the day of the infusion or the most recent weight assuming it was assessed 
in a reasonable time frame according to Investigator assessment.  b, Pembrolizumab, cetuximab, and docetaxel are commercially 
sourced. Information regarding their formulation can be found in the current country-specific prescribing information. 
 
 
 Agent Administration 
5.1.1 Magrolimab  
5.1.1.1 Packaging and Labeling 
Formulation: magrolimab is provided as a 20 mg/mL concentrate for solution for infusion in a 
single-dose vial with an extractable volume of 10 mL. For magrolimab preparation, handling, and 
storage, refer to Appendix D. 
Route of administration: intravenous (IV) infusion. 
Dose regimen: First magrolimab (priming) infusion will be 3 hours (±30 min) with dose of 1 mg/kg. 
For the subsequent doses, the magrolimab infusion will be 2 hours (±30 min) with dose of 30 
mg/kg. The reduced infusion time to 2 hours is utilized based on prior data demonstrating majority 
CD47 RO on peripheral blood cells, thus mitigating anticipated RBC toxicities from magrolimab.   
Magrolimab Premedication: oral acetaminophen 650 to 1000 mg and oral or IV 
diphenhydramine 25 to 50 mg or comparable regimen. If less than 4 hours has elapsed since a 
prior dose of acetaminophen has been given, the dose of acetaminophen premedication may be 
omitted. Premedication is required prior to the administration of the first 2 doses of magrolimab 
and in case of reintroduction with repriming. Premedication during subsequent infusions may be 
continued based on the treating physician’s clinical judgment and the presence/severity of prior 
IRRs. 
When magrolimab is given in combination with cetuximab, pembrolizumab, and/or docetaxel, 
magrolimab will be infused first. All patients should be monitored for 1 hour after infusion for 
priming, repriming, and maintenance doses during Cycle 1. Post infusion monitoring should begin 
after the infusion is complete but prior to administering any other study drug. Post infusion 
monitoring is not required for doses after Cycle 1 Day 15. Patients who experience any treatment-
emergent AEs during the observation period should be further monitored, as clinically appropriate. 
Patients may continue study treatment until they show evidence of disease progression, relapse, 
loss of clinical benefit, or unacceptable toxicity.  
 

 
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5.1.1.2 Magrolimab: Dose Modifications and Delays 
In most circumstances, the dose of magrolimab should not be reduced. Clinical safety and PK 
data from dose finding studies in both solid tumor and hematologic malignancies have not 
demonstrated any dose-dependent toxicities associated with magrolimab. 
Magrolimab should be withheld for any treatment-related Grade 4 adverse event, Grade 3 
hemolytic anemia that is medically significant (requiring hospitalization or prolongation of existing 
hospitalization, disabling, or limiting self-care activities of daily life) or unmanageable any-grade 
toxicity. Magrolimab may be reintroduced once the severity is Grade ≤2 or baseline. Depending 
on the duration of the dose hold, repriming may be required as outlined in Table 6 below.  If the 
investigator feels deviation from the above is needed, the PI should be consulted. Guidance on 
the management of anemia, infusion reactions and late hypersensitivity reactions, and 
pneumonitis are available in the Appendix. 
Criteria for permanent discontinuation of magrolimab include the following: 
• 
Grade 4 IRR 
• 
Grade 4 non-hematologic AE related to magrolimab that does not improve to Grade 2 or 
baseline within 30 days 
If magrolimab is discontinued for reasons other than disease progression, the remaining drug(s) 
in the combination regimen may be continued. Magrolimab may be withheld if treatment-emergent 
and/or magrolimab-related AEs occur, until clinical resolution or improvement per the treating 
physician. Treatment delays (not due to AEs) of more than 4 weeks (such as an unrelated medical 
condition with expected recovery) must be approved by the sponsor. 
The repriming guidelines shown in Table 6 should be followed for patients with dose delays. 
Magrolimab dosing and safety assessments should follow Cycle 1 and then subsequently switch 
back to the assigned cycle schedule. If repriming is necessary before the patient completes Cycle 
1 or Cycle 2, the repriming cycle is administered by repeating Cycle 1 dosing, followed by Cycle 
2 before proceeding to usual scheduling. 
 
Table 6. Repriming Guidelines for Magrolimab 
Dose 
Dosing Frequency 
Minimum Duration of Treatment 
Gap That Will Lead to Repriming 
1 mg/kg 
NA – used at initial priming 
2 weeks 
30mg/kg 
Weekly  
4 weeks 
Every 2 weeks 
4 weeks 
 
5.1.1.3 Magrolimab Dosing Guidance for Planned Surgical Procedures on Study 
If planned surgical procedures are needed for patients on study treatment, magrolimab will be 
delayed and restarted in accordance with table 7. 
 

 
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 Table 7. Magrolimab Dosing Guidance for Surgical Procedure 
Planned Surgical Procedure 
Magrolimab Dose Guidance 
Minimally invasive procedure 
(Examples: biopsies [excluding lung/liver], 
skin/subcutaneous lesion removal, 
cataract/glaucoma/ eye surgery/cystoscopy) 
Hold magrolimab dose 3 days prior to 
procedure and restart after 3 days 
Moderately invasive procedure 
(Examples: lung/liver biopsy, hysterectomy, 
cholecystectomy, hip/knee replacement, minor 
laparoscopic procedures, stent/angiopathy) 
Hold magrolimab dose 3 days prior to 
procedure and restart after 5 days 
Highly invasive procedure 
(Examples: central nervous system/spine surgery, 
major vascular surgery, cardiothoracic surgery, 
major laparoscopic surgery) 
Hold magrolimab dose 3 days prior to 
procedure and restart after 7 days 
 
 Cetuximab 
5.1.2.1 Packaging and Labeling 
Formulation: cetuximab is commercially sourced. Information regarding the formulation can be 
found in the current country-specific prescribing information. Cetuximab preparation, handling, 
and storage will be performed according to the approved label. 
Route of administration: intravenous (IV) infusion. 
Dose regimen: Cetuximab loading dose (400mg/m2) will be administered over 2 hours (± 10 min). 
Subsequent weekly cetuximab doses (250mg/m2) will be administered over 1 hour (± 10 min). 
Cetuximab 500 mg/m2 maintenance dose will be administered over 2 hours (± 10 min) . 
Patients may continue study treatment until they show evidence of disease progression, relapse, 
loss of clinical benefit, or unacceptable toxicity.  
5.1.2.2 Cetuximab: Dose Modifications and Delays 
Cetuximab is known to cause infusion reactions, dermatologic toxicities, and pulmonary toxicities. 
Dose reductions per key toxicities are described below (Table 8) and are in accordance with the 
cetuximab prescribing information. 
Table 8 Cetuximab Dose Modification and Toxicity Management Guidelines 
Adverse Reaction 
Severity (CTCAE v5.0) 
Dose Modification  
Infusion Reaction 
Grade 1 or 2 
Reduce the infusion rate by 50%. 
Grade 3 or 4 
Immediately and permanently, discontinue cetuximab. 
Dermatologic toxicities and 
infectious sequelae (e.g., 
acneiform 
rash, 
mucocutaneous disease) 
1st occurrence; Grade 3 or 4 
Delay infusion 1 to 2 weeks; if condition improves, 
continue at 250 mg/m2. If no improvement, discontinue 
cetuximab. 
2nd occurrence; Grade 3 or 
Delay infusion 1 to 2 weeks; if condition improves, 

 
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4 
continue at 200 mg/m2. If no improvement, discontinue 
cetuximab. 
3rd occurrence; Grade 3 or 4 
Delay infusion 1 to 2 weeks; if condition improves, 
continue at 150 mg/m2. If no improvement, discontinue 
cetuximab. 
4th occurrence; Grade 3 or 4 
Discontinue cetuximab. 
Pulmonary toxicity 
Acute onset or worsening 
pulmonary symptoms 
Delay infusion 1 to 2 weeks; if condition improves, 
continue at the dose that was being administered at 
the time of occurrence. If no improvement in 2 weeks 
or interstitial lung disease (ILD) is confirmed, 
discontinue ERBITUX. 
 
 Pembrolizumab  
5.1.3.1 Packaging and Labeling 
Formulation: pembrolizumab is commercially sourced. Information regarding the formulation can 
be found in the current country-specific prescribing information. Pembrolizumab preparation, 
handling, and storage will be performed according to the approved label. 
Route of administration: intravenous (IV) infusion. 
Dose regimen: Pembrolizumab will be administered at a dose of 200 mg using a 30-minute (±10 
minutes) IV infusion. 
Patients may continue study treatment until they show evidence of disease progression, relapse, 
loss of clinical benefit, or unacceptable toxicity.  
5.1.3.2 Pembrolizumab: Dose Modifications and Delays 
Adverse events associated with pembrolizumab exposure may represent an immune-based 
etiology. These immune-related AEs may occur shortly after the first dose or several months after 
the last dose of pembrolizumab treatment and may affect more than 1 body system 
simultaneously. Therefore, early recognition and initiation of treatment are critical to reduce 
complications. Based on existing clinical study data, most immune-related AEs were reversible 
and could be managed with interruptions of pembrolizumab, administration of corticosteroids, 
and/or other supportive care. For suspected immune-related AEs, ensure adequate evaluation to 
confirm etiology or exclude other causes. Additional procedures or tests such as bronchoscopy, 
endoscopy, and skin biopsy may be included as part of the evaluation. Based on the severity of 
immune-related AEs, withhold or permanently discontinue pembrolizumab and administer 
corticosteroids. Dose modification and toxicity management guidelines for immune-related AEs 
associated with pembrolizumab are provided in Table 9. If pembrolizumab is discontinued for 
reasons other than disease progression, the remaining drug(s) in the combination regimen may 
be continued. 
Table 9 Pembrolizumab Dose Modification and Toxicity Management Guidelines 

 
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Immune-
Related AE 
Toxicity Grade or 
Conditions 
(CTCAE 
Version 5.0) 
Action Taken 
with   
Pembrolizumab 
Immune-Related AE 
Management with 
Corticosteroid and/or 
Other Therapies 
Monitor and Follow-Up 
Pneumonitis 
Grade 2 
Withhold 
 Administer corticosteroids 
(initial dose of prednisone 
1-2 mg/kg or equivalent) 
followed by taper 
• Monitor patients for signs 
and symptoms of 
pneumonitis 
• Evaluate patients with 
suspected pneumonitis 
with radiographic imaging 
and initiate corticosteroid 
treatment 
• Add prophylactic 
antibiotics for opportunistic 
infections 
Grade 3 or 4 or 
recurrent Grade 2 
Permanently 
discontinue 
Diarrhea/colitis 
Grade 2 or 3 
Withhold 
 Administer corticosteroids 
(initial dose of prednisone 
1-2 mg/kg or equivalent) 
followed by taper 
• Monitor patients for signs 
and symptoms of 
enterocolitis (ie, diarrhea, 
abdominal pain, blood or 
mucus in stool with or without 
fever) and of bowel 
perforation (ie, peritoneal 
signs and ileus) 
• Patients with ≥ Grade 2 
diarrhea suspecting colitis 
should consider GI 
consultation and 
performing endoscopy to 
rule out colitis 
• Patients with diarrhea/colitis 
should be advised to drink 
liberal quantities of clear 
fluids. If sufficient oral fluid 
intake is not feasible, fluid 
and electrolytes should be 
substituted via IV infusion 
Grade 4 
Permanently 
discontinue 
AST/ALT 
elevation or 
increased 
bilirubin 
Grade 2 
Withhold 
 Administer corticosteroids 
(initial dose of prednisone 
0.5-1 mg/kg or equivalent) 
followed by taper 
• Monitor with liver function 
tests (consider weekly or more 
frequently until liver enzyme 
value returned to baseline or is 
stable) 
Grade 3 or 4 
Permanently 
discontinue 
 Administer corticosteroids 
(initial dose of prednisone 
1-2 mg/kg or equivalent) 
followed by taper 
T1DM or 
hyperglycemia 
Newly onset T1DM 
or Grade 3 or 4 
hyperglycemia 
associated with 
evidence of β-cell 
failure 
Withhold 
 Initiate insulin replacement 
therapy for patients with 
T1DM 
 Administer 
antihyperglycemic in 
patients with hyperglycemia 
• Monitor patients for 
hyperglycemia or other signs 
and symptoms of diabetes 

 
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Hypophysitis 
Grade 2 
Withhold 
Administer corticosteroids 
and initiate hormonal 
replacements as clinically 
indicated 
Monitor for signs and symptoms 
of hypophysitis (including 
hypopituitarism and adrenal 
insufficiency) 
Grade 3 or 4 
Withhold or 
permanently 
discontinuea 
Hyperthyroidism Grade 2 
Continue 
Treat with nonselective 
beta-blockers (eg, 
propranolol) or thionamides 
as appropriate 
Monitor for signs and symptoms 
of thyroid disorders 
Grade 3 or 4 
Withhold or 
permanently 
discontinuea 
Hypothyroidism Grades 2-4 
Continue 
Initiate thyroid replacement 
hormones (eg, 
levothyroxine or 
liothyronine) per standard of 
care 
Monitor for signs and symptoms 
of thyroid disorders 
Nephritis and 
renal 
dysfunction 
Grade 2 
Withhold 
Administer corticosteroids 
(prednisone 1-2 mg/kg or 
equivalent) followed by 
taper 
Monitor changes of renal 
function 
Grade 3 or 4 
Permanently 
discontinue 
Myocarditis 
Grade 1 or 2 
Withhold 
Based on severity of AE, 
administer corticosteroids 
Ensure adequate evaluation to 
confirm etiology and/or exclude 
other causes 
Grade 3 or 4 
Permanently 
discontinue 
All other 
immune- related 
AEs 
Intolerable/ 
persistent Grade 2 
Withhold 
Based on type and severity 
of AE, administer 
corticosteroids 
Ensure adequate evaluation to 
confirm etiology and/or exclude 
other causes 
Grade 3 
Withhold or 
discontinue based 
on the type of 
event. Events that 
require 
discontinuation 
include, and are 
not limited to, 
GBS and 
encephalitis. 
Grade 4 or 
recurrent Grade 3 
Permanently 
discontinue 
AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria 
for Adverse Events; GBS = Guillain-Barre Syndrome; GI = gastrointestinal; IV = intravenous; T1DM = type 1 diabetes mellitus 
aThe decision to withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician. 
For patients with Grade 3 or 4 immune-related endocrinopathy for which withholding of pembrolizumab is required, pembrolizumab 
may be resumed when the AE resolves to ≤ Grade 2 and is controlled with hormonal replacement therapy or achieves metabolic 
control. 
 
 
 Docetaxel  
5.1.4.1 Packaging and Labeling 
Formulation: Docetaxel is commercially sourced. Information regarding the formulation can be 
found in the current country-specific prescribing information. Docetaxel preparation, handling, and 
storage will be performed according to the approved label. 
Route of administration: intravenous (IV) infusion. 

 
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Dose regimen: docetaxel will be administered at a dose of 30mg/m2 using a 1 hour (±10 minutes) 
IV infusion, every week, for 2 – 4 cycles (1 cycle = 21 days).  
Premedication and Prophylaxis: For docetaxel treatment, patients can be premedicated with 
oral corticosteroids such as dexamethasone 4 mg twice daily for 3 days starting 1 day prior to 
docetaxel administration to reduce the incidence and severity of fluid retention and the severity of 
hypersensitivity reactions. 
5.1.4.2 Docetaxel: Dose Modifications 
Docetaxel is known to cause neutropenia, hepatotoxicity, peripheral neuropathy, fluid retention, 
and hypersensitivity reactions. Dose reductions per key toxicities are described below and are in 
accordance with the docetaxel prescribing information. Of note, coadministration of a strong 
CYP3A4 inhibitor should be avoided; docetaxel dose should be reduced by 50% if a strong 
CYP3A4 inhibitors cannot be avoided. 
 
a. Neutropenia 
Docetaxel causes neutropenia; guidance on dose reductions is shown in Table 10. Patients 
should have an absolute neutrophil count ≥ 1500 cells/μL before initiating the next cycle of 
docetaxel therapy. Myeloid growth factor support is allowed per institutional guidelines 
Table 10: Docetaxel Dose Modification Guidelines for Neutropenia 
Hematologic Toxicity 
Occurrence 
Weekly Docetaxel Dose (mg/m2) 
Neutropenic fever (nadir ANC < 
500 cells/µL with fever > 38°C) for 
> 7 days despite growth factor 
support 
Delay of next cycle by > 14 days 
for nadir ANC < 1500 cells/μL 
or 
Nadir ANC < 500 cells/µL for > 7 
days 
First 
25 
Second 
20 
 
Third 
 
Discontinue treatment 
ANC = absolute neutrophil count 
 
b. Hepatic Toxicity  
Docetaxel may be withheld for Grade 3 or 4 hepatic toxicity deemed related to docetaxel as 
specified in Table 11. In addition, the investigator should make every effort to exclude 
malignant disease progression as a cause of liver enzyme derangement, which would not 
be considered a toxicity for docetaxel. 
 
Table 11: Docetaxel Dose Modification Guidelines for Hepatic Toxicity 
Hepatic Toxicity 
Occurrence 
Docetaxel Dose Modification 

 
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AST or ALT > 1.5 x ULN (or baseline if 
higher) and alkaline phosphatase 
> 2.5 x ULN 
or 
Bilirubin > 1.25 x ULN 
First 
Interrupt treatment until AST/ALT ≤ 1.5 
x ULN and alkaline phosphatase ≤ 2.5 x 
ULN, then reduce to 25 mg/m2 
Interrupt treatment until bilirubin ≤ 1.25 x 
ULN, then reduce to 25 mg/m2 
If toxicity does not resolve to above 
criteria within 3 weeks, discontinue 
treatment 
Second 
Interrupt treatment until AST/ALT ≤ 1.5 x 
ULN and 
alkaline phosphatase ≤ 2.5 x ULN, then 
reduce to 
20 mg/m2 
Interrupt treatment until bilirubin ≤ 1.25 x 
ULN, then reduce to 20 mg/m2 
If toxicity does not resolve to above 
criteria within 3 weeks, discontinue 
treatment 
Third 
Discontinue treatment 
AST or ALT > 3 x ULN (or baseline if 
higher) 
and 
Bilirubin > 2 x ULN 
Any 
Discontinue treatment 
Bilirubin > 5 x ULN 
Any 
Discontinue treatment 
AST or ALT > 5 to 10 x ULN for 
> 2 weeks 
or 
AST or ALT > 10 x ULN or baseline 
Any 
Discontinue treatment 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal 
 
c. Peripheral Neuropathy 
Patients who develop ≥ Grade 3 peripheral neuropathy related to docetaxel should have 
docetaxel discontinued permanently. 
d. Other Toxicities 
Docetaxel dose modifications for other Grade 3 or 4 hematologic or nonhematologic 
toxicities deemed related to docetaxel are shown in Table 12. Docetaxel should be delayed 
until improvement of the Grade 3 or 4 toxicity to at least Grade 2 or baseline. 
Table 12: Docetaxel other toxicities management 
Other Toxicity 
Occurrence 
Weekly Docetaxel Dose (mg/m2) 
Grade 3 or 4 nonhematologic or 
hematologic toxicitya that does not 
resolve to ≤ Grade 2 within 14 days 
First 
Delay 25 
Second 
20 
Third 
Discontinue treatment 
a Grade 3 or 4 nonhematologic or hematologic toxicities apply to those not described in the above dose modification 
sections 

 
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32 
 
 Preparation/Handling/Storage/Accountability 
Docetaxel, Cetuximab and Pembrolizumab are commercially sourced. Their preparation, 
handling, and storage will be performed according to the approved label. The IMP magrolimab 
will be supplied for the study by Gilead. Preparation and administration of magrolimab are detailed 
in the pharmacy manual. Magrolimab will be shipped to MD Anderson Cancer Center (MDACC) 
with a Drug Shipment and Proof of Receipt form. A drug accountability log will be maintained. The 
information contained on the log should be sufficient to comply with applicable good clinical 
practice (GCP) regulations. At the time of study closure, both the unused, used, and expired study 
drug will be destroyed by MD Anderson’s Investigational Pharmacy Services per MD Anderson’s 
institutional standard operating procedure (SOP). 
 
 IND Agent(S)/IDE Device(s) 
Please refer to Section 5.1 “Agent Administration”. 
 Other Modality(ties) or Procedures 
N/A 
 
 Dose Expansion Cohorts 
N/A 
 
 General Concomitant Medication and Supportive Care Guidelines 
 
 Allowed Medications 
All treatments that the investigator considers necessary for the subject’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care. A single dexamethasone dose of up to 12 mg can be administered prior to exam 
under anesthesia/biopsy as per investigator discretion. A brief course of systemic glucocorticoids 
(≤7 days) is also allowed for contrast-dye allergy. 
All concomitant medications received within 28 days before the first dose of trial 
treatment through the EOT visit will be recorded in the electronic medical record 
(EMR). 
 Prohibited Concomitant Medication 
The subject is prohibited from receiving the following therapies during the Screening and 
Treatment periods of this study: 
• 
Exposure to any investigational drug within 4 weeks or 5 half-lives whichever is longer or 
concurrently with IP administration. 
• 
Chronic immunosuppressive medications including, but not limited to systemic corticosteroids 
at doses exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and 

 
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TNF-α blockers. Use of immunosuppressive medications for the management of 
investigational product-related AEs or in subjects with contrast allergies is acceptable. In 
addition, use of inhaled and intranasal corticosteroids is permitted. 
• 
Live attenuated vaccines within 30 days of IMP dosing (i.e., 30 days prior to the first dose).  
Inactivated vaccines, such as the injectable influenza vaccine, are permitted. 
• 
Coadministration of docetaxel and a strong CYP3A4 inhibitor should be avoided; 
if a strong CYP3A4 inhibitors cannot be avoided, docetaxel dose should be 
reduced by 50% as stated in section 5.1.4.2 
 
 
 Duration of Therapy 
In the absence of treatment delays due to adverse event(s), treatment may continue for 2 years 
(~104 weeks) or until one of the following criteria applies: 
- 
Disease progression by RECIST v1.1 
- 
Unacceptable toxicity 
- 
Loss of clinical benefit 
- 
Clinically significant change in the patient’s status that precludes further treatment (eg, 
pregnancy or other AEs) 
- 
Patient request, with or without a stated reason 
- 
Patient noncompliance 
- 
Discontinuation of the study at the request of Gilead, a regulatory agency, or an 
institutional review board (IRB) or independent ethics committee (IEC) 
- 
Investigator or treating physician decision in the absence of any of the above 
Although progression of disease (PD) is considered a sufficient reason for discontinuing a patient 
from study treatment, given that delayed treatment benefit can be seen with immunotherapies, 
the investigator is allowed to continue to treat the patient beyond progression until confirmation 
of disease progression through a subsequent assessment at least 4 weeks apart (ie, disease 
worsening compared to the previous assessment) with the option of continuing treatment while 
awaiting radiologic confirmation of PD. If repeat imaging shows a reduction in the tumor burden 
compared to the initial scan demonstrating PD, treatment may be continued as per treatment 
calendar. If repeat imaging confirms PD, subjects will be discontinued from study therapy. In 
determining whether or not the tumor burden has increased or decreased, investigators should 
consider all target lesions as well as non-target lesions. The decision to continue study treatment 
after the first evidence of PD is at the Investigator’s discretion based on the clinical status of the 
subject. Subjects may receive study treatment while waiting for confirmation of PD if they are 
clinically stable as defined by the following criteria:  
- 
Absence of signs and symptoms (including worsening of laboratory values) indicating 
disease progression  
- 
No decline in ECOG PS  
- 
Absence of rapid progression of disease  

 
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- 
Absence of progressive tumor at critical anatomical sites (e.g., cord compression) 
requiring urgent alternative medical intervention 
Patients discontinued from treatment should still comply with the End of Study visit. 
The reason(s) for protocol therapy discontinuation, the reason(s) for study removal, and the 
corresponding dates must be documented in the Case Report Form (CRF). 
 Duration of Follow-up 
All patients will be followed for survival until death, withdraw from consent, lost to follow-up, or the 
end of study, whichever occurs first. 
 
 Dosing Delays/Dose Modifications 
Please refer to Section 5.1 “Agent Administration”. 
 
6 
STUDY ASSESSMENTS AND PROCEDURES   
The study procedures to be conducted for each patient enrolled in the study are presented in 
tabular form in Table 1 and Table 2.  
The investigator must document any deviation from the protocol procedures and notify the IRB 
and the sponsor. 
 
 Schedule of Activities (SoA) 
 
 

 
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 COHORT A: Anti-PD1 naïve, treatment with magrolimab, cetuximab and 
pembrolizumab 
Table 1. Study Assessment Cohort A 
Proceduresa 
 Screening 
Cycle (21-Day Cycles) 
 
1 
2 
3 
(…) 34 
EOTm 
Cycle Day (Visit 
window) 
Days  
-28 to -1  
D1 
D2  
D8 (±2d) 
D15 (±2d) 
D1 (±2d) 
D8 (±2d) 
D15 (±2d) 
D1 (±2d) 
D8 (±2d) 
D15 (±2d) 
D1 (±2d) 
D8 (±2d) 
D15 (±2d) 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical history 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Elegibility 
Verification 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Concurrent meds 
 
X ---------------------------------------------------------------  X 
  
Physical examb 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Vital signsc  
X 
X 
 X 
X  
X  
X 
X  
X  
X 
X  
X 
X 
X  
X  
X 
Weight 
X 
X 
  
  
 
X 
 
  
X 
 
  
X 
  
  
X 
Height 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Performance Status 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Tumor sampled 
X 
  
  
  
  
  
  
  
 
  
  
  
  
  
  
Adverse Events 
 
X ---------------------------------------------------------------  X 
X 
Magrolimab 
  
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Cetuximab 
  
  
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Pembrolizumabe 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
  
CBC w/diff, 
chemistryf 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Blood Type and Cross 
Match 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation 
parametersg 
X 
 
  
  
  
 
  
  
 
  
  
 
  
  
 
Serum pregnancy testh 
X 
  
  
  
  
  
  
  
 X 
  
  
  
  
  
  
Thyroid functioni 
X 
  
  
  
  
  
  
  
X  
  
  
  
  
  
X 
EKGj 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Imagingk 
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
Hb/Htn 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood for biomarkersl 
  
X 
  
  
  
X 
  
  
X 
  
  
 
  
  
 
Viral Panelo 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a All procedures (X) to be performed pre-infusion unless stated otherwise. 
b Full physical examination at baseline; targeted physical examination at other time points. 
c Vital signs include temperature, blood pressure, pulse, and respiratory rate. 
d Baseline tumor biopsy is mandatory with two exceptions: 1) the patient recently underwent tumor biopsy and have a 
minimum of 1 block and/or 20 unstained slides available for future correlative analysis; in this case, the tumor biopsy 
is strongly encouraged but not mandatory; 2) the patient underwent a tumor biopsy prior to signing consent and 

 
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36 
adequate tissue was banked by another MDACC tissue collection protocol (Eg: lab02-039) and the tissue can be 
transferred for use in this protocol; in this case, a biopsy can be waived. Additionally, a tumor biopsy will be strongly 
encouraged but optional at progression.    
e Pembrolizumab can be administered at 400 mg Q6W, if a Q2W schedule is entertained for magrolimab and 
cetuximab.  
f CBC w/diff include CBC with hemoglobin, WBC with differential, and platelet count. Chemistry include sodium, 
potassium, chloride, magnesium, glucose, creatinine, blood urea nitrogen (BUN), ALT, AST, total bilirubin, and alkaline 
phosphatase (ALP). CBC needs to be completed within 24 hours prior to C1D1, chemistry can be done within 7 days 
of C1D1. 
g Coagulation tests: prothrombin time, PTT and INR performed at Screening and as clinically indicated. 
h Pre-menopausal female subjects of childbearing potential only. Pregnancy test should be done within 14 days of 
starting therapy during screening and every 6 weeks (+/- 14 days) during trial therapy 
i Thyroid function will consist of TSH and free T4; Thyroid function will be repeated every 2 cycles. 
j Electrocardiogram during screening, thereafter as clinically indicated. 
k Imaging will be performed at baseline and every 6 weeks ± 1 week. 
l Blood for correlative studies will be collected at baseline and prior to cycle 3 day 1 (C3D1). Additional blood samples 
will be collected on C2D1, and at the time of progression. The following samples will be collected for future biomarker 
analysis: EDTA Vacutainer® (checkpoint markers/CAFs): 10 mL = 1 x 10 mL; Streck Cell Free-DNA BCT (ctDNA): 20 
mL = 2x 10 mL; and Sodium Heparin (immunoprofiling): 40 ml = 4 x 10 mL. Missed research blood collection will not 
constitute a protocol violation.  
m EOT=End of treatment. The EOT Visit will occur with disease progression, unacceptable side effects, or after 2 years 
of systemic therapy at least 90 days after the last dose of study therapy for Cohort A and at least 30 days after the last 
dose of study therapy for Cohort B. After the EOT evaluation, information on additional oncologic treatment, time to 
disease progression/recurrence, sites of recurrence, additional therapies, long-term survival, and other relevant clinical 
data may be obtained. Patients (or their family members or designees) may be contacted by telephone or in writing or 
by electronic mail or during clinic visits after treatment discontinuation for collection of long-term follow-up data. Long-
term follow-up clinical information may also be obtained through chart reviews. 
n Hb and hematocrit must be checked 3 to 6 hours after the initiation of the first and second doses of magrolimab 
o HIV, hepatitis B and/or hepatitis C viral load will be required at Screening only for patients with known history of 
HIV, hepatitis B, and/or hepatitis C 
 
 

 
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 COHORT B: Anti-PD1 refractory, treatment with magrolimab, cetuximab and 
docetaxel 
 
Table 2: Study Assessment Cohort B 
Proceduresa 
Screening 
Cycle (21-Day Cycles) 
Cycle 
1 
2 
3 
(…) 34 
EOTm 
Cycle Day (Visit window) 
Days  
-28 to -1  
D1  
D2  
D8 (±2d) 
D15 (±2d) 
D1 (±2d) 
D8 (±2d) 
D15 (±2d) 
D1 (±2d) 
D8 (±2d) 
D15 (±2d) 
D1 (±2d) 
D8 (±2d) 
D15 (±2d) 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical history 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Elegibility Verification 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Concurrent meds 
 
X ---------------------------------------------------------------  X 
  
Physical examb 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Vital signsc  
X 
X 
X  
 X 
X  
X 
X  
X  
X 
X  
X  
X 
X  
X  
X 
Weight 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Height 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Perfomance Status 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Tumor sampled 
X 
  
  
  
  
  
  
  
 
  
  
 
  
  
  
Adverse Events 
 
X ---------------------------------------------------------------  X 
X 
Magrolimab 
  
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Cetuximab 
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Docetaxele 
  
  
 
 
 
X 
X 
X 
X 
X 
X 
  
  
  
  
CBC w/diff, chemistryf 
X 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Blood Type and Cross 
Match 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation parametersg 
X 
  
  
  
  
 
  
  
 
  
  
 
  
  
 
Serum pregnancy testh 
X 
  
  
  
  
  
  
  
X  
  
  
  
  
  
  
Thyroid functioni 
X 
  
  
  
  
  
  
  
X  
  
  
  
  
  
X  
EKGj 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Imagingk 
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
Hb/Htn 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood for biomarkersl 
  
X 
  
  
  
X 
  
  
X 
  
  
 
  
  
 
a All procedures (X) to be performed pre-infusion unless stated otherwise. 
b Full physical examination at baseline; targeted physical examination at other time points. 
c Vital signs include temperature, blood pressure, pulse, and respiratory rate. 
d Baseline tumor biopsy is mandatory with two exceptions: 1) the patient recently underwent tumor biopsy and have a 
minimum of 1 block and/or 20 unstained slides available for future correlative analysis; in this case, the tumor biopsy 
is strongly encouraged but not mandatory; 2) the patient underwent a tumor biopsy prior to signing consent and 
adequate tissue was banked by another MDACC tissue collection protocol (Eg: lab02-039) and the tissue can be 
transferred for use in this protocol; in this case, a biopsy can be waived. Additionally, a tumor biopsy will be strongly 
encouraged but optional at progression.      

 
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e Docetaxel will be administered only for 2 to 4 cycles. 
f CBC w/diff include CBC with hemoglobin, WBC with differential, and platelet count. Chemistry include sodium, 
potassium, chloride, magnesium, glucose, creatinine, blood urea nitrogen (BUN), ALT, AST, total bilirubin, and alkaline 
phosphatase (ALP). CBC needs to be completed within 24 hours prior to C1D1, chemistry can be done within 7 days 
of C1D1. 
g Coagulation tests: prothrombin time, PTT and INR performed at Screening and as clinically indicated. 
h Pre-menopausal female subjects of childbearing potential only. Pregnancy test should be done within 14 days of 
starting therapy during screening and every 6 weeks (+/- 14 days) during trial therapy 
i Thyroid function will consist of TSH and free T4; Thyroid function will be repeated every 2 cycles. 
j Electrocardiogram during screening, thereafter as clinically indicated. 
k Imaging will be performed at baseline and every 6 weeks ± 1 week. 
l Blood for correlative studies will be collected at baseline and prior to cycle 3 day 1 (C3D1). Additional blood samples 
will be collected on C2D1, and at the time of progression. The following samples will be collected for future biomarker 
analysis: EDTA Vacutainer® (checkpoint markers/CAFs): 10 mL = 1 x 10 mL; Streck Cell Free-DNA BCT (ctDNA): 20 
mL = 2x 10 mL; and Sodium Heparin (immunoprofiling): 40 ml = 4 x 10 mL. Missed research blood collection will not 
constitute a protocol violation.   
m EOT=End of treatment. The EOT Visit will occur with disease progression, unacceptable side effects, or after 2 years 
of systemic therapy at least 90 days after the last dose of study therapy for Cohort A and at least 30 days after the last 
dose of study therapy for Cohort B. After the EOT evaluation, information on additional oncologic treatment, time to 
disease progression/recurrence, sites of recurrence, additional therapies, long-term survival, and other relevant clinical 
data may be obtained. Patients (or their family members or designees) may be contacted by telephone or in writing or 
by electronic mail or during clinic visits after treatment discontinuation for collection of long-term follow-up data. Long-
term follow-up clinical information may also be obtained through chart reviews. 
n Hb and hematocrit must be checked 3 to 6 hours after the initiation of the first and second doses of magrolimab 
 
 Screening phase 
All subjects must first read, understand, and sign the institutional review board approved informed 
consent before any study-specific screening procedures are performed. After signing the informed 
consent, completing all screening procedures, and being deemed eligible for entry, subjects will 
be enrolled in the study using the institutional database (CORe). Procedures that are performed 
prior to the signing of the informed consent and are considered standard of care may be used as 
screening assessments if they fall within the 28-day screening window. That includes screening 
physical examination, hematology, blood chemistry and radiologic imaging. A biopsy will be 
mandatory during Screening, unless 1) the patient recently underwent tumor biopsy and have a 
minimum of 1 block and/or 20 unstained slides available for future correlative analysis; in this 
case, the tumor biopsy is strongly encouraged but not mandatory; 2) the patient underwent a 
tumor biopsy prior to signing consent and adequate tissue was banked by another MDACC tissue 
collection protocol and the tissue can be transferred for use in this protocol; in this case, a biopsy 
can be waived. Tumor PD-L1 CPS must be documented in the EMR. Tissue will be banked for 
biomarker analysis. 
 
 Adverse Events  
At each visit, all AEs observed by the investigator or reported by the patient that occur from the 
first day of administration of the investigational agent (C1D1) through 30 days after the last dose 
of study treatment are to be reported using the applicable electronic case report form (eCRF). Full 
details on the definitions, assessment, and reporting instructions for AEs are provided in Section 
10. 

 
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 Biomarker Assessments 
Biospecimen samples will be collected to assess treatment response biomarkers and to define 
correlates of clinical efficacy and/or safety, as outlined in Section 2.3. The biomarker sample 
collection schedules are outlined in Table 1 and Table 2. 
Patients are required to submit mandatory pretreatment tumor tissue from a core needle or 
excisional tumor biopsy (fine needle aspirate is not adequate). A newly obtained biopsy collected 
within 90 days prior to study treatment start is strongly preferred, but an archival sample is 
acceptable. 
The correlative analysis includes but are not limited to efficacy according to baseline tumor PD-
L1 CPS and mutational profile. 
For additional details and instructions regarding tissue requirements and procedures for sample 
collection, storage, and shipment, refer to the Study Laboratory Manual. 
 Biospecimen repository 
As part of the study, a tissue and blood sample repository will be created. The objective of this 
biospecimen sample repository will be to provide material for future evaluations of other relevant 
biomarkers that may be associated with clinical outcomes. Some of the de-identified tissue, blood, 
and oral rinse samples might be transferred to outside vendors for biomarker analysis. A written 
informed consent will be obtained from patients enrolled in this study so that these remaining 
samples may be analyzed in the future for biomarkers. Samples will be banked at MDACC. If a 
subject withdraws consent to the use of donated samples, the samples will be disposed 
of/destroyed, and the action documented. 
 Safety Assessments 
Safety will be assessed at every clinical visit and in an ongoing basis throughout the study from 
the first day of administration of the investigational agent (Cycle 1 Day 1) through 30 days after 
the last dose of study treatment. All patients who receive at least one dose of the investigational 
agent will be included in the safety analysis. Adverse events (AEs) will be graded using NCI-
CTCAE version 5. Frequency of AEs, serious AEs, discontinuation of study drug due to AEs and 
changes from baseline laboratory parameter values will be evaluated.   
 End of Treatment (EOT) Visit 
In order to ensure more adequate capture of immune-related adverse events, the EOT visit for an 
individual patient will occur at least 90 days after the last dose of study therapy for Cohort A. For 
Cohort B, the EOT visit will occur at least 30 days after the last dose of study therapy. 
 Long-term follow-up 
After the End of Treatment evaluation, information on additional oncologic treatment, time to 
disease progression/recurrence, sites of recurrence, additional therapy for recurrence, long-term 
survival, and other relevant clinical data may be obtained. Patients (or their family members or 
designees) may be contacted by telephone or in writing or by electronic mail or during clinic visits 

 
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after treatment discontinuation for collection of long-term follow-up data. Long-term follow-up 
clinical information may also be obtained through chart reviews. 
 End of Study 
For All Patients: The end of the entire study for all patients is defined as the date on which the 
last patient remaining on study completes the last study visit/call or when the sponsor decides to 
end the study. The sponsor reserves the right to terminate the study at any time for any reason 
(including safety). 
For Individual Patients: Patients are considered to have completed study participation altogether 
when they are no longer followed for survival.  
All patients will be followed for survival until death, withdraw from consent, lost to follow-up, or the 
end of study, whichever occurs first. 
For any patient who dies during this follow-up period, the immediate cause of death must be 
reported to the sponsor. 
 
7 
ADVERSE EVENT, SERIOUS ADVERSE EVENT (SAE)  
Investigators will assess the occurrence of adverse events (AE) and serious adverse events 
(SAE) at all subject evaluation time points during the study as per Schedule of Assessments. 
Assessments will consist of monitoring and recording of AEs and serious AEs, physical 
examination, measurement of protocol-specific laboratory variables and vital signs, as well as 
other tests deemed important for this protocol. Circumstances in which these assessments should 
be reported as AEs are described below. AE’s will be collected, graded, attribution assigned on 
AE logs that will be available in the EMR and entered on Case Report Form (CRF) in the DMI 
database. The AE duration (i.e., start and end dates) and action taken will also be recorded. 
Gilead will receive a copy of the investigational new drug (IND) office eSAE form. All patients who 
have received at least one exposure to study drug will be evaluated for safety of the study drug. 
 
 Definition of Adverse Events (AE) 
An AE is defined as any untoward medical occurrence in a patient regardless of its causal 
relationship to study treatment. An AE can be any unfavorable and unintended sign (including any 
clinically significant abnormal laboratory test result), symptom, or disease temporally associated 
with the use of the study treatment, whether or not it is considered to be study drug(s) related. 
Included in this definition are any newly occurring events and any previous condition that has 
increased in severity or frequency since the administration of study 
All AEs that are observed by the Investigator, staff or mentioned by the subject either 
spontaneously or upon questioning will be recorded in the AE log and entered in the study 
database. 
The following are NOT considered AEs: 
- 
Pre-existing condition: A pre-existing condition (documented on the medical history) is not 

 
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considered an AE unless the severity, frequency, or character of the event worsens during 
the study period. 
- 
Pre-planned or elective hospitalization: A planned hospitalization (Eg: surgery) is not 
considered an SAE, but rather a therapeutic intervention. However, if during the pre-
planned hospitalization an event occurs, which prolongs the hospitalization or meets any 
other SAE criteria, the event will be considered an SAE. Surgeries or interventions that were 
under consideration, but not performed before enrollment in the study, will not be 
considered serious if they are performed after enrollment in the study for a condition that 
has not changed from its baseline level. Elective hospitalizations for social reasons, solely 
for the administration of investigational agent, or due to long travel distances are also not 
SAEs. 
- 
Diagnostic Testing and Procedures: Testing and procedures should not to be reported as 
AEs or SAEs, but rather the cause for the test or procedure should be reported. 
- 
Any adverse event clearly attributable to disease progression 
The causality of AEs (their relationship to all study treatment/procedures) will be assessed by 
the investigator(s) and attributions will be made as per below: 
- 
Attribution - the determination of whether an adverse event is related to a medical 
treatment or procedure.  
- 
Definite - the adverse event is clearly related to the investigational agent(s). 
- 
Probable - the adverse event is likely related to the investigational agent(s). 
- 
Possible - the adverse event may be related to the investigational agent(s). 
- 
Unlikely - the adverse event is doubtfully related to the investigational agent(s). 
- 
Unrelated - the adverse event is clearly NOT related to the investigational agent(s). 
The severity of the adverse events (AEs) will be graded according to the U.S. Department of 
Health and Human Services, National Institutes of Health, National Cancer Institute, Common 
Terminology Criteria for Adverse Events (CTCAE), Version 5.0.  
Events not included in the NCI CTCAE will be scored as follows: 
• 
Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required 
beyond prophylaxis. 
• 
Grade 2: Moderate: discomfort present with some disruption of daily activity, require 
treatment. 
• 
Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line 
treatment.  
• 
Grade 4: Life Threatening: discomfort that represents immediate risk of death 
• 
Grade 5: Death 
The investigator (or physician designee) is responsible for verifying and providing source 
documentation for all adverse events, assigning the attribution and assessing the severity of the 
AE, the causal relationship between any events and the clinical study procedure, activities or 
device.  Additionally, the Investigator is responsible for providing appropriate treatment for the 

 
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event and for adequately following the event until resolution for all adverse events for subjects 
enrolled. 
  
 Adverse Event of Special Interest (AESI) 
An adverse event of special interest is an AE (serious or nonserious) of scientific and medical 
concern specific to the Sponsor’s product or program, for which ongoing monitoring and 
immediate notification by the Investigator to the Sponsor is required. Such events may require 
further investigation in order to characterize and understand them. Adverse events of special 
interest may be added, modified or removed during a study by protocol amendment. The 
following events need to be reported as AESIs: 
• Pregnancy of a female participant entered in a study as well as pregnancy occurring in a female 
partner of a male participant entered in a study with IMP/NIMP; 
- Pregnancy occurring in a female participant entered in the clinical trial or in a female partner 
of a male participant entered in the clinical trial.  
- In the event of pregnancy in a female participant, IMP should be discontinued. 
- Follow-up of the pregnancy in a female participant or in a female partner of a male participant 
is mandatory until the outcome has been determined. 
• Symptomatic overdose (serious or nonserious) with IMP/NIMP 
- An overdose of IMP is defined as: increase of at least 30% of the dose to be administered in 
the specified duration or if the dose is administered in less than half the recommended 
duration of administration. 
- An overdose (accidental or intentional) with the NIMP is an event suspected by the 
Investigator or spontaneously notified by the participant (not based on systematic pills count) 
and defined as at least twice the intended dose within the intended therapeutic interval, 
adjusted according to the tested drug. 
• An elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value 
that is greater than or equal to 3 times the ULN and an elevated total bilirubin lab value that is 
greater than or equal to 2 times the ULN and, at the same time, an alkaline phosphatase lab 
value that is less than 2 times the ULN, as determined by way of protocol specified laboratory 
testing or unscheduled laboratory testing*. 
*Note: These criteria are based upon available regulatory guidance documents. The purpose of 
the criteria is to specify a threshold of abnormal hepatic tests that may require an additional 
evaluation for an underlying etiology. The trial site guidance for assessment and follow up of 
these criteria can be made available. It may also be appropriate to conduct additional evaluation 
for an underlying etiology in the setting of abnormalities of liver blood tests including AST, ALT, 
bilirubin, and alkaline phosphatase that do not meet the criteria noted above. In these cases, the 
decision to proceed with additional evaluation will be made through consultation between the 
study investigators and the Sponsor. 

 
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• Other project-specific AESIs 
- infusion-related reaction Grade ≥2 
- Cytokine Release Syndrome Grade ≥2 
- Immune effector cell associated neurotoxicity of any grade 
- Vascular leak syndrome of any grade 
- Any immune-related AE Grade ≥3 
- Arrhythmia Grade ≥3 
 
 Unexpected Adverse Events 
An “unexpected” AE is an AE that is not listed in the Investigator's Brochure/package insert or is 
not listed at the specificity or severity that has been observed. "Unexpected" also refers to AEs 
that are mentioned in the Investigator's Brochure as occurring with a class of drugs or as 
anticipated from the pharmacological properties of the drug, but are not specifically mentioned 
as occurring with the study drug under investigation. 
 
Adverse Events or Adverse Device Effects will be captured according to protocol phase 
I recording guidelines: 
 
Recommended Adverse Event Recording Guidelines 
Attribution 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Unrelated 
Phase I 
Phase I 
Phase I 
Phase II 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Unlikely 
Phase I 
Phase I 
Phase I 
Phase II 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Possible 
Phase I 
Phase II 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Probable 
Phase I 
Phase II 
 Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Definitive 
Phase I 
Phase II 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
Phase I 
Phase II 
Phase III 
 
7.4 

 
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Serious Adverse Event (SAE) Reporting Requirements for MD Anderson Sponsored IND 
Protocols 
  
An adverse event or suspected adverse reaction is considered “serious” if, in the view of 
either the investigator or the sponsor, it results in any of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse 
(21 CFR 312.32). 
  
• 
Important medical events as defined above, may also be considered serious adverse 
events. Any important medical event can and should be reported as an SAE if deemed 
appropriate by the Principal Investigator or the IND Sponsor, IND Office. 
  
• 
All events occurring during the conduct of a protocol and meeting the definition of a SAE 
must be reported to the applicable Institutional Review Board (IRB) of record in 
accordance with their timeframes and procedures. 
• 
Serious adverse events will be captured from the time of the first protocol-specific 
intervention, until 30 days after the last dose of study drug, unless the participant 
withdraws consent. 
• 
Serious adverse events must be followed until clinical recovery is complete and laboratory 
tests have returned to baseline, progression of the event has stabilized, or there has been 
acceptable resolution of the event. 
 
• 
All SAEs, expected or unexpected/ initial or follow up, including the development of new 
malignancies, must be reported to the IND Office within 5 working days of knowledge of 
the event regardless of the attribution. 
  
• 
Death or life-threatening events that are unexpected, possibly, probably or definitely 
related to the study drug must be reported (initial or follow up) to the IND Office within 24 
hours of knowledge of the event. 
  
• 
Additionally, any serious adverse events that occur after the 30 day time period, that are 
related to the study treatment must be reported to the IND Office. This may include the 
development of new malignancies. 
  
• 
The electronic SAE application (eSAE) will be utilized for safety reporting to the IND Office. 
  
• 
All events reported to the supporting company must also be reported to the IND Office. 
Reporting to FDA: 

 
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• 
Serious adverse events will be forwarded to FDA by the IND Sponsor according to 
21 CFR 312.32. 
  
It is the responsibility of the PI and the research team to ensure serious adverse events 
are reported according to the Code of Federal Regulations, Good Clinical Practices, the 
protocol guidelines, the sponsor’s guidelines, and Institutional Review Board policy. 
 
 
 Investigator Communication with Supporting Companies 
The investigator and research team will inform Gilead of any SAE or AESI as assessed by the 
PI and will forward all IND Office eSAE reports to Gilead according to the IND Office reporting 
requirement timelines (Section 7.4). A cover page will accompany the form indicating: 
a. Notification from an Investigator Sponsored Study 
b. The Investigator IND number assigned by the FDA 
c. The Investigator’s name and address 
 
If it is not possible to record and transmit the SAE information electronically, the SAE will be 
reported on the paper SAE reporting form and transmitted by Fax. 
The reportable will be timely submitted to Gilead’s Central Safety Mailbox or Fax. All events 
submitted to the supporting company should also be sent to the IND Sponsor. 
Email: Safety_FC@gilead.com 
Fax: 1-650-522-5477 
 
 
 Adverse Event Reporting Period 
All AEs whether serious or non-serious, will be captured from the time of the first administration 
of the investigational agent until 30 days following the last dose of study drug or until the 
initiation of alternative anticancer therapy. Progressive disease should NOT be reported as an 
event term, but instead symptoms/clinical signs of disease progression may be reported. 
All Grade 3 – 5 adverse events, regardless of seriousness, severity, or presumed relationship 
to study drug, must be recorded using medical terminology in the source document. All records 
will need to capture the details of the duration and the severity of each episode, the action taken 
with respect to the study drug, investigator’s evaluation of its relationship to the study drug, and 
the event outcome. Whenever possible, diagnoses should be given when signs and symptoms 
are due to a common etiology (e.g., cough, runny nose, sneezing, sore throat, and head 
congestion should be reported as "upper respiratory infection"). 
All deaths should be reported with the primary cause of death as the AE term, as death is typically 
the outcome of the event, not the event itself. 
 

 
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 Other events requiring reporting  
 Overdose 
Any overdose of IMP should be recorded in the medical records (including quantity of the excess 
dose and the duration of the overdose). An overdose will not be considered an SAE unless the 
outcome of the overdose meets seriousness criteria. If overdose occurs, symptomatic 
management is indicated.  
In the event of an overdose, the investigator should: 
1. Contact the Sponsor (IND office) within 24 hours of knowledge 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
intervention can no longer be detected systemically (at least 30 days). 
3. Document appropriately in the e-CRF. 
 
 Pregnancy 
Before study enrollment, subjects must agree to take appropriate measures to avoid pregnancy. 
However, should a pregnancy occur, consent to provide follow-up information regarding the 
outcome of the pregnancy and the health of the infant until 30 days  old will be requested. 
A female subject must immediately inform the Investigator if she becomes pregnant from the time 
of consent to 6 months after the last dose of study combination. A male subject must immediately 
inform the Investigator if his partner becomes pregnant from the time of consent to 3 months after 
the last dose of study drug. Any female subjects receiving study drug(s) who become pregnant 
must immediately discontinue study drug. The Investigator should counsel the subject, discussing 
any risks of continuing the pregnancy and any possible effects on the fetus. 
Although pregnancy itself is not regarded as an adverse event, the outcome will need to be 
documented. Any pregnancy occurring in a subject or subject’s partner from the time of consent 
to 30 days after the last dose of study combination must be reported. Any occurrence of 
pregnancy must be reported per SAE reporting timelines. All pregnancies will be followed for 
outcome, which is defined as elective termination of the pregnancy, miscarriage, or delivery of 
the fetus. Pregnancies with an outcome of live birth, the newborn infant will be followed until 30 
days old by completing will need to be reported per SAE reporting timelines. Any congenital 
anomaly/birth defect noted in the infant must be reported as a serious adverse event. 
Pregnancy report submission is to be done via eSAE application as “Other Important Medical Event”. 
 
 
 Paternal Exposure 
Pregnancy of the subject’s partners is not considered to be an adverse event. However, the 
outcome of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, 
normal birth or congenital abnormality) should if possible be followed up and documented. 
To capture information about a pregnancy from the partner of a male subject, the male subject’s 
partner consent must be obtained to collect information related to the pregnancy and outcome; 

 
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the male subject should not be asked to provide this information. A consent form specific to this 
situation must be used. The outcome of any conception occurring from the date of the first dose 
until 6 months after dosing ends should be followed up and documented. 
 
8 
RESPONSE CRITERIA 
 
 Measurement of Effect 
Efficacy Assessment 
Either computed tomography (CT), magnetic resonance imaging, or positron emission 
tomography-CT (that includes a contrast-enhanced CT component) of the head, neck, chest, and 
abdomen will be performed at screening, every 6 weeks (± 1 week) during the study, and at the 
end-of-treatment visit if a response assessment has not been performed within the last 30 days. 
Imaging of the pelvis is optional. Scans taken as part of standard medical practice up to 28 days 
prior to enrolment can be used for screening as long as they meet all study requirements.  
Tumor burden will be evaluated solely based on radiographic imaging per RECIST, version 1.1 
(17). For radiographic evaluations, the same method of assessment and the same technique 
(e.g., scan type, scanner, patient position, dose of contrast, injection/scan interval) should be 
used to characterize each identified and reported lesion at baseline and during study treatment 
and follow-up. 
For patients who stop study treatment in the absence of disease progression (e.g., experienced 
unexpected toxicity), scans should continue to be collected approximately every 6 weeks (± 1 
week) until disease progression or initiation of systemic antitumor therapy other than the study 
treatment, whichever is earlier. 
 
 Evaluation of Target Lesions  
Complete Response (CR):  Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). 
Partial Response (PR):  At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters. 
Progressive Disease (PD):  At least a 20% increase in the sum of the diameters of target 
lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is 
the smallest on study).  In addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5 mm (0.5 cm).  (Note:  the appearance of one or 
more new lesions is also considered progressions). 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
 

 
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 Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response assignment 
will depend on the achievement of both measurement and confirmation criteria. The response 
will be assessed by a radiologist collaborator and will be documented in the EMR and in the 
DMI database. 
 
For Patients with Measurable Disease (i.e., Target Disease) 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall 
Response when 
Confirmation is 
Required* 
CR 
CR 
No 
CR 
≥4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
≥4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-
PD/not evaluated 
No 
PR 
SD 
Non-CR/Non-
PD/not evaluated 
No 
SD 
Documented at least 
once ≥4 wks. from 
baseline** 
PD 
Any 
Yes or No 
PD 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
**    Only for non-randomized trials with response as primary endpoint. 
***   In exceptional circumstances, unequivocal progression in non-target lesions may be accepted 
as disease progression. 
 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic 
deterioration.”  Every effort should be made to document the objective progression even after 
discontinuation of treatment. 
 
For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
 
‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly 
used as an endpoint for assessment of efficacy in some trials so to assign this category when no 
lesions can be measured is not advised 
 
 Duration of Response 
Duration of overall response:  The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 

 
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recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented.  
Duration of stable disease:  Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since 
the treatment started, including the baseline measurements.  
 
 Progression-Free Survival 
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first. 
Response and progression will be evaluated in this study using the revised international criteria 
(RECIST version 1.1) proposed by the RECIST committee as well as the modified iRECIST 
guidelines.  Investigators should note the different requirements for confirmatory scans as well 
as follow up for the two criteria. 
 
9 
STATISTICAL CONSIDERATIONS 
This two-arm phase II open-label study is designed to evaluate the safety and activity of 
magrolimab, cetuximab and pembrolizumab administered in first-line (Cohort A) or magrolimab, 
cetuximab and docetaxel administered in second or third line for PD-1-refractory (Cohort B) R/M 
HNSCC patients. The primary outcome is the ORR per RECIST 1.1. The study will also 
characterize the safety profile of the triplet therapy. All patients who received at least one dose of 
any investigational agent will be included in the safety analysis. Only patients who have at least 
one re-staging radiological assessment will be included in the efficacy analysis.  
 Safety and Feasibility Monitoring  
To ensure patient safety, both Cohorts A and B will start with a staggered phase and a safety run-
in with two-predefined doses (Section 6, Table 3 and Table 4). Initially, 6 patients will be enrolled 
into Safety Run-in Cohort A and B to receive a starting regimen dose (dose 0).  A DLT evaluation 
period of 2 cycles (42 days) will occur. 
Even though no dose-dependent toxicities have been observed with magrolimab, in order to 
preserve the efficacious dose of the combination partner drugs, dose de-escalation may take 
place for magrolimab or other IMP, according to AEs attribution and physician discretion. Dose 
de-escalation decisions will be made as follows: 
- 
If no more than 2 of 6 DLT-evaluable patients experience a DLT during the DLT evaluation 
window (6 weeks), enrolment into phase 2 Cohorts 1 and 2 will begin at dose level 0. 

 
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- 
If 3 or more (> 50%) DLT-evaluable patients experience a DLT during the DLT evaluation 
window (6 weeks), another 6 patients will be enrolled at a lower dose and will be evaluated in 
the same manner to define the recommended dose for the combination regimen. 
- 
Dose de-escalation for Safety Run-in Cohorts A and B is presented in the Section 6 (Table 3). 
 
 Sample Size Determination 
 Safety Run-in Sample Size  
DLTs will be assessed during the first two cycles (6 weeks). The recommended dose is defined 
as the highest dose level in which 6 patients have been treated with less than 3 instances of DLT. 
It is anticipated that 6 to 12 eligible patients are required for the safety run-in phase of this trial. 
The patients treated with the selected dose in the safety run-in phase will be included in the phase 
II evaluation.  
Following assessment of the safety/tolerability of the triple combination regimen in the safety run-
in cohort, the staggered drug phase may be eliminated following recommendation of the Data and 
Safety Monitoring Committee. 
 
 Sample Size for Phase II Design for Cohort A: magrolimab, cetuximab, 
pembrolizumab in the first-line setting 
Bayesian Optimal Phase 2 (BOP2) design will be conducted after the safety run-in phase. For 
Cohort A, we will enroll up to 25 evaluable patients. The triplet regimen will have a target response 
rate (H1) of 55%. Since the expected ORR with single agent pembrolizumab is 17% and the ORR 
with cetuximab + pembrolizumab is 22-45%, we will consider an ORR of 30% or lower (H0) a 
failure and the new regimen will be rejected under this circumstance. The time to evaluate 
response is 6 months. Under these assumptions, Cohort A will include 12 evaluable patients in 
the first stage. If an objective response is observed in 3 or fewer  patients, the enrollment in Cohort 
A will be stopped. Otherwise, an additional 13 patients will be enrolled. The regimen will be 
considered worthy of further study if objective responses are observed in 12 or more patients in 
a total of 25 patients. This design has an alpha of 0.043 and power of 0.81.  The operating 
characteristics are given in the following table using the BOP2 web application (BOP2 V1.4.12.0), 
which is available at http://www.trialdesign.org.  
Scenario Response Rate Early Stopping (%) Claim Promising (%) Average Sample Size 
1 
0.30 
49.25 
4.32 
18.6 
2 
0.55 
3.56 
81.03 
24.5 
 
Specifically, we monitor the efficacy endpoint using the Bayesian optimal phase 2 (BOP2) design 
(Zhou, Lee and Yuan, 2017). Specifically, let 𝑛 denote the interim sample size and 𝑁 denote the 
maximum sample size. Let 𝑝𝑒𝑓𝑓 denote the objective response rate and define the null hypothesis 
𝐻0: 𝑝𝑒𝑓𝑓≤0.3, under which the treatment is deemed as unacceptable. We will stop enrolling 
patients and claim that the treatment is unacceptable if 

 
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𝑃𝑟(𝑝𝑒𝑓𝑓> 0.3|𝑑𝑎𝑡𝑎) < 𝜆(𝑛
𝑁)
𝛼
, 
where 𝜆=0.92 and 𝛼=0.74 are design parameters optimized to maximize power under the 
alternative hypothesis 𝐻1: 𝑝𝑒𝑓𝑓= 0.55, (i.e., the probability of correctly claiming that the treatment 
is acceptable under 𝐻1), while controlling the type I error rate (i.e., the probability of incorrectly 
claiming that the treatment is acceptable under 𝐻0) at 0.043. This optimization is performed 
assuming a vague prior Beta(0.3,0.7) for 𝑝𝑒𝑓𝑓. The above decision rule leads to the following 
stopping boundaries and yields a statistical power of 0.810 under 𝐻1. 
 
9.2.3  Sample Size for Phase II Design for Cohort B: mabrolimab, cetuximab, docetaxel in 
patient who have progressed on first-line systemic therapy 
Bayesian Optimal Phase 2 (BOP2) design will be conducted after the safety run-in phase. For 
Cohort B, we will include up to 24 evaluable patients. The target ORR (H1) is 45%, with an 
alternative hypothesis (H0) ORR of 20% (expected ORR with single agent cetuximab is 8-13%; 
in combination with taxane in the platinum-refractory setting, there is no prospective data; we 
estimate an ORR of 20% given the ORR to single agent docetaxel in this setting is 6% and 
cetuximab is thought to have an additive effect in combination of chemotherapy). The time to 
evaluate response is 6 months. Under these assumptions, Cohort B will include 14 evaluable 
patients in the first stage. If an objective response is observed in 3 or fewer patients, the 
enrollment of Cohort B will be stopped. Otherwise, an additional 10 patients will be enrolled. The 
regimen will be considered worthy of further study if objective responses are observed in 9 or 
more patients. This design has an alpha of 0.05 and power of 0.81. The operating characteristics 
are given in the following table using the BOP2 web application (BOP2 V1.4.12.0), which is 
available at http://www.trialdesign.org. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Scenario Response Rate Early Stopping (%) Claim Promising (%) Average Sample Size 
1 
0.20 
69.82 
3.44 
17.0 
2 
0.45 
6.32 
81.34 
23.4 
 
Specifically, we monitor the efficacy endpoint using the Bayesian optimal phase 2 (BOP2) design 
(Zhou, Lee and Yuan, 2017). Specifically, let 𝑛 denote the interim sample size and 𝑁 denote the 
maximum sample size. Let 𝑝𝑒𝑓𝑓 denote the objective response rate and define the null hypothesis 
𝐻0: 𝑝𝑒𝑓𝑓≤0.2, under which the treatment is deemed as unacceptable. We will stop enrolling 
patients and claim that the treatment is unacceptable if 
𝑃𝑟(𝑝𝑒𝑓𝑓> 0.25|𝑑𝑎𝑡𝑎) < 𝜆(𝑛
𝑁)
𝛼
, 

 
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where 𝜆=0.921 and 𝛼=0.42 are design parameters optimized to maximize power under the 
alternative hypothesis 𝐻1: 𝑝𝑒𝑓𝑓= 0.45, (i.e., the probability of correctly claiming that the treatment 
is acceptable under 𝐻1), while controlling the type I error rate (i.e., the probability of incorrectly 
claiming that the treatment is acceptable under 𝐻0) at 0.05. This optimization is performed 
assuming a vague prior Beta(0.2,0.8) for 𝑝𝑒𝑓𝑓. The above decision rule leads to the following 
stopping boundaries and yields a statistical power of 0.81 under 𝐻1: 
 
9.3.2: Toxicity Monitoring in Phase II 
To ensure patient safety, we will continue to monitor the treatment toxicity in Cohort A and Cohort 
B in the phase II part of the study, respectively. For each cohort, the study accrual will be 
suspended if Probability( ̂ > 0.3) ≥0.7 where 𝜃̂ is the estimated DLT rate. The default prior 
distribution Beta (0.5, 0.5) for  is used. The corresponding stopping boundaries for Cohort A with 
the maximum sample size of 25 are: ≥ 3/6 or ≥ 5/12 or ≥ 7/18 or ≥ 9/24 DLTs. The operating 
characteristics table for the design is shown below. As can be seen, the probability of early 
stopping is 1.8%, 46.1%, and 95.6% if the true DLT rates are 0.1, 0.3, and 0.5, respectively.  
Table 13. Operating characteristics of the early toxicity stopping for Cohort A with the maximum 
sample size of 25.   
 
 

 
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Table OC1: Overall Summary 
Scenario 
Prob.Of.Tox 
Prob.Early.Stop 
Prob.Declare.Tox 
Avg.N.Patients 
Avg.
1 
0.1 
0.0183 
0.0184 
24.6698 
2 
0.3 
0.4612 
0.4833 
18.3092 
3 
0.5 
0.9564 
0.9665 
9.5205 
 
Similarly, for Cohort B with the maximum sample size of 24, the corresponding stopping 
boundaries: ≥ 3/6 or ≥ 5/12 or ≥ 7/18 or ≥ 9/24 DLTs. The operating characteristics table for the 
design is shown below. As can be seen, the probability of early stopping is 1.8%, 49.0%, and 
97.5% if the true DLT rates are 0.1, 0.3, and 0.5, respectively.  
 
Table 14. Operating characteristics of the early toxicity stopping for Cohort B with the maximum 
sample size of 24.   
Table OC1: Overall Summary 
Scenario 
Prob.Of.Tox 
Prob.Early.Stop 
Prob.Declare.Tox 
Avg.N.Patients 
Avg.
1 
0.1 
0.0849 
0.0849 
22.4061 
2 
0.3 
0.5786 
0.6006 
13.8318 
3 
0.5 
0.9524 
0.9706 
6.9829 
 
The above calculations were performed by the Shiny apps at https://trialdesign.org/one-page-
shell.html#BTOX).   
 
 Stratification Factors 
N/A 
 

 
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Statistical Methods and Data Analysis 
Standard descriptive statistics will be provided for each continuous or categorical variable by 
cohorts and different dose levels that include arithmetic mean, standard deviation, median, 
quartiles, range for continuous variables; frequency counts and proportion for categorical 
variables as well as the 95% confidence intervals as appropriate. Boxplots, bar plots, variation of 
boxplots (e.g., swarmplot, violinplot), or heatmap etc. will be generated for visualization.  
 
9.4.1  Analysis of Primary Efficacy Endpoint 
The primary efficacy endpoint is the objective response rate by RECIST v1.1. ORR is defined as 
the percent of patients documented to have a confirmed CR or PR. The ORR and its exact 95% 
confidence interval will be calculated and presented by each cohort. Participants who are not 
evaluable for assessing the objective response will be considered as nonevaluable. 
 
9.4.2 Analysis of Secondary and Exploratory Endpoints 
N/A 
The Investigator is responsible for completing toxicity/efficacy summary reports and submitting 
them to the IND Sponsor. 
  
Run-In Phase: 
After the first 6 evaluable patients, per cohort, complete 2 cycles (42 days) of DLT evaluation 
period and then for every 6 evaluable patients, per cohort complete 2 cycles of treatment. IND 
Sponsor approval must be obtained prior to expanding/changing dose levels. 
Phase II: 
Toxicity summary: 
 
After the first 6 evaluable patients, per cohort, complete 2 cycles (42 days) of treatment and 
then for every 6 evaluable patients, per cohort complete 2 cycles of treatment. 
 
 Efficacy summary: 
 
Cohort A 
After the first 12 evaluable patients, complete 6 months of treatment in the first stage. Then 
after all 25 evaluable patients complete 6 months of treatment. 
 
 
Cohort B 
After the first 14 evaluable patients complete 6 months of treatment in the first stage. Then 
after the all 24 evaluable patients, complete 6 months of treatment. 
 
 
A copy of the cohort summary should be placed in the Investigator’s Regulatory Binder under 
“sponsor correspondence”. 
 

 
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Duration of response, PFS, and OS will be analyzed using the standard Kaplan-Meier method. 
Median survival time with its 95% CI and KM plots will be also provided. To identify biomarkers 
(Blood samples and tumor tissue samples) associated with response to the treatment, Chi-
squared/ Fisher’s exact tests, ANOVA and the Mann-Whitney U test will be used as appropriate. 
Logistic regression may be utilized to assess associations between biomarkers and response 
adjusting by baseline covariates. 
 
10 STUDY OVERSIGHT AND DATA REPORTING REQUIREMENTS 
This protocol is monitored at several levels, as described elsewhere in this section. The Protocol 
Principal Investigator is responsible for monitoring the conduct and progress of the clinical trial, 
including the ongoing review of accrual, patient-specific clinical and laboratory data, and routine 
and serious adverse events; reporting of expedited adverse events; and accumulation of reported 
adverse events from other trials testing the same drug(s).  The Protocol Principal Investigator and 
statistician always have access to the data. 
All Study Investigators at participating sites who register/enroll patients on a given protocol are 
responsible for timely submission of data via the mechanism described elsewhere in this section.  
All studies are also reviewed in accordance with the enrolling institution’s data safety monitoring 
plan. 
 
 Data and Safety Monitoring Committees 
MD Anderson’s Data and Safety Monitoring Committees are responsible for monitoring all 
investigator-initiated Pilot, Phase I, I/II, II single arm, as well as randomized Phase II or higher 
clinical trials. This trial will adhere to institutional data safety monitoring plans.  
 
 Clinical Trial Monitoring 
Regular monitoring of trial conduct will be conducted to ensure that the rights and well-being of 
trial participants are protected, that the reported trial data are accurate, complete, and verifiable, 
and that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with ICH GCP, and with applicable regulatory requirement(s).  
 
 Study Records Retention 
Essential/Source Documents may be maintained in electronic or via paper records. Electronic 
records must be maintained on an MD Anderson secured server accessed only by authorized 
research staff. Paper records must be maintained in a lockable room or cabinet accessed only by 
authorized research staff and must be made available in the event of an audit/inspection. 
Plan for continued storage of Essential/Source Documents consistent with protocol requirements, 
applicable regulations, Clinical Research contracts, and the Retention of Official Medical Records 
Policy (MD Institutional Policy ADM0386) will be followed. 
 

 
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 Consent Process and Documentation 
We will the Office of Clinical Research SOP 04: Informed Consent Process. 
11 DATA MANAGEMENT AND SHARING PLAN 
 
 Data Type 
Electronic case report forms will be used for this study, stored under the Data Management 
Initiative (DMI) database developed by the Department of Biostatistics. 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents include 
investigators’ Study Files and original patient clinical source documents generated at the study 
site.  
The investigator will ensure the Study Files are maintained, including the CRFs and query forms, 
protocol/amendments, IRB and regulatory approvals with associated correspondence, informed 
consents, study drug records, staff curriculum vitae, all correspondence, and other appropriate 
documents. 
Patient clinical source documents may include, but are not limited to, patient hospital/clinic 
records, physicians’ and nurses’ notes, appointment books, laboratory reports, ECGs, 
radiographs, pathology and special assessment reports. The investigator must assure that all 
original source documents are available to support monitoring activities. 
All laboratory and clinical data gathered in this protocol will be stored in a password protected 
database. All patient information will be handled using synonymous identifiers. Linkage to patient 
identity is only possible after accessing a password-protected database. Access to the database 
is only available to individuals directly involved in the study. 
 
 Related Tools, Software and/or Code 
N/A 
 Standards 
N/A 
 
 Data Preservation, Access, and Associated Timelines 
N/A 
 
 Access, Distribution, or Reuse Considerations 
N/A 
 

 
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 Data Collection and Management Responsibilities 
Data Capture: Data will be entered in the MD Anderson institutionally approved database (s).  All 
eligibility criteria must be satisfied prior to treatment initiation.  
All data collected will be used only for research purposes. Identifiers (name, medical record 
number, date of birth, treatment diagnosis, imaging tests, follow-up and death) may be collected 
but will be replaced by study numbers in the analytic files. Patient identifiers will be 
confidentially collected and securely maintained on a password protected server located behind 
the institutional firewall. Access to identifiers will follow IRB and MDA information security rules 
and regulations. The master database file will be accessible only to the Principal Investigator, 
approved collaborators, and research staff designated on the delegation of authority log. 
Accuracy of Data Collection: The MD Anderson Principal Investigator will be the final arbiter of 
response and toxicity, should a difference of opinion exist.    
 
 Oversight of Data Management and Sharing 
A protocol-specific monitoring plan will be developed by the IND Office. 
 
 Genomic Data Sharing Plan 
N/A 
 
 Incidental/Secondary Findings Disclosure Procedure 
N/A 
 
12 STATEMENT OF COMPLIANCE 
The trial will be conducted in compliance with the protocol and applicable state, local and federal 
regulatory requirements.  
Each engaged institution must have a current Federal-Wide Assurance (FWA) issued by the 
Office for Human Research Protections (OHRP) and must provide this protocol and the 
associated informed consent documents and recruitment materials for review and approval by an 
appropriate Institutional Review Board (IRB) or Ethics Committee (EC) registered with OHRP. 
Any amendments to the protocol or consent materials must also be approved before 
implementation.  
13 REFERECES 
1. 
Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G, Jr., et al. 
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for 
recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): 
a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-28. 
2. 
Ferris RL, Lenz HJ, Trotta AM, Garcia-Foncillas J, Schulten J, Audhuy F, et al. Rationale 
for combination of therapeutic antibodies targeting tumor cells and immune checkpoint 

 
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receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector 
stimulation. Cancer Treat Rev. 2018;63:48-60. 
3. 
Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, et al. Open-label, 
uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab 
as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of 
the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 
2007;25(16):2171-7. 
4. 
Chung CH, Bonomi MR, Steuer CE, Schell MJ, Li J, Johnson M, et al. Concurrent 
cetuximab (CTX) and nivolumab (NIVO) in patients with recurrent and/or metastatic 
(R/M) head and neck squamous cell carcinoma (HNSCC): Results of phase II study. 
Journal of Clinical Oncology. 2020;38(15_suppl):6515-. 
5. 
AG S, R C, D G, F W, DJ W, D A, et al. An open-label, non-randomized, multi-arm, phase 
II trial evaluating pembrolizumab combined with cetuximab in patients (pts) with 
recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): updated 
results of cohort 1 analysis. International Journal of Radiation Oncology. 
2020;106(5):P1121-2. 
6. 
Argiris A, Ghebremichael M, Gilbert J, Lee JW, Sachidanandam K, Kolesar JM, et al. 
Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in 
recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. 
J Clin Oncol. 2013;31(11):1405-14. 
7. 
Ferris RL, Blumenschein G, Jr., Fayette J, Guigay J, Colevas AD, Licitra L, et al. 
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 
2016;375(19):1856-67. 
8. 
Hitt R, Irigoyen A, Cortes-Funes H, Grau JJ, Garcia-Saenz JA, Cruz-Hernandez JJ, et al. 
Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line 
treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and 
neck. Ann Oncol. 2012;23(4):1016-22. 
9. 
Peron J, Ceruse P, Lavergne E, Buiret G, Pham BN, Chabaud S, et al. Paclitaxel and 
cetuximab combination efficiency after the failure of a platinum-based chemotherapy in 
recurrent/metastatic head and neck squamous cell carcinoma. Anticancer Drugs. 
2012;23(9):996-1001. 
10. 
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based 
chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116-
27. 
11. 
Pestana RC, Becnel M, Rubin ML, Torman DK, Crespo J, Phan J, et al. Response rates and 
survival to systemic therapy after immune checkpoint inhibitor failure in 
recurrent/metastatic head 
and 
neck 
squamous cell carcinoma. 
Oral 
Oncol. 
2020;101:104523. 
12. 
Saleh K, Daste A, Martin N, Pons-Tostivint E, Auperin A, Herrera-Gomez RG, et al. 
Response to salvage chemotherapy after progression on immune checkpoint inhibitors in 
patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. 
Eur J Cancer. 2019;121:123-9. 
13. 
Betancur PA, Abraham BJ, Yiu YY, Willingham SB, Khameneh F, Zarnegar M, et al. A 
CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation 
in breast cancer. Nature communications. 2017;8:14802. 

 
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14. 
Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, et al. CD47-
blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung 
cancer. The Journal of clinical investigation. 2016;126(7):2610-20. 
15. 
Fisher GA, Lakhani NJ, Eng C, Hecht JR, Bendell JC, Philip PA, et al. A phase Ib/II study 
of the anti-CD47 antibody magrolimab with cetuximab in solid tumor and colorectal cancer 
patients. J Clin Oncol. 2020;38(4_suppl):114-. 
16. 
Lakhani NJ, Patnaik A, Liao JB, Moroney JW, Miller DS, Fleming GF, et al. A phase Ib 
study of the anti-CD47 antibody magrolimab with the PD-L1 inhibitor avelumab (A) in 
solid tumor (ST) and ovarian cancer (OC) patients. J Clin Oncol. 2020;38(5_suppl):18-. 
17. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur 
J Cancer. 2009;45(2):228-47. 
18. 
Sikic BI, Lakhani N, Patnaik A, Shah SA, Chandana SR, Rasco D, et al. First-in-Human, 
First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With 
Advanced Cancers. Journal of clinical oncology : official journal of the American Society 
of Clinical Oncology. 2019;37(12):946-53. 
19. 
Administration 
FD. 
FDA 
approves 
new 
dosing 
regimen 
for 
cetuximab. 
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-new-
dosing-regimen-
cetuximab#:~:text=On%20April%206%2C%202021%2C%20the,the%20head%20and%
20neck%20(SCCHN.  Accessed 3/21/2022, 2022. 
 
14 APPENDICES 
A. Guidance for the Management of Anemia, Blood Cross-Matching, and Packed 
Red Blood Cell Transfusion Procedure  
Magrolimab binds to RBCs and leads to erythrophagocytosis. CD47 is a member of the Rh 
complex in the RBCs membrane. Therefore, when magrolimab binds to CD47, it is likely to 
interfere with routine blood bank tests needed in case of transfusion. Notify blood transfusion 
centers/blood banks of this interference with blood bank testing, and inform them that a patient 
will receive magrolimab.  
Participants with a low baseline hemoglobin level, especially those with cardiac history or risk 
factors, should be monitored closely after initial administrations of magrolimab as preexisting 
anemia could be exacerbated. Red blood cell transfusions ensure adequate hemoglobin level as 
per investigator clinical judgment. This, coupled with anemia from other causes in participants 
with cancers, means that care has to be taken with RBC cross-matching and packed RBC 
transfusions.  
After Exposure to Magrolimab  
For all elective RBC and platelet transfusions, use leukocyte-reduced and gamma-irradiated units 
per institutional guidelines.  
For RBC, phenotype/genotype matched units are preferred. However, CMV-seronegative units 
for CMV-seronegative patients will not be required for this study.  

 
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In case ABO/Rh type cannot be resolved, use pretreatment (historical) phenotype/genotype 
matched units for minor RBC antigens (CcDEe and Kk, to the feasible extent). Regarding the 
ABO type, institution can use historical blood group or O type as per the institutional guidelines.  
For emergency transfusions, the transfusion centers may consider using emergency Group O red 
cells if phenotype/genotype matched units are not available.  
Whenever possible, blood plasma therapy should be blood type specific. Platelets should be 
plasma-blood-type compatible whenever possible and, if not, should have been tested and found 
not to have high titer anti-A or anti-B. Otherwise, plasma and platelet products can be provided 
as per the institutional policy.  
A recent report has suggested that cross-match interference by RBCs due to treatment with 
magrolimab may be resolved by use of gamma-clone anti-IgG and multiple alloadsorptions with 
papain-treated RBC samples, pooled single donor apheresis platelets or commercial human 
platelet concentrates product if required {Troughton 2018, Velliquette 2019}.  
 
B. Guidance for the Management of Infusion Reactions and Late Hypersensitivity 
Reactions  
Infusion-related reactions are defined by the NCI CTCAE  as follows: a disorder characterized by 
adverse reaction to the infusion of pharmacological or biological substances. The time frame for 
IRR assessment is the 24-hour period beginning from the start of the magrolimab infusion. 
Recommendations for the management of IRRs are provided below.  
For Grade 1 symptoms (mild transient reaction; infusion interruption not indicated; intervention 
not indicated):  
· Remain at bedside and monitor participant until recovery from symptoms.  
For Grade 2 symptoms (infusion interruption indicated, but the participant responds promptly to 
symptomatic treatment [eg, antihistamines, nonsteroidal anti-inflammatory drugs, narcotics, 
corticosteroids, IV fluids] and prophylactic medications indicated for ≤ 24 hours):  
• 
Stop the magrolimab infusion, begin an IV infusion of normal saline, and treat the 
participant with diphenhydramine 50 mg IV (or equivalent) and/or 500 to 750 mg oral 
paracetamol/acetaminophen.  
• 
Remain at bedside and monitor participant until resolution of symptoms.  
• 
Corticosteroid therapy may also be administered at the discretion of the investigator.  
• 
If the infusion is interrupted, wait until symptoms resolve, then restart the infusion at 50% 
of the original infusion rate.  
• 
If no further complications ensue after 60 minutes, the rate may be increased to 100% of 
the original infusion rate. Monitor the participant closely.  
• 
If symptoms recur, then stop infusion and disconnect the participant from the infusion 
apparatus; no further magrolimab will be administered at that visit. The amount of study 
drug infused must be recorded on the case report form.  
• 
Premedications should be considered before any future infusions.  

 
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• 
Participants who experience an IRR of Grade 2 during the postinfusion observation period 
that does not resolve during that time should be observed for 24 hours or until the AE 
resolves or stabilizes, with vital sign measurements and additional evaluations as 
medically indicated for the management of the AE.  
For Grade 3 or Grade 4 symptoms where Grade 3 is described as prolonged (eg, not rapidly 
responsive to symptomatic medication and/or brief interruption of infusion); recurrence of 
symptoms following initial improvement; hospitalization indicated for other clinical sequelae (eg, 
renal impairment, pulmonary infiltrates); and where Grade 4 is described as life-threatening 
consequences; urgent intervention indicated:  
• 
Immediately discontinue infusion of magrolimab.  
• 
Begin an IV infusion of normal saline, and treat the participant as follows: Administer 
bronchodilators, epinephrine 0.2 to 1 mg of a 1:1000 solution for subcutaneous 
administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly for IV administration, 
and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV (or equivalent), as 
needed.  
• 
The participant should be monitored until the investigator is comfortable that the symptoms 
will not recur.  
• 
Participants who have Grade 4 infusions occurring with the first dose will be permanently 
discontinued from treatment.  
• 
Participants who have Grade 3 IRR with the first dose can be offered the opportunity to 
stay on study and must be given premedication prior to subsequent doses. In this setting, 
premedication with acetaminophen (650 to 1000 mg oral), diphenhydramine (25 to 50 mg 
oral or IV) and with dexamethasone (4 to 20 mg IV) as well, or comparable regimen, is 
recommended for the subsequent 2 doses. Long-term premedication can be discontinued 
if clinically indicated, for example, if the participant does not demonstrate further infusion 
reactions after multiple doses.  
• 
Participants who receive premedication with corticosteroids and still have a Grade 3 or 4 
infusion reaction will generally be permanently discontinued from treatment. However, 
specific study protocols should be followed for detailed guidance.  
• 
Investigators should follow their institutional guidelines for the treatment of anaphylaxis.  
In the case of late-occurring hypersensitivity symptoms (eg, appearance of localized or 
generalized pruritus after Day 1 but within 1 week after treatment), symptomatic treatment may 
be given (eg, oral antihistamine or corticosteroids).  
A premedication regimen (oral acetaminophen and diphenhydramine, or comparable regimen) is 
required before the initial doses of magrolimab and in case of repriming of the participant after > 
4 weeks interruption in magrolimab treatment. Specific premedication regimens for the 
combination therapies (cetuximab, rituximab, azacitidine, and avelumab) are described in the 
applicable study protocol.  
 

 
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C. Management of Pneumonitis  
Pneumonitis has been infrequently observed in participants receiving magrolimab. Generally, 
immune-related AEs have not been observed in clinical use with magrolimab. In contrast to T-cell 
checkpoint inhibitors (eg, pembrolizumab), magrolimab primarily exerts its antitumor efficacy 
through macrophage-mediated phagocytosis of tumor cells. Nonspecific T-cell or other host 
immune responses that are seen with T-cell checkpoint inhibitors have not been observed with 
magrolimab in nonclinical studies. Additionally, no related events of macrophage activation 
syndrome or hemophagocytic lymphohistiocytosis have been reported in clinical studies.  
In instances of suspected pneumonitis, first rule out noninflammatory causes (eg, infections). If a 
noninflammatory cause is identified, treat accordingly and continue therapy per protocol. Evaluate 
with imaging (eg, chest x-ray or CT) and pulmonary consultation.  
Management of potential pneumonitis is detailed in the Table below and follows Management of 
Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: 
American Society of Clinical Oncology Clinical Practice Guideline {Brahmer 2018}. Participants 
who experience Grade 3 or 4 pneumonitis will be permanently discontinued from study drug.  
  

 
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D. Magrolimab packaging, storage and handling 
 
Magrolimab will be provided in aqueous solution in 10 mL vials for intravenous (IV) administration. 
The drug product will be shipped (refrigerated) to a clinical distribution and packaging site for 
storage and distribution. The magrolimab drug product will be shipped to MDACC pharmacy for 
dose preparation.  
 
Vials containing magrolimab should be stored under refrigeration at 2 °C to 8 °C (36 °F to 46 °F) 
in an appropriate, locked room accessible only to pharmacy personnel, the principal investigator, 
or a duly designated person. Magrolimab should not be frozen and should be protected from light 
during storage. The drug product should not be shaken. Vials are single use containers and 
contain no preservatives; therefore, magrolimab administration should begin as soon as possible 
after preparation. 
 
The clinical dose will be prepared (diluted in saline) as an IV infusion through a standard infusion 
set. Doses in the range of 0.1 to 60 mg/kg will be infused in volumes ranging from 250 to 500 mL. 
The durations of the IV infusions of magrolimab will be up to 3 hours for doses of 1 to 60 mg/kg. 
Initial priming doses will be infused over a 3-hour period. 
 
The total exposure duration of the prepared magrolimab from the preparation start time and prior 
to the start of infusion, should not exceed: 
- 16 hours at refrigerated temperature, between 2 to 8°C (36°F to 46°F), and/or 
- 8 hours at room temperature (including equilibration time after refrigerated storage) 
 
The prepared drug solution can be stored at refrigerated temperature between 2°C to 8°C (36°F 
to 46°F) for up to 16 hours and / or stored at room temperature for up to 8 hours from the 
preparation start time. If stored at refrigerated temperature, the prepared drug solution should be 
equilibrated to room temperature for at least 1 hour. The total room temperature exposure prior 
to start of infusion including equilibration time should not exceed 8 hours. 
 
 
 
 
Solution Preparation and Administration 
The desired amount of magrolimab should be withdrawn from the vial(s) and diluted in an infusion 
bag with 0.9% sodium chloride for injection. The bag should be gently inverted to mix the solution. 
Magrolimab drug product vials and the diluted solution should be inspected visually before 
administration. If particulate matter or any coloration is noted, drug should not be administered, 
and the sponsor should be notified. 
Measures that minimize drug contact with the body should always be considered during handling, 
preparation, and disposal procedures. Any unused study drug should be disposed of in 
accordance with local requirements. 
 
Storage Conditions 
Based on available stability data, the drug product should be stored at 2 °C to 8 °C and protected 
from light. 
 
Stability 
Gilead’s policy is to monitor the stability of each formulation of study drug until the shelf life or a 
reevaluation period is established for the drug product. The stability studies cover the labeled 

 
MD Anderson Protocol Number: 2022-0903 
2022-0903 
Amendment 02 Version Date 7/20/23 
 
64 
storage conditions and, as appropriate, accelerated conditions. The stability of the drug product 
is tested at prescribed intervals to support the shelf life. Studies under accelerated conditions 
serve to identify any stability trend ahead of its occurrence under the labeled storage conditions. 
Through the combined approach of accelerated condition studies and long-term stability 
monitoring with frequent testing, the purported identity, strength, and quality will be assured for 
all drug product lots used in clinical studies.