Phase 1 Trial of Hu5F9-G4 (Magrolimab) Combined With Dinutuximab in Children and Young Adults With Relapsed and Refractory Neuroblastoma or Relapsed Osteosarcoma
Phase: PHASE1
Conditions: High Risk Neuroblastoma, Recurrent Neuroblastoma, Recurrent Osteosarcoma, Refractory Neuroblastoma, Resectable Osteosarcoma
Sponsor: National Cancer Institute (NCI)

  
 
 
 
i 
 
 
 
Pediatric Early Phase 
Clinical Trial 
Network (PEP-CTN) and  
Developmental 
Therapeutics (DVL) 
Chair 
Brenda J. Weigel, M.D. 
weige007@umn.edu 
 
PEP-CTN and  
Developmental 
Therapeutics (DVL) 
Vice Chair  
Elizabeth Fox, M.D. 
elizabeth.fox@stjude.org 
 
PEP-CTN Operations  
Data & Statistics Center 
Director 
Thalia Beeles, MPH 
tbeeles@childrensoncolog
ygroup.org 
 
PEP-CTN Statistician  
Charles G. Minard, Ph.D. 
minard@bcm.edu 
 
 
PEP-CTN and  
DVL Chair’s Office 
University of Minnesota/ 
Masonic Cancer Center 
Masonic Children’s 
Hospital 
420 Delaware Street, SE 
MMC 366 
Minneapolis, MN  55455 
 
P 612 626 5501 
F 612 624 3913 
 
 
Children’s Oncology Group 
Group Chair 
Douglas S. Hawkins, MD 
Seattle Children's Research  
Institute 
doug.hawkins@seattlechild
rens       
.org  
 
Children’s Oncology Group 
Group Vice Chair 
Lia Gore, MD 
Children's Hospital 
Colorado 
lia.gore@cuanschutz.edu  
 
 
 
PEP-CTN Operations Data 
& 
Statistics Center 
1333 S. Mayflower Avenue 
Suite 260 
Monrovia, CA 91016 
 
P 626 241 1500 
F 626 445 4334 
 
 
A National Cancer Institute-  
supported member group  
February 2, 2024 
 
Martha Kruhm, MS, RAC 
Head, Protocol and Information Office  
Operations and Informatics Branch 
Cancer Therapy Evaluation Program 
Division of Cancer Treatment and Diagnosis 
National Cancer Institute 
Executive Plaza North Room 730 
Bethesda, MD 20892 
 
Dear Ms. Kruhm, 
 
Enclosed please find Amendment #8 to protocol PED-CITN-03, Phase 1 Trial of Hu5F9-
G4 (magrolimab) combined with dinutuximab in children and young adults with relapsed 
and refractory neuroblastoma or relapsed osteosarcoma.  
 
Amendment #8 is in response to a request for a rapid amendment from Dr. Helen Chen 
(helen.chen@nih.gov). The amendment provides new and/or modified risk information 
associated with hu5F9-G4 and revises the Comprehensive Adverse Events and Potential 
Risks (CAEPR) list. Sections of the protocol and consent were updated to reflect these 
changes.  
 
Administrative changes have been made; specific changes are detailed in the Summary of 
Changes table below. Minor administrative updates (such as the correction of 
typographical errors, spelling, or updates to the numbers of referenced sections) are 
tracked in the protocol but not specified. 
 
 
Please let me know if you have any questions or need additional information. 
 
Sincerely, 
 
 
Emma Archuleta, Protocol Coordinator (for) 
Robbie G. Majzner, PED-CITN-03 Study Chair,  
Brenda Weigel, M.D., PEP-CTN Chair 
 

 
ii 
 
SUMMARY OF CHANGES: PROTOCOL 
In accordance with the above discussion, the following specific revisions have been made to the protocol. 
Additions are in boldfaced font and deletions in strikethrough font. 
# 
Section 
Page(s) 
Change 
1.  
General 
All 
Updated protocol version date in the footer.  
2.  
Cover Page 
1 
Updated version date and amendment number.  
3.  
Contact 
Information 
1 
9 
Updated study committee information  
4.  
Table of 
Contents 
5-8 
Updated for re-pagination.  
5.  
10.1.1.1 
86-87 
The CAEPR has been updated to (Version 2.2, December 6, 2023) 
in response to a rapid request for amendment: 
• 
Added New Risk:   
• 
Likely: Hypotension 
• 
Less Likely: Abdominal pain; Arthralgia; Cough; 
Dizziness; Generalized edema; Hypokalemia; 
Lymphocyte count decreased; Lung infection; 
Neutrophil count decreased; Pruritis; White blood 
cell count decreased  
• 
Rare but Serious: Blood and lymphatic system 
disorders - Other (red blood cell agglutination); 
Hemolysis  
• 
Also Reported on Hu5F9-G4 Trials But With 
Insufficient Evidence for Attribution: Alkaline 
phosphatase increased; Aspartate 
aminotransferase increased; Conjunctivitis; 
Constipation; Edema cerebral; Epistaxis; 
Hypertension; Hypophosphatemia; Intracranial 
hemorrhage; Tumor pain; Nervous system disorders 
- Other (cerebral hemorrhage); Pain; Pneumonitis; 
Serum sickness; Small intestinal obstruction; 
Thromboembolic event; Urinary tract infection 
 
• 
Increase in Risk Attribution:   
• 
Changed from Less Likely to Likely: Fatigue  
• 
Changed to Less Likely from Also Reported on 
Hu5F9-G4 Trials But With Insufficient Evidence for 
Attribution: Back pain; Dyspnea; Febrile neutropenia 
• 
Changed to Rare but Serious from Also Reported 
on Hu5F9-G4 Trials But With Insufficient Evidence 
for Attribution: Sepsis 
 
• 
Decrease in Risk Attribution:    
• 
Changed from Less Likely to Also Reported on 
Hu5F9-G4 Trials But With Insufficient Evidence        
for Attribution: Dry Skin; Hypomagnesemia; Rash 
acneiform   

 
iii 
 
 
• 
Modified Specific Protocol Exceptions to Expedited 
Reporting (SPEER) reporting requirements:  
• 
Added: Abdominal pain Anorexia; Blood bilirubin 
increased Febrile neutropenia; Hypokalemia; 
Lymphocyte count decreased, Neutrophil count 
decreased, Platelet count decreased, White blood 
cell decreased 
 
 
 
 
 
 
 
 

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PED-CITN-03 
 
 Phase 1 Trial of Hu5F9-G4 (magrolimab) combined with dinutuximab in children and 
young adults with relapsed and refractory neuroblastoma or relapsed osteosarcoma 
 
Lead Organization: COG Pediatric Early Phase Clinical Trials Network (PEP-CTN) 
 
NCI Supplied Agents: Hu5F9-G4 (magrolimab); NSC 809249,Dinutuximab,  NSC 764038, IND # 
IND Sponsor for Hu5F9-G4 (magrolimab) and Dinutuximab: DCTD, NCI 
 
 
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, AND SHOULD NOT BE COPIED, REDISTRIBUTED OR USED 
FOR ANY OTHER PURPOSE. MEDICAL AND SCIENTIFIC INFORMATION CONTAINED WITHIN THIS PROTOCOL IS 
NOT INCLUDED TO AUTHORIZE OR FACILITATE THE PRACTICE OF MEDICINE BY ANY PERSON OR ENTITY. 
RESEARCH MEANS A SYSTEMATIC INVESTIGATION, INCLUDING RESEARCH DEVELOPMENT, TESTING AND 
EVALUATION, DESIGNED TO DEVELOP OR CONTRIBUTE TO GENERALIZABLE KNOWLEDGE. THIS PROTOCOL IS 
THE RESEARCH PLAN DEVELOPED BY THE CHILDREN’S ONCOLOGY GROUP TO INVESTIGATE A PARTICULAR 
STUDY QUESTION OR SET OF STUDY QUESTIONS AND SHOULD NOT BE USED TO DIRECT THE PRACTICE OF 
MEDICINE BY ANY PERSON OR TO PROVIDE INDIVIDUALIZED MEDICAL CARE, TREATMENT, OR ADVICE TO ANY 
PATIENT OR STUDY SUBJECT. THE PROCEDURES IN THIS PROTOCOL ARE INTENDED ONLY FOR USE BY CLINICAL 
ONCOLOGISTS IN CAREFULLY STRUCTURED SETTINGS, AND MAY NOT PROVE TO BE MORE EFFECTIVE THAN 
STANDARD TREATMENT. ANY PERSON WHO REQUIRES MEDICAL CARE IS URGED TO CONSULT WITH HIS OR HER 
PERSONAL PHYSICIAN OR TREATING PHYSICIAN OR VISIT THE NEAREST LOCAL HOSPITAL OR HEALTHCARE 
INSTITUTION. 
 
STUDY CHAIR 
Robbie G Majzner, MD 
Dana-Farber/Harvard Cancer Center 
Phone: (857) 215-1923  
E-mail: robbie_majzner@dfci.harvard.edu 
 
 
 
 
 
 
 
Activated: 
04/16/2021 
Version Date: 
02/02/2024 
Closed: 
 
Amendment: 
8 

PED-CITN-03 
 
               
 
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Page 2 
 
 
 
CONTACT INFORMATION 
For Regulatory Requirements: 
For patient enrollments: 
For Data Submission: 
Regulatory documentation must 
be submitted to the Cancer Trials 
Support Unit (CTSU) via the 
Regulatory Submission Portal. 
(Sign in at https://www.ctsu.org, 
and select the Regulatory > 
Regulatory Submission.)  
 
Institutions with patients waiting 
that are unable to use the Portal 
should alert the CTSU Regulatory 
Office immediately by phone or 
email: 1-866-651-CTSU (2878) 
or CTSURegHelp@coccg.org to 
receive further instruction and 
support. 
 
Contact the CTSU Regulatory 
Help Desk at 1-866-651-CTSU 
(2878), or 
CTSURegHelp@coccg.org for 
regulatory assistance. 
Refer to the patient enrollment 
section of the protocol for 
instructions on using the 
Oncology Patient Enrollment 
Network (OPEN). OPEN can be 
accessed at 
https //www.ctsu.org/OPEN_SY
STEM/ or 
https //OPEN.ctsu.org. 
 
Contact the CTSU Help Desk 
with any OPEN-related 
questions at 
ctsucontact@westat.com. 
 
 
Data collection for this study 
will be done exclusively through 
Medidata Rave. Please see the 
Data Submission Schedule in the 
CRF packet for further 
instructions.  
 
The most current version of the study protocol must be downloaded from the protocol-specific page 
located on the CTSU members’ website (https://www.ctsu.org). Access to the CTSU members’ website 
is managed through the Cancer Therapy and Evaluation Program – Identity and Access Management 
(CTEP-IAM) registration system and requires logging in with a CTEP-IAM username and password or 
linked ID.me account (ID.me accounts are required for all newly created CTEP-IAM accounts and by 
July 1, 2023 for all users)..  
 
Permission to view and download this protocol and its supporting documents is restricted and is based 
on the person and site roster assignment housed in the Roster Maintenance application and in most 
cases viewable and manageable via the Roster Update Management System (RUMS) on the Cancer 
Trials Support Unit (CTSU) members’ website..  
For clinical questions (i.e., patient eligibility or treatment-related) 
Contact the PI of the Lead Protocol Organization 
For nonclinical questions (i.e., unrelated to patient eligibility, treatment, or clinical data 
submission) 
Contact the CTSU Help Desk by phone or email: 
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  
All calls and correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Website is located at https://www.ctsu.org 
 
 

PED-CITN-03 
 
               
 
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SCHEMA 
 
Figure 1: Overall Trial Schema 
 
 
 
 

PED-CITN-03 
 
               
 
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Figure 2: Trial Schedule Schema 
 
 
 

 
 
 
                                              
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TABLE OF CONTENTS 
SCHEMA 
3 
STUDY COMMITTEE .....................................................................................................9 
1 
OBJECTIVES ............................................................................................................10 
1.1 
Primary Objectives .................................................................................................10 
1.2 
Secondary Objectives .............................................................................................10 
1.3 
Exploratory Objectives ..........................................................................................10 
2 
BACKGROUND ........................................................................................................11 
2.1 
Introduction and Rationale .....................................................................................11 
2.2 
Rationale for Combining GD2 and CD47 in Neuroblastoma and Osteosarcoma .17 
2.3 
Correlative Studies Background ............................................................................18 
3 
PATIENT ELIGIBILITY ...........................................................................................19 
3.1 
Eligibility Inclusion Criteria ..................................................................................19 
3.2 
Exclusion Criteria ..................................................................................................21 
3.3 
Inclusion of Women and Minorities ......................................................................23 
4 
REGISTRATION PROCEDURES ............................................................................23 
4.1 
Investigator and Research Associate Registration with CTEP ..............................23 
4.2 
CTSU Registration Procedures ..............................................................................24 
4.3 
Patient Enrollment .................................................................................................26 
4.4 
General Guidelines .................................................................................................27 
5 
BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES .................................29 
5.1 
Exploratory/Ancillary Correlative Studies ............................................................35 
5.2 
Processing and Storage of Specimens at EET Biobank .........................................36 
5.3 
Summary Table for Specimen Collection ..............................................................37 
5.4 
Specimen Procurement Kits and Scheduling .........................................................41 
5.5 
Specimen Labeling.................................................................................................42 
5.6 
Specimen Collection ..............................................................................................43 
5.7 
Shipping Specimens from Clinical Sites to the EET Biobank ...............................45 
5.8 
Shipping Specimens from Clinical Sites to Specific Laboratories ........................48 
6 
TREATMENT AND IMAGING PLAN ....................................................................49 
6.1 
Agent Dose and Administration.............................................................................49 
6.2 
Regimen Description and Supportive Care Guidelines .........................................52 
6.3 
Definition of Dose-Limiting Toxicity ....................................................................59 
6.4 
Dose Expansion Cohorts ........................................................................................60 
6.5 
Criteria for Removal from Protocol Therapy and Off Study Criteria ....................61 
6.6 
Duration of Follow-Up ..........................................................................................62 
6.7 
General Concomitant Medication ..........................................................................63 
6.8 
Contraception .........................................................................................................63 
7 
DOSING DELAYS/DOSE MODIFICATIONS ........................................................64 

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7.1 
Dosage modification for Hu5F9-G4 (magrolimab) ...............................................65 
7.2 
Hu5F9-G4 (Magrolimab) AE Management and Dose Interruption Guidelines ....66 
7.3 
Dinutuximab (Unituxin®) AE Management and Dose Modification Guidelines ..70 
8 
AGENT INFORMATION .........................................................................................75 
8.1 
CTEP IND Agent(s) ...............................................................................................76 
9 
STATISTICAL CONSIDERATIONS .......................................................................80 
9.1 
Responsibility for Analyses ...................................................................................80 
9.2 
Study Design/Endpoints.........................................................................................80 
9.3 
Sample Size/Accrual Rate ......................................................................................83 
9.4 
Demographics ........................................................................................................83 
9.5 
Analysis of Secondary Endpoints ..........................................................................84 
10 ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS ......................85 
10.1 
Comprehensive Adverse Events and Potential Risks List(s) (CAEPRs) ...............85 
10.2 
Adverse Event Characteristics ...............................................................................91 
10.3 
Expedited Adverse Event Reporting ......................................................................91 
10.4 
Routine Adverse Event Reporting .........................................................................93 
10.5 
Pregnancy ...............................................................................................................94 
10.6 
Secondary Malignancy ...........................................................................................94 
10.7 
Second Malignancy ................................................................................................94 
11 STUDY CALENDAR ................................................................................................95 
12 EVALUATION CRITERIA .....................................................................................103 
12.1 
Antitumor Effect – Osteosarcoma (Measurable disease) .....................................103 
12.2 
Response Criteria for Patients with Neuroblastoma (measurable or evaluable disease) 107 
13 STUDY OVERSIGHT AND DATA REPORTING / REGULATORY 
REQUIREMENTS ...................................................................................................112 
13.1 
Data and Safety Monitoring Plan .........................................................................112 
13.2 
Data Submission / Data Reporting .......................................................................112 
13.3 
CTEP Multicenter Guidelines ..............................................................................114 
13.4 
CRADA/CTA/CSA..............................................................................................115 
14 REFERENCES .........................................................................................................117 
APPENDIX A: PERFORMANCE STATUS CRITERIA ...............................................121 
APPENDIX B: FORMULA TO ESTIMATE RENAL FUNCTION USING SERUM 
CREATININE ..........................................................................................................122 
APPENDIX C: CTEP MULTICENTER GUIDELINES ................................................123 
APPENDIX D: PRE-BIOPSY ASSESSMENT ..............................................................125 
APPENDIX E: PATIENT CLINICAL TRIAL WALLET CARD..................................126 

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APPENDIX F: YOUTH INFORMATION SHEETS ......................................................127 
APPENDIX G: PHARMACOKINETIC WORKSHEET FOR MAGROLIMAB, ARM A131 
APPENDIX H: PHARMACOKINETIC WORKSHEET FOR MAGROLIMAB, ARM B135 
APPENDIX I: ANTI-DRUG ANTIBODY (ADA) WORKSHEET FOR MAGROLIMAB138 
APPENDIX J: FCR RECEPTOR POLYMORPHISM WORKSHEET FOR ARM A ...141 
APPENDIX K: FCR RECEPTOR POLYMORPHISM WORKSHEET for ARM B .....142 
APPENDIX L:  KIR PHENOTYPING WORKSHEET FOR ARM A ...........................143 
APPENDIX M: KIR PHENOTYPING WORKSHEET FOR ARM B ...........................144 
APPENDIX N: HUMAN ANTI-CHIMERA ANTIBODIES (HACA) TESTING 
WORKSHEET for ARM A ......................................................................................145 
APPENDIX O: HUMAN ANTI-CHIMERA ANTIBODIES (HACA) TESTING 
WORKSHEET for ARM B ......................................................................................146 
APPENDIX P:  LUMINEX FOR PERIPHERAL CYTOKINES WORKSHEET FOR 
ARM A 147 
APPENDIX Q:  LUMINEX FOR PERIPHERAL CYTOKINES WORKSHEET FOR 
ARM B 151 
APPENDIX R:  CYTOF FOR PERIPHERAL IMMUNE SUBSETS WORKSHEET FOR 
ARM A 155 
APPENDIX S:  CYTOF FOR PERIPHERAL IMMUNE SUBSETS WORKSHEET FOR 
ARM B 158 
APPENDIX T: SAMPLE BANKING WORKSHEET FOR ARM A ............................161 
APPENDIX U: SAMPLE BANKING WORKSHEET FOR ARM B ............................164 
APPENDIX V: CENTRAL MONITORING PLAN .......................................................167 
 
Table of Figures 
 
Figure 1: Overall Trial Schema ........................................................................................................................... 3 
Figure 2: Trial Schedule Schema ......................................................................................................................... 4 
Figure 3: Anti-GD2 and anti-CD47 antibodies result in synergistic activity and prolonged tumor 
clearance in xenograft models of neuroblastoma ............................................................................................. 17 
Figure 4: Anti-GD2 and anti-CD47 antibodies result in synergistic activity in xenograft models of 
osteosarcoma ....................................................................................................................................................... 18 
 

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Table of Tables 
 
Table 1: RCR Required Documentation........................................................................................................... 23 
Table 2: List of Biomarkers in Order of Priority ............................................................................................ 29 
Table 3: Summary Table for Specimen Collection .......................................................................................... 37 
Table 4: Doses for Hu5F9-G4 (magrolimab) and Dinutuximab during Dose Finding Cohort (Cycle 1) ... 51 
Table 5: Regimen Description for Dose Finding Cohort (Arm A) ................................................................. 52 
Table 6: Regimen Description for Arm B - Expansion Cohorts B1 – B3 (Confirmed Neuroblastoma, 
Evaluable Neuroblastoma, Measurable Osteosarcoma), Cohort B4 (Resectable, pulmonary only relapsed 
osteosarcoma**) - Non-staged resections and Cohort B4 – Staged resections prior to surgery and post 
resection with restart within 4 weeks of last dose ............................................................................................ 54 
Table 7: Regimen Description for Arm B - Expansion Cohort B4 Staged Resection – Post Resection with 
Delayed Restart > 4 weeks (Resectable, pulmonary only relapsed osteosarcoma**) ........................................ 55 
Table 8: Adverse Reactions Requiring Permanent Discontinuation of Dinutuximab ................................. 71 

                              
 
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STUDY COMMITTEE 
STUDY CHAIR 
Robbie G Majzner, MD  
Hematology/Oncology 
Dana-Farber/Harvard Cancer Center 
Phone:        (857) 215-1923 
E-mail:  robbie_majzner@dfci.harvard.edu 
 
STUDY VICE CHAIR 
Suzanne Shusterman 
Hematology/Oncology 
Dana-Farber/Harvard Cancer Center 
Phone: 
(617) 632-4901 
E-mail: 
Suzanne_Shusterman@dfci.harvard.edu 
 
STUDY STATISTICIAN 
Charles Minard, PhD 
Biostatistics 
Baylor College of Medicine/Dan L Duncan 
Comprehensive Cancer Center 
Phone: 
(713) 798-2353 
E-mail: 
minard@bcm.edu 
 
 
COG PHARMACIST 
Olga Militano, PharmD 
Children's Oncology Group 
Phone: 
(626) 241 - 1517 
E-mail: omilitano@childrensoncologygroup.org 
 
 
 
 
STUDY COMMITTEE MEMBERS 
Brenda J. Weigel, MD 
Chair, PEP-CTN 
University of Minnesota Medical Center - Fairview 
Phone:  (612) 616-5501 
E-mail: weige007@umn.edu 
 
Elizabeth Fox, MD 
Vice Chair, PEP-CTN 
St. Jude Children’s Research Hospital 
Phone: (910) 595-3300 
E-mail: elizabeth.fox@stjude.org 
 
STUDY PHARMACOLOGIST  
Joel M. Reid, Ph.D. 
Mayo Clinic 
Phone: (507) 284-0822 
Email:  reid@mayo.edu 
 
COG PEP-CTN RESEARCH COORDINATOR 
Sarah Arendt, MPH 
Children's Oncology Group 
Phone: (626) 241-1564 
E-mail: 
sarendt@childrensoncologygroup.org 
 
COG PEP-CTN PROTOCOL COORDINATOR 
Emma Archuleta, BS 
Children's Oncology Group 
Phone: (626) 241-1645 
E-mail: earchuleta@childrensoncologygroup.org 
 
 
AGENT 
NSC# 
Supplier 
Hu5F9-G4 
(magrolimab) 
Dinutuximab 
809249 
764038 
NCI 
NCI 
IND Number:  
IND Sponsor: CTEP 

                              
 
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Version Date: 02/02/2024 
 
 
Page 10 
 
 
 
This trial is covered by a Certificate of Confidentiality from the federal government, which will help us protect the 
privacy of our research subjects. The Certificate protects against the involuntary release of information about your 
subjects collected during the course of our covered studies. The researchers involved in the studies cannot be forced to 
disclose the identity or any information collected in the study in any legal proceedings at the federal, state, or local level, 
regardless of whether they are criminal, administrative, or legislative proceedings. However, the subject or the researcher 
may choose to voluntarily disclose the protected information under certain circumstances. For example, if the subject or 
his/her guardian requests the release of information in writing, the Certificate does not protect against that voluntary 
disclosure. Furthermore, federal agencies may review our records under limited circumstances, such as a DHHS request 
for information for an audit or program evaluation or an FDA request under the Food, Drug and Cosmetics Act. 
The Certificate of Confidentiality will not protect against mandatory disclosure by the researchers of information on 
suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others. 
 
1 
OBJECTIVES 
 
1.1 
Primary Objectives 
 
1.1.1 
Determine the safety and tolerability of Hu5F9-G4 (magrolimab) in combination with dinutuximab in children 
and young adults with relapsed/refractory (R/R) neuroblastoma (NBL) or relapsed osteosarcoma. 
 
1.1.2 
Determine the recommended phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) given in combination with 
dinutuximab in children and young adults. 
 
1.1.3 
Determine the safety and feasibility of administering Hu5F9-G4 (magrolimab) in combination with dinutuximab 
to patients that undergo pulmonary resection of metastatic osteosarcoma within three weeks of surgery. 
 
1.2 
Secondary Objectives 
 
1.2.1 
Determine the pharmacokinetics (PK) of Hu5F9-G4 (magrolimab) in children and young adults. 
 
1.2.2 
Evaluate the Event Free Survival (EFS) in two cohorts of patients who are treated at the recommended phase 2 
dose (RP2D) (measurable relapsed osteosarcoma and patients with pulmonary relapse undergoing resection) and 
compare to historical controls (Lagmay et al., 2016).  
 
1.2.3 
Observe and record anti-tumor activity. 
 
1.2.4 
Evaluate the Overall Response Rate (ORR) of patients in the NBL cohorts (Measurable R/R NBL and Evaluable 
R/R NBL) and osteosarcoma patients (measurable relapsed osteosarcoma) in the expansion cohorts treated at the 
RP2D. 
 
1.3 
Exploratory Objectives 
 

                              
 
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1.3.1 
To explore biomarkers of response and resistance including genomic (CD47 expression, FcR polymorphisms, 
SIRPa polymorphisms, and KiR phenotype) and immunologic (dinutuximab HACA, magrolimab ADA, peripheral 
and bone marrow immune subsets, and circulating cytokines). 
 
1.3.2 
To explore biomarkers of response in the tumor microenvironment through MIBI on resected tissue or archival 
tissues including comparison of pre- and post- treatment tumor tissues from patients undergoing staged resection of 
pulmonary osteosarcoma. 
 
2 
BACKGROUND 
 
2.1 
Introduction and Rationale 
 
2.1.1 
Relapsed and Refractory Osteosarcoma and Neuroblastoma (NBL) in Children and Young Adults 
 
Children diagnosed with metastatic or relapsed solid tumors have few therapeutic options and often die from their disease 
(Perkins, Shinohara, DeWees, & Frangoul, 2014), (Ceschel et al., 2006). Despite the use of multiagent chemotherapy along 
with radiation and surgery, survival rates for patients with most high-risk solid tumors have not significantly improved since 
the 1980’s. This is most evident for osteosarcoma, a bone tumor occurring in children, for which there has been little 
improvement in overall survival for the past forty years. Adding chemotherapeutic agents such as Ifosfamide to already 
intense chemotherapy regimens has not resulted in a survival benefit (Meyers et al., 2008). This is emblematic of pediatric 
high-risk solid tumors in general, as the success of multi-agent chemotherapy in pediatric oncology appears to be reaching 
a plateau. The sole solid tumor exception to this trend is neuroblastoma, where the adoption of anti-GD2 monoclonal based 
immunotherapy into frontline protocols has significantly increased overall survival rates among high risk patients (Yu et 
al., 2010). However, despite the use of anti-GD2 antibodies, more than forty percent of neuroblastoma patients ultimately 
die from their disease. 
 
2.1.2 
Neuroblastoma and Targeting GD2 
 
Neuroblastoma, a tumor that arises from neural crest cells, occurs almost exclusively in children and accounts for 10-15% 
of pediatric cancer deaths. Approximately half of neuroblastoma patients are diagnosed with high risk disease (loosely 
defined as metastatic disease in children >18 months). These patients undergo intensive chemotherapy, surgery, autologous 
stem cell transplant, radiotherapy, immunotherapy, and differentiation therapy. Despite this multimodal approach, only 
approximately 50% of patients are cured of their disease (Yu et al., 2010). 
 
The adoption of anti-GD2 antibodies has revolutionized the care of children with neuroblastoma. However, early trials of 
these antibodies largely demonstrated activity in bone marrow only disease and not in patients with bulky disease (Frost et 
al., 1997). The phase 3 trial of ch14.18 that resulted in FDA approval (dinutuximab) tested this antibody in a population of 
patients with no detectable disease (Yu et al., 2010). Multiple studies have demonstrated that GD2 antibody monotherapy 
does not mediate significant effect against established, bulk tumor. Therefore, there is an urgent need to enhance the potency 
of this agent. Recently, in a randomized control trial, the combination of dinutuximab with chemotherapy 
(irinotecan/temozolomide) was demonstrated to mediate objective responses in 53% of patients with recurrent 
neuroblastoma, compared to a 6% response rate in patients receiving irinotecan/temozolomide with temsirolimus (Mody et 
al., 2017). Thus, there is a clear potential to enhance the efficacy of this agent in neuroblastoma. 
 
2.1.3 Osteosarcoma and Targeting GD2 
 
Outcomes for patients with resectable, non-metastatic osteosarcoma have plateaued at approximately 70% using 
surgery plus multiagent chemotherapy. There is consensus that further progress against this disease requires the 

                              
 
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development of targeted therapies that overcome resistance to standard cytotoxic agents. For patients who present 
with metastatic osteosarcoma or who have unresectable disease, outcomes are dismal with <20% survival and little progress 
has been made over the last several decades (Meyers & Gorlick, 1997). Similarly, patients with recurrent osteosarcoma have 
survival rates of approximately 20-30%, even after resection with or without chemotherapy (Meyers & Gorlick, 1997). 
There are few salvage therapies or options for experimental therapies for osteosarcoma.  
 
We have found that 18/18 (100%) of osteosarcoma samples tested expressed GD2 with 15/18 (83%) expressed at high levels 
(Long et al., 2016). This stands in contrast to the other solid tumor histologies we studied, including Ewings sarcoma and 
rhabdomyosarcoma, where we observed nearly no staining on primary samples (2/15 for rhabdomyosarcoma; 7/35 for 
Ewings sarcoma). Similarly, a group at Memorial Sloan Kettering stained frozen osteosarcoma samples with their own 
validated anti-GD2 antibody (3F8) and found that 16/19 (84%) osteosarcomas expressed GD2, while only 2/18 (10%) of 
desmoplastic small round cell tumor samples were GD2 positive (Dobrenkov, Ostrovnaya, Gu, Cheung, & Cheung, 2016). 
Finally, an additional study found that at recurrence 31 of 32 samples (97%) from patients with osteosarcoma expressed 
GD2, the majority of which were expressed at high levels (Poon et al., 2015). The results demonstrate that the majority of 
osteosarcomas express GD2, in contrast to other sarcomas such as Ewing sarcoma and rhabdomyosarcoma. Anti-GD2 
antibodies are currently in clinical trials for osteosarcoma (NCT02484443) and there have been several reported responses 
to anti-GD2 antibodies in this disease including a complete response to a monoclonal antibody and a PET response to a 
GD2xCD3 bispecific antibody (Frost et al., 1997), (Murray et al., 1994), (Yankelevich et al., 2019).  
 
2.1.4 
Targeting CD47 as a Macrophage Checkpoint 
 
Macrophage phagocytosis of cells is regulated by a balance of inhibitory and activating receptors. CD47 is a cell surface 
protein that functions as a regulator of phagocytosis by cells of the innate immune system. CD47 binds the SIRP-alpha 
receptor on phagocytes, delivering an inhibitory signal (Jaiswal et al., 2009). In this way, CD47 functions as a “don’t eat 
me” signal. Macrophages also recognize calreticulin, which is a pro-phagocytic or “eat me” signal expressed by cells slated 
for removal by the immune system (Chao, Alizadeh, et al., 2010). 
 
Anti-CD47 antibodies bind CD47 and block its interaction with SIRP-alpha. This results in blockade of the “don’t eat me” 
signal, pushing the macrophage balance towards phagocytosis and elimination of cancer cells. Most normal cells do not 
express calreticulin under normal conditions.  Thus, even though CD47 is widely expressed, normal cells are largely 
unaffected by the CD47 antibody (Chao, Alizadeh, et al., 2010).  
 
2.1.5 
Targeting macrophage checkpoints in children 
 
For cancers with high mutational burdens, such as melanoma, non-small cell lung cancer and colorectal cancers with 
microsatellite instability, blockade of PD-1, a T cell inhibitory signal, is often sufficient to unleash naturally acquired 
antitumor immunity (Gubin, Artyomov, Mardis, & Schreiber, 2015); (Rizvi et al., 2015). However, many pediatric cancers 
have a low mutational burden and are not sufficiently immunogenic to drive clinically significant antitumor immunity 
following checkpoint blockade. Sarcomas, in general, have relatively low mutational burdens and thus far responses to 
checkpoint blockade have been disappointing. Osteosarcoma, despite its deregulated genome, falls into the category of a 
cancer with an intermediate mutational burden and thus far, significant responses have not been observed following 
treatment with either ipilimumab (Merchant et al., 2016) or PD-1 blockade (K. L. Davis et al., 2020). Similarly, 
neuroblastoma manifests a relatively low number of genetic mutations (Pugh et al., 2013) and objective responses have not 
been observed following PD-1 blockade (R. J. Davis et al., 2017). 
 
While single agent T cell checkpoint inhibition may not represent a successful therapeutic approach in pediatric cancer (K. 
L. Davis et al., 2020), other groups have focused on macrophages as immune effectors in pediatric cancers. Studies have 
demonstrated that pediatric cancers are heavily infiltrated by macrophages (Vakkila, Jaffe, Michelow, & Lotze, 2006). A 
recently published study demonstrated remarkable activity of Hu-5F9 in preclinical models of pediatric brain tumors 

                              
 
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(Gholamin et al., 2017). Given the large numbers of macrophages that infiltrate sarcomas and neuroblastoma, this could 
represent a promising approach. 
 
2.1.6 
Hu5F9-G4 (magrolimab)  
 
Hu5F9-G4 (magrolimab) is a first-in-class anticancer therapeutic agent targeting the cluster of differentiation (CD) 47 signal 
regulatory protein alpha (SIRPα) axis (J. Liu et al., 2015), (Huang, Ma, Gao, & Yao, 2017). Hu5F9-G4 (magrolimab) is a 
recombinant humanized anti-CD47 monoclonal antibody of the IgG4 kappa isotype containing a Ser-Pro (S-P) substitution 
in the hinge region (position 228) of the heavy chain to reduce fragment antigen-binding (Fab) arm exchange (X. Liu et al., 
2015).  Hu5F9-G4 (magrolimab) binds to human CD47 on target malignant cells, blocks the anti-phagocytic signal to 
macrophages, enhances tumor cell phagocytosis, and elicits an anti-tumor T-cell response (Liu, Kwon, Li, & Fu, 2017), 
(Huang et al., 2017). 
 
Hu5F9-G4 (magrolimab) blocks the interaction of CD47 with its ligands and enables phagocytosis of human cancer cells 
(J. Liu et al., 2015).  The activity of Hu5F9-G4 (magrolimab) is primarily dependent on blocking CD47 binding to SIRPα 
and not on the recruitment of fragment crystallizable (Fc)-dependent effector functions.  Most normal cells lack expression 
of pro-phagocytic signals and are unaffected by Hu5F9-G4 binding to CD47 (Feng et al., 2015).  However, blockade of 
CD47 in tumors can enhance macrophage phagocytosis of cancer cells, and in preclinical studies, this results in a profound 
antitumor effect against solid tumors and hematological malignancies (J. Liu et al., 2015), (Chan et al., 2009).   
 
CD47 is widely expressed and has been identified as a key molecule mediating cancer cell evasion of phagocytosis by the 
innate immune system (J. Liu et al., 2015).  It provides an anti-phagocytic signal by binding to the N-terminus of SIRPα on 
immune cells and suppresses phagocytosis (Huang et al., 2017).  Hematopoietic stem cells transiently upregulate CD47 
expression to escape phagocytosis by macrophages before and during mobilization (Jaiswal et al., 2009).  The pathological 
role of CD47 is commonly responsible for the escape of malignant cancer cells from immune-surveillance. CD47 expression 
is increased on the surface of cancer cells from many diverse human tumor types including head and neck cancer, melanoma, 
breast, lung, ovarian, pancreatic, colon, bladder, prostate, leiomyosarcoma, glioblastoma, medulloblastoma, glioma, 
lymphoma, leukemia, and multiple myeloma (Chan et al., 2009), (Jaiswal et al., 2009), (Majeti et al., 2009), (Chao, 
Alizadeh, et al., 2010), (Chao, Jaiswal, et al., 2010), (Chao, Majeti, & Weissman, 2011), (Krampitz et al., 2016), (Edris et 
al., 2012), (Gholamin et al., 2017), (Weiskopf et al., 2016).  CD47 overexpression has been associated with poor prognosis 
in leukemia, non-Hodgkin lymphoma (NHL), bladder cancer, breast cancer, and other cancers (Huang et al., 2017), (Majeti 
et al., 2009), (Chao, Alizadeh, et al., 2010), (Chan et al., 2009), (Willingham et al., 2012).  Furthermore, elevated CD47 
messenger RNA (mRNA) expression correlates with a worse overall survival for multiple types of cancer (Willingham et 
al., 2012).  In murine xenograft studies, CD47-blocking antibodies can inhibit human cancer growth and metastasis by 
enabling the phagocytosis of cancer stem cells (CSCs) from various hematological malignancies and solid tumors.  CD47-
blocking antibodies have been shown to exhibit potent synergy with tumor-specific monoclonal antibodies, such as 
rituximab, cetuximab, and trastuzumab (Chao, Alizadeh, et al., 2010), (Weiskopf et al., 2013).   
 
Hu5F9-G4 (magrolimab) has demonstrated antitumor activity in breast, ovarian, brain, and bladder cancers, acute myeloid 
leukemia (AML), NHL, and other malignancies in preclinical studies (Chan et al., 2009), (Gholamin et al., 2017), (J. Liu et 
al., 2015), (Sikic et al., 2019), (Willingham et al., 2012).   
 
Mechanism of Action 
 
Hu5F9-G4 (magrolimab) is an anti-CD47 monoclonal antibody that disrupts the CD47/SIRPα interaction to induce 
macrophage-mediated phagocytosis (J. Liu et al., 2015).  Hu5F9-G4 (magrolimab) selectively binds to CD47 on tumor cells 
and prevents it from binding to SIRPα.  This inhibits CD47/SIRP signaling, causing the activation of macrophages which 
in the presence of additional prophagocytic signals, such as calreticulin can initiate specific tumor cell phagocytosis (Chao, 
Jaiswal, et al., 2010). Inhibiting CD47 signaling can also initiate an anti-tumor T-lymphocyte immune response and T-cell-

                              
 
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mediated killing (X. Liu et al., 2015). 
 
Summary of Nonclinical Experience 
 
The therapeutic effect of Hu5F9-G4 (magrolimab) was evaluated in human AML xenograft models in vivo with two 
independent primary patient samples (SU028 and SU048) (Investigator’s Brochure, 2019). Therapy was initiated with daily 
intraperitoneal (IP) injection of either control mouse IgG or 100 mcg of Hu5F9-G4 (magrolimab). The therapeutic response 
was monitored by analyzing the burden of AML cells in repeated bone marrow aspirates. Daily doses of 100 mcg of Hu5F9-
G4 (magrolimab) over 2 weeks cleared AML in the bone marrow of all mice at the end of treatment with recovery of normal 
hematopoiesis in the bone marrow, leading to a major survival benefit compared to control.    
The pharmacokinetics (PK) and toxicokinetics (Angelo et al., 2014) of Hu5F9-G4 (magrolimab) were studied in single- and 
repeat-dose (non-Good Laboratory Practice [GLP] and GLP) studies in the cynomolgus monkey and an 8-week pivotal 
toxicology study (Investigator’s Brochure, 2019). Hu5F9-G4 (magrolimab) has nonlinear PK with a varied half-life (t1/2), 
ranging from approximately 5 to 250 hours following single and multiple doses. The volume of distribution approximated 
monkey serum volume, as expected for a monoclonal antibody. The t1/2 appears to increase and clearance appears to decrease 
with increasing dose and with repeated dosing, suggesting saturation of target-mediated CL through the endogenous CD47 
cellular sink.  
 
Summary of Clinical Experience 
 
As of July 24, 2019, 401 patients have received Hu5F9-G4 (magrolimab) as monotherapy and in combination in six 
company sponsored clinical trials (SCI-CD47-001, SCI-CD47-002, 5F9003, 5F9004, 5F9005, and 5F9006) (Investigator’s 
Brochure, 2019). The two monotherapy studies include Study SCI-CD47-001, a phase 1 study in advanced solid tumor and 
lymphoma patients and Study SCI-CD47-002, a phase 1 study in relapsed/refractory (R/R) AML patients. The four 
combination studies include Study 5F9003, a phase 1b/2 of Hu5F9-G4 (magrolimab) with rituximab in NHL patients; Study 
5F9004, a phase 1b/2 of Hu5F9-G4 (magrolimab) with cetuximab in solid tumor and colorectal cancer (CRC) patients; 
Study 5F9005, a phase 1b study of Hu5F9-G4 (magrolimab) with azacitidine in AML and myelodysplastic syndrome (MDS) 
patients; and Study 5F9006, a phase 1b study of Hu5F9-G4 (magrolimab) with avelumab in solid tumor and ovarian cancer 
patients. 
 
Clinical Pharmacokinetics (PK) 
 
The PK data are available from 58 patients in the first in human (FIH) study, Study SCI-CD47-001 (Investigator’s Brochure, 
2019). Hu5F9-G4 (magrolimab) was administered at a dose range of .01 mg/kg to 30 mg/kg. The area under the 
concentration-time curve (Sikic et al., 2019) and maximum plasma concentration (Cmax) show greater than dose-proportional 
increases at doses ≤10 mg/kg and dose-proportional changes at 10 to 30 mg/kg. After priming dose of 1 mg/kg, a geometric 
mean Cmax of 0.682 mcg/mL (mg/L) was observed. After the second dose of 1 mg/kg, the geometric mean Cmax was 
approximately 10-fold higher at 5.83 mcg/mL. On continuous dosing, the geometric mean Cmax increased by another 2-fold 
to approximately 10 mcg/mL. The increase after the second dose was consistent with multiple dose accumulation.  This 
suggests time-dependent PK at 1 mg/kg between the first and the second doses. Due to the small number of patients, this 
phenomenon could not be characterized at other doses. The mean terminal t1/2 derived from the PK parameters was 
approximately 2 weeks at doses ≥10 mg/kg weekly. The PK of Hu5F9-G4 (magrolimab) is similar to other humanized 
monoclonal antibodies targeted towards cell-surface receptors. After multiple weekly doses ≥10 mg/kg, the CD47 antigen 
sink is fully saturated. 
 
The rate of anti-drug antibody (ADA) occurrence was low (10%) and typical for a humanized antibody (Investigator’s 
Brochure, 2019). Comparison of the PK of the ADA-positive and ADA-negative patients indicated that there was no impact 
of ADA occurrence on PK. There was no clear correlation between ADA occurrence and safety events. 
 

                              
 
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Clinical Safety Summary 
 
As of July 24, 2019, 401 (324 solid tumor/lymphoma and 77 AML/MDS patients) patients have received at least one dose 
of Hu5F9-G4 (magrolimab) as monotherapy or in combination (Investigator’s Brochure, 2019). Patients reported anemia 
(35.9%), fatigue (31.9%), headache (30.7%), infusion-related reaction (IRR) (25.7%), pyrexia (22.9%), chills (21.4%), 
nausea (19.5%), hemagglutination (14.5%), and vomiting (11.0%) as the most common treatment-related adverse events 
(AEs).  
 
A total of 397 serious adverse events (SAEs) have been reported in patients across all six clinical studies (Investigator’s 
Brochure, 2019). The most commonly reported SAEs include febrile neutropenia (40 events), IRRs (23 events), malignant 
neoplasm progression (20 events), small intestinal obstruction (17 events), pneumonia (16 events), anemia (15 events), and 
pyrexia (14 events).  Only three of the febrile neutropenia SAEs were considered related to Hu5F9-G4 (magrolimab) and 
none were reported in Studies 5F9004 and 5F9006, which enrolled only solid tumor patients. Twenty-one IRRs were 
considered related to Hu5F9-G4 (magrolimab), one was attributed to cetuximab only, and one was attributed to rituximab 
only. 
 
Of the 397 SAEs, 86 were considered related to Hu5F9-G4 (magrolimab) (Investigator’s Brochure, 2019). The most 
frequently reported serious adverse reactions (SARs) included IRR (21 events), anemia (11 events), pyrexia (7 events), and 
thrombocytopenia (4 events). Anemia and IRR have been identified as risks associated with Hu5F9-G4 (magrolimab), and 
four of the seven pyrexia SARs occurred within the 24 hours following a Hu5F9-G4 (magrolimab) infusion and could, 
therefore, be considered part of an IRR. No maximum tolerated dose (MTD) has been determined as monotherapy or in 
combination. No deaths have been attributed to Hu5F9-G4 (magrolimab) administration. 
 
The recommended phase 2 dose (RP2D) for solid tumor and lymphoma patients is 1 mg/kg (priming) followed by 30 mg/kg 
once every week for the first two cycles (28 days/cycle), followed by a dose of 30 mg/kg every 2 weeks (Investigator’s 
Brochure, 2019). In MDS and AML patients, the RP2D is 1 mg/kg priming on Days 1 and 4 followed by 15 mg/kg on day 
8 and 11 and then 30 mg/kg on days 15, and 22. Weekly doses are continued in Cycle 2 and then in Cycle 3 and beyond 30 
mg/kg every 2 weeks. All cycles are 28 days long. 
 
If patients have completed at least 1 cycle of dosing but have a treatment delay of greater than 4 weeks, then re-priming 
with the Cycle 1 doses and schedules should be instituted upon starting retreatment. Treatment interruptions of less than 4 
weeks can resume the treatment schedule without re-priming. 
 
Clinical Efficacy Summary 
 
In the FIH study, Study SCI-CD47-001, 62 solid tumor and lymphoma patients received Hu5F9-G4 (magrolimab) as 
monotherapy and were evaluable for efficacy (Investigator’s Brochure, 2019). Two of these patients had refractory diffuse 
large B-cell lymphoma (DLBCL) (Sikic et al., 2019). An additional 10 patients were treated in the cutaneous T-cell 
lymphoma (CTCL) cohort. In the dose-escalation cohorts, 13 treated patients had a diagnosis of ovarian or fallopian tube 
cancers. Two of these patients, both heavily pretreated and who received 20 mg/kg Hu5F9-G4 (magrolimab), had confirmed 
partial responses (PRs) with 50% and 44% reduction in tumor measurements. These patients were on treatment for 5.2 and 
9.2 months before progressing and they had received more than six prior lines of systemic therapy. No objective responses 
were observed in other patients.  In the dose escalation cohort, two patients with refractory DLBCL were treated with 
Hu5F9-G4 (magrolimab) monotherapy. No objective responses were observed; however, one patient had a mixed response 
(significant decrease in size of multiple tumor lesions, with increase size in others). 
 
For the CTCL patients, 10 patients were treated with Hu5F9-G4 (magrolimab) monotherapy at doses of 20 or 30 mg/kg in 
Study SCI-CD47-001, and response data are available for 8 CTCL patients (Investigator’s Brochure, 2019). No objective 
responses were observed; however, six patients had stable disease (SD), and two patients had disease progression (PD) as 

                              
 
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their best response. 
 
As of May 2019, Studies SCI-CD47-002 and 5F9005 evaluated efficacy in AML and MDS patients who received Hu5F9-
G4 (magrolimab) as monotherapy and in combination with azacytidine (Investigator’s Brochure, 2019). Twenty patients 
(all AML) were treated in Study SCI-CD47-002 study, and 57 patients (10 R/R AML and MDS, 46 treatment-naïve and 
unfit for standard induction therapy [TN/U] AML, and 1 rollover cohort) were treated in the Study 5F9005.  In Study SCI-
CD47-002, 58% of evaluable patients had a reduction in bone marrow blasts, but no objective responses were observed. 
Two of 18 evaluable patients with long-term stable disease (SD) had marked reductions in bone marrow cellularity, with 1 
remaining on treatment for greater than 11 months. One of these patients had a decrease in bone marrow blast count >50% 
and had a significant increase in T-cell infiltrate in the bone marrow; this patient was on therapy for 11.8 months.  In the 
monotherapy portion of Study 5F9005, the objective response rate (ORR) was 10% with one AML patient achieving a 
response of morphologic leukemia-free state.  In the combination portion of Study 5F9005, 25 patients were evaluable for 
efficacy.  In AML, 64% of patients achieved an objective response, including 55% with complete response (CR) + PR.  
Bone marrow blast reduction was observed in all but one patient on the Hu5F9-G4 (magrolimab) plus azacitidine 
combination. Hu5F9-G4 (magrolimab) in combination with azacytidine induced high ORRs in newly diagnosed AML 
patients who are ineligible for induction chemotherapy and newly diagnosed MDS patients who are intermediate to very 
high risk by Revised International Prognostic Scoring System (IPSS-R). 
 
In Study 5F9003, NHL patients received Hu5F9-G4 (magrolimab) in combination with rituximab (Investigator’s Brochure, 
2019). Efficacy was evaluated in a total of 97 patients, including 59 DLBCL patients, 35 follicular lymphoma (FL) patients, 
and 3 marginal zone lymphoma (MZL) patients. The overall ORR for all patients who received at least one dose of Hu5F9-
G4 (magrolimab) and had at least one post treatment response assessment was 45%, with 19% achieving a best response of 
CR.  In patients with DLBCL, the ORR was 36%, with 15% achieving a CR.  In FL and MZL, the ORR was 61%, with 
24% achieving CR.  Median time to response (TTR) was 1.7 months (range 1.6 to 6.6 months). In Phase 1b of the study, 
the median duration of response (Willingham et al.) was not reached for either DLBCL or FL patients with a median follow-
up of 13.8 and 21 months, respectively. 
 
2.1.7 
Dinutuximab 
 
Dinutuximab is a mouse-human chimeric monoclonal IgG1 antibody recognizing the disialoganglioside (GD2), a cell 
surface glycolipid that is expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including the 
central nervous system and peripheral nerves. Dinutuximab binds to cell surface GD2 and induces cell lysis of 
GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent 
cytotoxicity (CDC).  
 
Dinutuximab in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 
13-cis-retinoic acid (RA) was approved by the FDA in March 2015 for treatment of high-risk neuroblastoma in pediatric 
patients who achieved at least a partial response to prior therapy. Dinutuximab’s unique adverse event profile includes 
neuropathic pain and electrolyte abnormalities, as well as the usual monoclonal antibody events of infusion reactions, pain, 
pyrexia, and myelosuppression. Given the rare, yet severe peripheral sensory neuropathy that dinutuximab can elicit, the 
package insert contains black box labeling outlining the risk of neuropathy. Preclinical studies have demonstrated that the 
neuropathic pain associated with dinutuximab is mediated by GD2 binding on the nerve sheath surface. 
 
Dinutuximab has been safely administered in combination with other standard therapies (Mody et al., 2017). COG sponsored 
a randomized trial to enhance the results of salvage chemotherapy for recurrent neuroblastoma which led to an increasingly 
frequent use of irinotecan and temozolomide and GM-CSF in combination with dinutuximab. A phase 1 trial 
(NCT01711554) combining ch14.18 with lenalidomide and 13-cis-RA is showing promising results in children and young 
adults with recurrent, refractory, or persistent neuroblastoma (Keyel & Reynolds, 2018). 
 

                              
 
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2.2 
Rationale for Combining GD2 and CD47 in Neuroblastoma and Osteosarcoma 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Given the success of anti-GD2 antibodies in neuroblastoma, we investigated whether these agents could synergize with 
CD47 blockade. Using localized and metastatic models of neuroblastoma, we found that combination of anti-GD2 and anti-
CD47 antibodies led to tumor clearance and prolonged survival, while monotherapy had limited activity (Figure 3A-D). To 
assess the efficacy of this combination therapy in osteosarcoma, we used the MG63.3 cell line. Neither single agent anti-
GD2 nor anti-CD47 had any effect on tumor growth kinetics in an orthotopic xenograft model, but the combination of the 
two agents prevented tumor growth and resulted in enhanced survival ( 
 
 
 
Figure 4A-B). Additionally, in a metastatic model of osteosarcoma that mimics the clinical situation of patients with 
pulmonary micrometastatic disease ( 
 
 
 
Figure 4C), the combination of anti-GD2 and anti-CD47 antibodies prevented the development of lung metastasis, while 
in all other groups, mice developed a high burden of metastatic disease ( 
 
 
Day 4
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Figure 3: Anti-GD2 and anti-CD47 antibodies result in synergistic activity and prolonged tumor clearance 
in xenograft models of neuroblastoma 
Figure 3: Anti-GD2 and anti-CD47 antibodies result in synergistic activity and prolonged tumor 
clearance in xenograft models of neuroblastoma.  (A) KCNR was implanted into the kidney capsule of NSG 
mice prior to treating with anti-GD2, anti-CD47, or anti-GD2 and anti-CD47 antibodies.  Tumor clearance was 
seen only in mice receiving anti-GD2 and anti-CD47, (B)resulting in prolonged survival. (C) NSG mice were 
intravenously injected with CHLA255 prior to treating with anti-GD2, anti-CD47, or anti-GD2 and anti-CD47 
antibodies.  Tumor clearance was only observed in mice receiving anti-GD2 and anti-CD47, (D) resulting in 
prolonged survival. 

                              
 
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Figure 4D). Further preclinical studies (data not shown) have demonstrated that GD2 itself may be a “Don’t Eat Me” signal 
that inhibits macrophage phagocytosis and that GD2 crosslinking drives upregulation of calreticulin, marking tumor cells 
for removal by macrophages. Therefore, anti-GD2 and anti-CD47 antibodies are a rational combination that can result in 
significant anti-tumor activity in patients with neuroblastoma and osteosarcoma. 
 
 
 
 
 
Figure 4: Anti-GD2 and anti-CD47 antibodies result in synergistic activity in xenograft models of 
osteosarcoma 
 
 
 
 
 
 
 
 
2.3 
Correlative Studies Background 
 
2.3.1 Explore biomarkers of response and resistance including genomic (CD47 expression, FcR polymorphisms 
and KiR phenotype) and immunologic (dinutuximab HACA, magrolimab ADA, peripheral immune 
subsets, and circulating cytokines) 
 
CD47 expression is ubiquitous on most human tissues. It is currently unknown whether expression (qualitative or 
Figure 4: Anti-GD2 and anti-CD47 antibodies result in synergistic activity in xenograft models of 
osteosarcoma. (A) MG63.3 was implanted into the tibia of NSG mice three days prior to treating with anti-GD2, 
anti-CD47, or anti-GD2 and anti-CD47 antibodies. A delay in tumor growth was seen only in mice receiving anti-
GD2 and anti-CD47 combined, (B) resulting in prolonged survival. (C) MG63.3 was implanted into the tibia of NSG 
mice. After four weeks, the primary tumor was amputated with the hind limb. Mice were treated with anti-GD2, anti-
CD47, or anti-GD2 and anti-CD47 antibodies. (D) A reduction in the number and size of pulmonary metastasis was 
seen in mice in the combination group. 

                              
 
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quantitative) of CD47 on tumor cells or surrounding cells in the tumor microenvironment is predictive of response to CD47 
blockade. CD47 expression will be assessed by immunohistochemistry using a validated antibody on tumor tissue, where 
available, including archival samples, tumor biopsy samples, and bone marrow samples (when involved by disease). 
 
Genetic polymorphisms in the Fc Receptor (FcR) and Killer Cell Immunoglobulin-Like Receptor (KIR) phenotype have 
been associated with variable responses to antibody-based therapies, including anti-GD2 in neuroblastoma (Erbe et al., 
2018; Siebert et al., 2016). Macrophage activity (as well as NK cell activity) are targets of anti-CD47 therapy, and these 
receptors may make a patient more or less likely to respond to anti-CD47 and/or anti-GD2. 
 
As dinutuximab is a chimeric antibody consisting of murine variable regions fused to a human Fc region, some patients 
develop antibodies capable of recognizing and neutralizing dinutuximab (human anti-chimera antibodies, HACA). It is 
expected that many neuroblastoma patients on this trial will have been previously treated with dinutuximab. We will 
therefore measure baseline and on-treatment HACA as has been previously reported in the literature (Angelo et al., 2014). 
 
Anti-CD47 can unleash the innate immune system through activation of macrophages and NK cells, but has also been shown 
to generate/unleash a native T cell response (Tseng et al., 2013). Therefore, patient blood and bone marrow (when obtained 
for disease evaluation) will be subjected to immune phenotyping to look for immune activation/response using validated 
CyTOF panels. Additionally, patient plasma will be collected during therapy to look for changes in circulating cytokines 
using the Luminex platform. 
 
2.3.2 
Explore biomarkers of response in the tumor microenvironment through MIBI on resected tissue or archival tissues 
including comparison of pre- and post- treatment tumor tissues from patients undergoing staged resection of 
pulmonary osteosarcoma 
 
Despite frequent metastasectomy performed in osteosarcoma, there is a dearth of information on the immune 
microenvironment in lung metastases in osteosarcoma. By treating patients undergoing staged metastasectomy between the 
two resections, we will obtain pre- and post-treatment biopsies, which are rarely obtained on pediatric trials. This will allow 
us to compare the tumor immune microenvironment before and after treatment with anti-GD2/anti-CD47. We will evaluate 
these tumors using a validated Multiplexed ion beam imaging (MIBI) panel to explore the tumor immune microenvironment 
(Angelo et al., 2014). 
 
3 
PATIENT ELIGIBILITY 
 
3.1 
Eligibility Inclusion Criteria  
 
Important note: The eligibility criteria listed below are interpreted literally and cannot be waived. All clinical 
and laboratory data required for determining eligibility of a patient enrolled on this trial must be available 
in the patient’s medical or research record which will serve as the source document for verification at the 
time of audit. 
 
3.1.1 
Patients must have a history of histologically or cytologically confirmed NBL or osteosarcoma. 
 
 
3.1.2 
Diagnosis 
Patients must have: 
• 
Relapsed/Refractory High-Risk Neuroblastoma (NBL) (defined as disease recurrence after completion of 

                              
 
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therapy, progressive disease on therapy, or refractory disease during induction therapy) 
 or  
• 
Relapsed Osteosarcoma (relapsed after frontline therapy and/or there must not be any potentially curative 
treatment options available at the time of enrollment) 
 
3.1.3 
Disease Status 
Patients must have measurable or evaluable disease as follows: 
 
3.1.3.1 
Cohort B1: Confirmed neuroblastoma: measurable NBL/ganglioneuroblastoma (defined as those lesions 
that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm 
with cross sectional imaging (CT scan or MRI), or ≥ 10 mm with calipers by clinical exam). Chest x-ray 
cannot be used to determine eligibility. Lesions must be MIBG positive, PET avid (if patient has a history 
MIBG negative disease) or biopsy proven NBL/ganglioneuroblastoma. 
3.1.3.2 
Cohort B2: Evaluable NBL (MIBG and/or bone marrow disease only) 
3.1.3.3 
Cohort B3: Measurable osteosarcoma (defined as those lesions that can be accurately measured in at least 
one dimension (longest diameter to be recorded) as ≥10 mm (≥1 cm) with cross sectional imaging (CT 
scan, MRI, or calipers by clinical exam). Chest x-ray cannot be used to determine eligibility. 
3.1.3.4 
Cohort B4: Patients with relapsed resectable pulmonary osteosarcoma who are scheduled for a surgical 
resection.  
 
Note: Subjects will not have measurable disease due to recently resected pulmonary metastases. Investigational 
therapy must begin within three weeks of resection. Staged resections are permissible; investigational therapy 
will be administered in between resections. Patients should receive one cycle of investigational therapy in between 
resections but can receive additional cycles to accommodate the most appropriate surgical schedule as determined 
by the treating physicians. Every effort will be made to have at least half of this cohort (five of ten patients) be 
those requiring a staged resection. 
 
3.1.4 
Prior Therapy: 
• 
There is no limit to the number of prior treatment regimens. Patients must have fully recovered from the acute 
toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to initiation of study treatment. 
Acute toxicity of any previous therapy must have resolved to grade 1 or less or stabilized, unless specified 
elsewhere.  
o Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy 
within 3 weeks of initiation of study treatment (6 weeks if prior nitrosourea). 
o Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with 
a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.  
o At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, 
tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen.  
o At least 4 weeks must have elapsed since prior therapy with 131I-MIBG. 
o Monoclonal antibodies: At least 3 weeks must have elapsed since prior therapy that included a 
monoclonal antibody. Patients who have received prior therapy with GD2 antibodies, regardless of 
response to therapy, will be eligible. 
o At least 7 days must have elapsed since the last pharmacologic dose of systemic corticosteroids 
 
3.1.5 
Age: 
• 
Arm A: Age ≥2 or < 18 years of age. 
• 
Arm B: Age ≥2 or ≤ 35 years of age. 

                              
 
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3.1.6 
Performance Status: ECOG performance status ≤2; Subjects > 16 years of age: Karnofsky ≥ 50%; Subjects ≤ 16 
years of age: Lansky scale ≥50% (see APPENDIX A: PERFORMANCE STATUS CRITERIA) 
 
3.1.7 
Patients must have adequate organ and marrow function as defined below: (supportive care is allowed per 
institutional standards, i.e., filgrastim, transfusion, etc.) 
− 
absolute neutrophil count 
 
≥ 1,000/mcL 
− 
hemoglobin  
 
≥ 9.5 g/dL, transfusion support acceptable 
− 
platelets 
 
 
≥ 100,000/mcL, independent of transfusions 
− 
total bilirubin 
 
≤ 1.5 X institutional upper limit of normal (ULN) for age (sum of 
conjugated and unconjugated) 
− 
AST(SGOT)/ALT(SGPT) 
 
≤ 5 × institutional ULN 
− 
creatinine  
 
≤ institutional ULN 
OR 
− 
glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2  
 
3.1.8 
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral 
load within 6 months are eligible for this trial. 
 
3.1.9 
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable 
on suppressive therapy, if indicated. 
 
3.1.10 Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with 
HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load 
 
3.1.11 Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to 
interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. 
 
3.1.12 Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, 
should have a clinical risk assessment of cardiac function using the New York Heart Association Functional 
Classification. To be eligible for this trial, patients should be class 2B or better. 
 
3.1.13 Female patients of childbearing potential must not be nursing or planning to be pregnant and must have a negative 
urine or serum pregnancy test within 30 days before enrollment and within 72 hours before the first administration 
of study treatment.  
 
Note: Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are 
not considered to be of childbearing potential. 
 
3.1.14 The effects of Hu5F9-G4 (magrolimab) monoclonal antibody on the developing human fetus are unknown and 
dinutuximab is known to be teratogenic. For this reason, female patients of childbearing potential must be willing 
to use one highly effective method of contraception (hormonal or barrier method of birth control; abstinence) prior 
to study entry, during the study and continue for 4 months after the last dose of study treatment. Should a woman 
become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform 
her treating physician immediately. 
 
Male patients who are sexually active with a woman of childbearing potential (WOCBP) and who have not had 
vasectomies must be willing to use a barrier method of contraception (condom plus spermicidal gel) and refrain 
from sperm donation during the study and for 4 months after the last dose of study treatment. If the partner is 

                              
 
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pregnant, male patients must use barrier method contraception (condom) during the study and for 4 months after 
the last dose of study treatment to prevent fetal exposure to study treatment. 
 
3.1.15 All patients and/or their parents or legally authorized representatives must have the ability to understand and the 
willingness to sign a written informed consent. Assent, where appropriate, will be obtained according to local 
institutional policy.  
 
3.1.16 Cardiac Function: Cardiac ejection fraction ≥ 45% or shortening fraction ≥ 28%, no evidence of physiologically 
significant pericardial effusion as determined by an ECHO, MUGA or Cardiac MRI. No clinically significant ECG 
findings that in the judgment of the treating investigator would present a contraindication for treatment. 
 
 
3.2 
Exclusion Criteria 
 
3.2.1 
History of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-GD2 
monoclonal antibody (dinutuximab) or Hu5F9-G4 (magrolimab) monoclonal antibody or other agents used in this 
study. 
 
3.2.2 
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive 
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit 
compliance with study requirements. 
 
3.2.3 
Patients who are receiving any other investigational agents. 
 
3.2.4 
Pregnant women are excluded from this study because Hu5F9-G4 (magrolimab)is a monoclonal antibody on the 
developing human fetus are unknown and dinutuximab may cause fetal harm. Because there is an unknown but 
potential risk for adverse events in nursing infants secondary to treatment of the mother with Hu5F9-G4 
(magrolimab) or dinutuximab, breastfeeding should be discontinued if the mother is treated with Hu5F9-G4 
(magrolimab) or dinutuximab.   
 
3.2.5 
Patients who have received prior treatment with CD47 or SIRPα-targeting agents.  
 
3.2.6 
Patients with red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBCs 
transfused during the 4-week period prior to screening. RBC transfusions are permitted during the screening period 
and prior to enrollment. 
 
3.2.7 
Patients with known inherited or acquired bleeding disorders are not eligible 
 
3.2.8 
Patients with prior hemolytic anemia or Evans Syndrome in the last 3 months. 
 
3.2.9 
Patients with significant medical diseases that would worsen the risk-benefit ratio of participating in this study. This 
includes but is not limited to acute myocardial infarction within the last 6 months, unstable angina, significant acute 
or chronic infections, or severely immunocompromised state. 
 
3.2.10 Patients on the following medications at the time of study treatment initiation: 
• 
Immunotherapy or immunosuppressive drugs (e.g. chemotherapy or systemic corticosteroids) EXCEPT for the 
following:  
o The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent 
dose of an alternative corticosteroid) as premedication for blood product administration in order to 

                              
 
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avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment 
of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal 
insufficiency. 
• 
Growth factors (granulocyte colony stimulating factor or granulocyte macrophage colony stimulating factor) 
EXCEPT for erythropoietin and darbepoietin alpha. 
• 
Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known to potentially interfere 
with major organ function (e.g. hypericin). 
 
3.2.11 Patients administered a live vaccine within 28 days prior to initiation of study treatment. 
 
3.2.12 Patients with active or previously treated central nervous system (CNS) metastasis. 
 
 
3.3 
Inclusion of Women and Minorities 
 
NIH policy requires that women and members of minority groups and their subpopulations be included in all NIH-supported 
biomedical and behavioral research projects involving NIH-defined clinical research unless a clear and compelling rationale 
and justification establishes to the satisfaction of the funding Institute & Center (IC) Director that inclusion is inappropriate 
with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances must be 
designated by the Director, NIH, upon the recommendation of an IC Director based on a compelling rationale and 
justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. 
Women of childbearing potential should not be routinely excluded from participation in clinical research.  Please see 
http://grants.nih.gov/grants/funding/phs398/phs398.pdf. 
 
Females ages 2 to 35 years of age will be included in this study. Any other age is outside the scope of this study. 
 
There is no discrimination for the inclusion and planned distribution of patients by gender, race, ethnicity for this study (see 
Section 9.3, Planned Enrollment Report).  
 
4 
REGISTRATION PROCEDURES 
 
4.1 
Investigator and Research Associate Registration with CTEP 
 
Food and Drug Administration (FDA) regulations require sponsors to select qualified investigators. National Cancer 
Institute (NCI) policy requires all individuals contributing to NCI-sponsored trials to register with their qualifications and 
credentials and to renew their registration annually. To register, all individuals must obtain a Cancer Therapy Evaluation 
Program (CTEP) Identity and Access Management (IAM) account at https://ctepcore.nci.nih.gov/iam. Investigators and 
clinical site staff who are significant contributors to research must register in the Registration and Credential Repository 
(RCR). The RCR is a self service online person registration application with electronic signature and document submission 
capability. .    
 
RCR utilizes five person registration types. 
• 
Investigator (IVR):  MD, DO, or international equivalent, 
• 
Non Physician Investigator (NPIVR):  advanced practice providers (e.g., NP or PA) or graduate level researchers 
(e.g., PhD), 
• 
Associate Plus (AP):  clinical site staff (e.g., RN or CRA) with data entry access to CTSU applications such as the 
Roster Update Management System [RUMS], OPEN, Rave, acting as a primary site contact, or with consenting 
privileges; 
• 
Associate (A):  other clinical site staff involved in the conduct of NCI-sponsored trials,  

                              
 
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• 
Associate Basic (AB):  individuals (e.g., pharmaceutical company employees) with limited access to NCI-supported 
systems. 
 
RCR requires the following documents outlined in Table 1: 
 
Table 1: RCR Required Documentation 
 
Documentation Required 
IVR 
NPIVR 
AP 
A 
AB 
Form FDA 1572 
 
 
 
Financial Disclosure Form 
 
 
 
 
NCI Biosketch (education, training, employment, 
license, and certification) 
 
 
 
 
Good Clinical Practice (GCP) Training 
 
 
 
 
Agent Shipment Form (if applicable) 
 
 
CV (optional) 
 
 
 
 
 
An active CTEP-IAM user account with a linked ID.me account (the latter required immediately for new CTEP-IAM 
accounts, and by July 1, 2023 for all users)  is required to participate in the NCI clinical trials supported by the Cancer Trials 
Support Unit (CTSU) and to access all CTEP and CTSU websites and applications.  In addition, IVRs and NPIVRs must 
list all clinical practice sites and Institutional Review Boards (IRBs) covering their practice sites on the FDA Form 1572 in 
RCR to allow the following: 
• 
Addition to a site roster;  
• 
Selection as the treating, consenting, treating, credit, or drug shipment investigator or consenting person in OPEN; 
• 
Ability to be named as the Site-Protocol Principal Investigator (PI) on the IRB approval; and 
• 
Assignment of the Clinical Investigator (CI) task on the Delegation of Tasks Log (DTL). 
 
In addition, all investigators acting as the Site-Protocol PI (investigator listed on the IRB approval), consenting/treating/drug 
shipment investigator in OPEN, or as the CI on the DTL must be rostered at the enrolling site with a participating 
organization. 
 
Additional information is located on the CTEP website at https://ctep.cancer.gov/investigatorResources/default.htm. For 
questions, please contact the RCR Help Desk by email at RCRHelpDesk@nih.gov. 
 
 
4.2 
CTSU Registration Procedures 
 
Permission to view and download this protocol and its supporting documents is restricted and is based on person and site 
roster assignment housed in the CTSU Regulatory Support System (RSS). 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU).  
 
4.2.1 
IRB Approval   
 
U.S. sites participating in the PEP-CTN network are required to use the NCI CIRB as of March 1, 2019.  Local IRB review 

                              
 
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will continue to be accepted for studies that are not reviewed by the CIRB, or if the study was previously open at the site 
under the local IRB. International sites should continue to submit Research Ethics Board (REB) approval to the CTSU 
Regulatory Office following country-specific regulations.  
 
Sites participating with the NCI CIRB must submit the Study Specific Worksheet (SSW) for Local Context to the CIRB 
using IRBManager to indicate their intent to open the study locally. The NCI CIRB’s approval of the SSW is automatically 
communicated to the CTSU Regulatory Office, but sites are required to contact the CTSU Regulatory Office at 
CTSURegPref@ctsu.coccg.org to establish site preferences for applying NCI CIRB approvals across their Signatory 
Network. Site preferences can be set at the network or protocol level.   
Questions about establishing site preferences can be addressed to the CTSU Regulatory Office by emailing the email address 
above or calling 1-888-651-CTSU (2878). 
 
Sites using their local IRB or REB must submit their approval to the CTSU Regulatory Office using the Regulatory 
Submission Portal located in the Regulatory section of the CTSU website. Acceptable documentation of local IRB/REB 
approval includes: 
• 
Local IRB documentation, 
• 
IRB-signed CTSU IRB Certification Form, and/or 
• 
Protocol of Human Subjects Assurance Identification/IRB Certification/Declaration of Exemption Form. 
 
In addition, the Site Principal Investigator (Site PI) (i.e., the investigator on the IRB/REB approval) must meet the following 
criteria for the site to be able to have an Approved status following to complete processing of the IRB/REB approval record: 
• 
Have an Active CTEP status; 
• 
Have an Active status at the site(s) on the IRB/REB approval (applies to US and Canadian sites only)and on at least 
one participating organization’s roster; 
• 
If using NCI CIRB, be active on the NCI CIRB roster under the applicable CIRB Signatory Institution(s) record;  
• 
Include the IRB number of the IRB providing approval in the Form FDA 1572 in RCR profiles; 
• 
Lists all sites on the IRB/REB approval as Practice Sites in Form FDA 1572 in the RCR profile; and 
• 
Have the appropriate CTEP registration type for the protocol. 
 
 
4.2.2 
Additional Requirements 
 
Additional site requirements to obtain an approved site registration status include: 
• 
An active Federal Wide Assurance (FWA) number; 
• 
An active roster affiliation with the Lead Protocol Organization (LPO) or a Participating Organization;  
• 
An active roster affiliation with the NCI CIRB roster under at least one CIRB Signatory Institution (US sites only); 
and 
• 
Compliance with all applicable protocol-specific requirements (PSRs). 
 
Note: Sites participating on the NCI CIRB initiative and accepting CIRB approval for the study are not required 
to submit separate IRB approval documentation to the CTSU Regulatory Office for initial, continuing or 
amendment review. 
 
4.2.3 
 Submitting Regulatory Documents 
 
Submit required forms and documents to the CTSU Regulatory Office using the Regulatory Submission Portal on 
the CTSU member’s website.  
 

                              
 
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To access the Regulatory Submission Portal, log in to the CTSU members’ website, go to the Regulatory section 
and select Regulatory Submission. 
 
Institutions with patients waiting that are unable to use the Regulatory Submission Portal should alert the CTSU 
Regulatory Office immediately by phone or email: 1-866-651-CTSU (2878), or CTSURegHelp@coccg.org in order 
to receive further instruction and support. 
 
4.2.4 
Delegation of Tasks Log (DTL) 
 
Each site must complete a protocol-specific Delegation of Tasks Log (DTL) using the DTL application in the Delegation 
Log section on the CTSU members’ website. The Clinical Investigator (CI) is required to review and electronically sign the 
DTL prior to the site receiving an approved site registration status and enrolling patients to the study. To maintain an 
approved site registration status the CI must re-sign the DTL at least annually and when a new version of the DTL is 
released; and to activate new task assignments requiring CI sign-off. Any individual at the enrolling site on a participating 
roster may initiate the site DTL. Once the DTL is submitted for CI approval, only the designated DTL Administrators or 
the CI may update the DTL. Instructions on completing the DTL are available in the Help Topics button in the DTL 
application and describe DTL task assignments, CI signature, and CTEP registration requirements, as well as include a 
Master Task List.. 
 
4.2.5 
Checking Your Site’s Registration Status 
Site registration status may be verified on the CTSU members’ website.  
• 
Click on Regulatory at the top of the screen; 
• 
Click on Site Registration; and 
• 
Enter the sites 5-character CTEP Institution Code and click on Go: 
o 
Additional filters are available to sort by Protocol, Registration Status, Protocol Status, 
and/or IRB Type. 
Note: The status shown only reflects institutional compliance with site registration requirements as outlined within the 
protocol. It does not reflect compliance with protocol requirements for individuals participating on the protocol or the 
enrolling investigator’s status with NCI or their affiliated networks. 
Requirements For PEP-CTN Site Registration 
IRB approval (For sites not participating via the NCI CIRB; local IRB documentation, an IRB signed CTSU IRB 
Certification Form, Protocol of Human Subjects Assurance Identification/IRB Certification, and/or Protocol Human Subjects 
Assurance Identification/IRB Certification/Declaration of Exemption Form 
 
4.3 
Patient Enrollment 
Investigators should refer to the COG website to determine if the study is currently open for accrual.  
 
 
4.3.1 
OPEN 
 
Patient enrollment for this study will be facilitated using the Slot Reservation System in conjunction with the 
registration system in Oncology Patient Enrollment Network (OPEN).  
Requirements for OPEN access: 
• 
A valid CTEP-IAM account and linked ID.me account (ID.me accounts are required for all newly created 

                              
 
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CTEP-IAM accounts and by July 1, 2023 for all users); 
• 
To perform enrollments or request slot reservations: Must be on an LPO roster, ETCTN corresponding roster, 
or participating organization roster with the role of Registrar. Registrars must hold a minimum of an  Associate Plus 
(AP) registration type; 
• 
If a Delegation of Tasks Log (DTL) is required for the study, the registrar) must hold the ‘OPEN Registrar’ task 
on the DTL for the site; and 
• 
Have an approved site registration for the protocol prior to patient enrollment. 
Access OPEN at https://open.ctsu.org or from the OPEN link on the CTSU members’ website. Further instructional 
information is in the OPEN section of the CTSU website at https://www.ctsu.org or at https://open.ctsu.org. For 
any additional questions, contact the CTSU Help Desk at 1-888-823-5923 or ctsucontact@westat.com. 
 
Prior to accessing OPEN, site staff should verify the following: 
• 
Patient has met all eligibility criteria within the protocol stated timeframes; and  
• 
All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act 
(HIPAA) authorization form (if applicable).  
 
Note: The OPEN system will provide the site with a printable confirmation of registration and treatment information. 
Please print this confirmation for your records. 
 
Access OPEN at https://open.ctsu.org or from the OPEN link on the CTSU members’ website. Further instructional 
information is in the OPEN section of the CTSU website at https://www.ctsu.org or https://open.ctsu.org. For any 
additional questions, contact the CTSU Help Desk at 1-888-823-5923 or ctsucontact@westat.com. 
 
 
4.3.2 
Patient Registration 
 
Prior to enrollment on study, patients must be assigned a COG patient ID number. This number is obtained via the 
COG Registry in the OPEN system once authorization for the release of protected health information (PHI) has 
been obtained.   
If you have problems with the registration, please refer to the online help. For additional help or information, please 
contact the CTSU Help Desk at 1-888-823-5923 or ctsucontact@westat.com. 
 
4.3.3 
Reservation and Contact Requirements 
Prior to enrolling a patient, a reservation must be made following the steps below and the Study Chair or Vice Chair 
notified. (The patient will need a COG patient ID number in order to obtain a reservation). Reservations may be 
obtained 24 hours a day through the Oncology Patient Enrollment Network (OPEN) system. Patients must be 
enrolled within 7 calendar days of making a reservation. 
 
If the study is active, a reservation can be made by following the steps below: 
 
1) Log in to https://open.ctsu.org/open/ using your CTEP IAM username and password.  
2) In order to make a reservation, the patient must have an OPEN patient number. Click on the ‘Slot Reservation’ 
tab to create an OPEN patient number, under ‘Patients’. 
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4) On the ‘Create Slot Reservation’ page, select the Protocol Number, enter the COG Patient ID, and choose the 
required stratum (if applicable) in order to obtain a reservation. 
 
Refer to the ‘Slot Reservation Site User Guide’ posted under the ‘Help’ tab in OPEN for detailed instructions: 
https://www.ctsu.org/open/Site_Resources/Training/Users_Manual/CTSU-OPEN-
SlotReservationSiteUserGuide.pdf  
 
4.4 
General Guidelines 
 
Patients may be enrolled on the study once all eligibility requirements for the study have been met. Patients who 
give informed consent for the protocol in order to undergo screening for eligibility are not considered enrolled and 
should not be enrolled until the screening is completed and they are determined to meet all eligibility criteria. 
 
Following enrollment, patients should begin protocol treatment within 7 calendar days. Issues that would cause 
treatment delays should be discussed with the Study Chair. Patients must not receive any protocol therapy prior 
to enrollment. 
 
4.4.1 Informed Consent/Assent 
The investigational nature and objectives of the trial, the procedures and treatments involved and their attendant risks 
and discomforts, and potential alternative therapies will be carefully explained to the patient or the patient’s parents 
or guardian if the patient is a child. All patients and/or their parents or legally authorized representatives must sign a 
written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines 
 
4.4.2 Screening Procedures  
Diagnostic or laboratory studies performed exclusively to determine eligibility for this trial must only be done after 
obtaining written informed consent. Documentation of the informed consent for screening will be maintained in the 
patient’s research chart. Studies or procedures that were performed for clinical indications (not exclusively to 
determine eligibility) may be used for baseline values even if the studies were done before informed consent was 
obtained. 
 
4.4.3 Eligibility Checklist  
Before the patient can be enrolled, the responsible institutional investigator must sign and date the completed 
eligibility checklist. A signed copy of the checklist will be uploaded into RAVE immediately following enrollment. 
 
4.4.4 Institutional Pathology Report  
Immediately following enrollment, the institutional pathology report for the diagnosis under which the patient is being 
enrolled must be uploaded into RAVE. The report must include the associated study number and COG patient 
registration and accession numbers. Personal identifiers, including the patient’s name and initials must be removed 
from the institutional pathology report prior to submission. 
 
 
 

                              
 
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5 
BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES 
 
Table 2: List of Biomarkers in Order of Priority 
 
Note for participating sites: See Table 3 for details on specimens to collect. The specimens tested are not always the same 
specimens that are submitted by the site, as processing of blood and tissue will occur at the EET Biobank prior to testing.  
 
Priority Biomarker 
Name 
Assay 
(CLIA: 
Y/N) 
Use 
in 
the 
Trial 
(Integral, Integrated, 
or Exploratory) AND 
Purpose 
Specimens 
Tested 
Collection Time Points Mandatory 
or Optional Assay 
Laboratory and 
Lab PI 
Tissue-based Biomarkers 
1 
MIBI 
for 
immune cell 
infiltration 
Multiple
xed ion 
beam 
imaging 
CLIA: N 
No 
Review 
Require
d 
Exploratory 
 
1)  Understand the 
baseline immune cell 
infiltration in archival 
samples of relapsed or 
refractory 
neuroblastoma 
and 
osteosarcoma 
 
2) 
Compare 
the 
immune 
cell 
infiltration before and 
after treatment with 
anti-CD47/anti-GD2 in 
patients with relapsed 
pulmonary 
osteosarcoma 
undergoing 
staged 
resections 
 
3) 
Compare 
the 
immune 
cell 
infiltration before and 
after treatment with 
anti CD47/anti-GD2 in 
patients with relapsed 
osteosarcoma 
or 
neuroblastoma 
undergoing 
optional 
biopsies 
FFPE 
tumor 
tissue 
1) Archival Tissue 
 
2) Pulmonary Metastases 
resected 
from 
staged 
resection at enrollment 
and then after one cycle 
of 
protocol 
therapy 
(cohort B4 only) 
 
3) 
Clinical 
biopsies 
obtained during therapy 
or at disease progression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1) Optional 
2) 
Mandatory 
(cohort 
B4 
only) 
3) Optional 
Angelo 
Laboratory, 
Department 
of 
Pathology, 
Stanford 
University 
Michael Angelo  
mangelo0@stanf
ord.edu 
 

                              
 
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Version Date: 02/02/2024 
 
 
Page 30 
 
 
Priority Biomarker 
Name 
Assay 
(CLIA: 
Y/N) 
Use 
in 
the 
Trial 
(Integral, Integrated, 
or Exploratory) AND 
Purpose 
Specimens 
Tested 
Collection Time Points Mandatory 
or Optional Assay 
Laboratory and 
Lab PI 
2 
CD47 
Expression 
Immuno
histoche
mistry 
CLIA: N 
No 
Review 
Require
d 
Exploratory 
Assess contribution of 
CD47 
to 
disease 
response 
Unstained 
slides from 
FFPE 
tumor 
tissue 
1) 
Archival 
Tissue 
 
2) 
Pulmonary 
Metastases 
resected 
from staged resection 
at enrollment and then 
after one cycle of 
protocol 
therapy 
(cohort B4 only) 
 
3) 
Clinical 
biopsies 
obtained 
during therapy or at 
relapse 
 
 
 
 
 
 
 
Optional 
Stanford 
Pathology 
3 
Sample 
Banking 
 
Sample banking for 
future study 
Frozen  
tumor 
tissue 
(when 
available) 
1) 
Available 
archival tissue 
 
2) 
Pulmonary 
Metastases 
resected 
from staged resection 
at enrollment and then 
after one cycle of 
protocol 
therapy 
(cohort B4 only) 
 
3) 
Clinical 
biopsies 
obtained 
during therapy or at 
disease progression 
 
Optional 
EET Biobank 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 31 
 
 
Priority Biomarker 
Name 
Assay 
(CLIA: 
Y/N) 
Use 
in 
the 
Trial 
(Integral, Integrated, 
or Exploratory) AND 
Purpose 
Specimens 
Tested 
Collection Time Points Mandatory 
or Optional Assay 
Laboratory and 
Lab PI 
4 
CyTOF for 
immune 
subsets 
Mass 
Cytomet
ry 
CLIA: N 
 
Exploratory 
To determine changes 
in 
the 
peripheral 
immune subsets as a 
result of treatment with 
anti-CD47 / anti-GD2 
Mononucle
ar 
cells 
from bone 
marrow in 
Sodium 
Heparin 
tube 
1) Baseline 
 
2) Disease 
restaging 
(cycle 2, 4, 8, 12) 
 
3) End of therapy 
1) 
M
andatory 
(fresh 
or 
viably 
frozen)  
 
2) 
M
andatory 
 
3) 
O
ptional 
Stanford Cancer 
Correlative 
Science 
Unit 
(CCSU) 
Bita Sahaf 
bsahaf@stanford
.edu 
5 
Sample 
Banking 
 
Sample banking for 
future study 
Mononucle
arcells and 
plasma 
from bone 
marrow in 
Sodium 
Heparin 
and EDTA 
tubes 
(Bilateral) 
Baseline if available 
 
Disease restaging (cycle 
2, 4, 8, 12) 
 
End of therapy 
Optional 
EET Biobank 
Blood-based Biomarkers 
1 
Magrolimab 
PK 
ELISA 
CLIA: N 
No 
Review 
Require
d 
Integrated 
Assess 
the 
drug 
concentrations 
achieved during this 
first in child trial 
Serum 
from 
Red 
top tube 
Safety lead-in D1, 8, 15 
Cycle 1, D1, 8, 15, ARM 
B only: D22 
Cycle 2, D1 
Cycle 3, D1 
Cycle 5, D1 
Cycle 7, D1 
Cycle 9, D1 
Cycle 11, D1 
End of therapy 
(all samples drawn prior 
to magrolimab infusion) 
M 
(safety 
cohort 
and 
first 
three 
patients 
on 
any 
expansion 
cohorts) 
PPD 
  

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 32 
 
 
Priority Biomarker 
Name 
Assay 
(CLIA: 
Y/N) 
Use 
in 
the 
Trial 
(Integral, Integrated, 
or Exploratory) AND 
Purpose 
Specimens 
Tested 
Collection Time Points Mandatory 
or Optional Assay 
Laboratory and 
Lab PI 
2 
Magrolimab 
anti-drug 
antibody 
(ADA) 
Testing  
ECLIA 
CLIA: 
N 
No 
Review 
Require
d 
Integrated 
Assess for immune 
responses against 
magrolimab  
Serum 
from Red 
top tube 
Safety lead-in D1 
Cycle 1, D1 
Cycle 2, D1 
Cycle 3, D1 
Cycle 5, D1 
Cycle 7, D1 
Cycle 9, D1 
Cycle 11, D1 
End of therapy 
(all samples drawn prior 
to magrolimab infusion) 
M (safety 
cohort and 
first three 
patients on 
any 
expansion 
cohorts) 
PPD 
3 
FcR receptor 
polymorphis
m 
RT-PCR 
CLIA: 
N 
No 
Review 
Require
d 
Exploratory 
Assess contribution of 
FcR polymorphisms to 
disease response 
PBMC 
from 
EDTA tube  
Baseline:  
 Arm A: Safety Lead In- 
Week 1, D1 
 Arm B: Cycle 1, D1 
Optional 
Sondel 
Laboratory, 
University of 
Wisconsin) 
Paul Sondel 
pmsondel@hum
onc.wisc.edu 
4 
KiR 
phenotyping 
RT-PCR 
CLIA: 
N 
No 
Review 
Require
d 
Exploratory 
Assess contribution of 
KiR mismatching to 
disease response 
PBMC 
from 
EDTA tube  
Baseline:  
 Arm A: Safety Lead In- 
Week 1, D1 
 Arm B: Cycle 1, D1 
Optional 
Sondel 
Laboratory, 
University of 
Wisconsin 
Paul Sondel 
pmsondel@hum
onc.wisc.edu  

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 33 
 
 
Priority Biomarker 
Name 
Assay 
(CLIA: 
Y/N) 
Use 
in 
the 
Trial 
(Integral, Integrated, 
or Exploratory) AND 
Purpose 
Specimens 
Tested 
Collection Time Points Mandatory 
or Optional Assay 
Laboratory and 
Lab PI 
5 
HACA 
antibody 
testing 
ELISA 
CLIA: N 
No 
Review 
Require
d 
Exploratory 
Assess contribution of 
Human anti- chimeric 
antibody response to 
disease response 
Serum 
from 
Red 
top tube  
ARM A: Cycle 1: Day 1, 
5 
ARM B: Cycle 1: Day 8, 
12 
 
Cycle 2: 
Day 1 and 5  
 
Cycle 4: 
Day 1 and 5 
End of therapy 
Mandatory 
Sondel 
Laboratory, 
University 
of 
Wisconsin 
Paul Sondel 
pmsondel@hum
onc.wisc.edu  
6 
Luminex for 
peripheral 
cytokines 
Lumine
x 
CLIA: N 
No 
Review 
Require
d 
Exploratory 
To 
assess 
for 
the 
presence 
of 
human 
cytokines 
Plasma 
from blood 
in 
EDTA 
tube  
Safety 
Lead-In 
and 
Cycles 1-2: Weekly prior 
to magrolimab infusion 
 
Subsequent cycles: Day 
1 prior to infusion  
 
End of therapy 
 
 
Mandatory 
 
Stanford Human 
Immune 
Monitoring 
Center (HIMC) 
Holden Maecker 
maecker@stanfo
rd.edu  
  
7 
CyTOF for 
peripheral 
immune 
subsets 
Mass 
Cytomet
ry 
CLIA: N 
No 
Review 
Require
d 
Exploratory 
To determine changes 
in 
the 
peripheral 
immune subsets as a 
result of treatment with 
anti-CD47/anti-GD2 
Mononucle
ar 
cells 
from blood 
in Sodium 
Heparin 
tube 
Safety 
Lead-In 
and 
Cycles 1-2: Weekly prior 
to magrolimab infusion 
 
Subsequent cycles: Day 
1  
 
End of therapy 
 
Mandatory 
  
Stanford Cancer 
Correlative 
Science 
Unit 
(CCSU) 
Bita Sahaf 
bsahaf@stanford
.edu  

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 34 
 
 
Priority Biomarker 
Name 
Assay 
(CLIA: 
Y/N) 
Use 
in 
the 
Trial 
(Integral, Integrated, 
or Exploratory) AND 
Purpose 
Specimens 
Tested 
Collection Time Points Mandatory 
or Optional Assay 
Laboratory and 
Lab PI 
8 
Sample 
Banking 
 
Sample banking for 
future studies 
 PBMCs 
from blood 
in EDTA 
Safety Lead-In and 
Cycles 1-2: Weekly 
prior to magrolimab 
infusion 
 
Subsequent cycles: Day 
1 prior to infusion  
 
End of therapy 
 
Mandatory 
(bank cells 
when 
plasma is 
collected for 
cytokines) 
EET Biobank 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
Page 35 
 
 
5.1 
Exploratory/Ancillary Correlative Studies 
 
5.1.1 
MIBI for immune cell infiltration 
 
Rationale:  Tissue will be analyzed in an attempt to understand the baseline immune cell infiltration of relapsed or refractory 
neuroblastoma and osteosarcoma. If available, clinical biopsies or surgical samples obtained during treatment or at disease 
progression will be requested. Patients enrolled in cohort 4 undergoing staged pulmonary resections will have tissue 
obtained from the initial surgical resection, and then again from the second resection after completion of one cycle of 
Hu5F9-G4 (magrolimab) and dinutuximab. 
 
Assay: Multiplexed ion beam imaging 
 
Lab(s) Performing Correlative Study: Stanford  
 
5.1.2 
Hu5F9-G4 (magrolimab) Pharmacokinetics 
 
Rationale: This blood-based biomarker will be mandatory in the patients participating in the safety cohort and in the first 
three patients enrolled in each of the expansion cohorts to assess the drug concentrations in the pediatric population.    
 
Assay: LC/MS 
 
Labs(s) Performing Correlative Study: PPD 
 
5.1.3 
Hu5F9-G4 (magrolimab) Anti-Drug Antibody (ADA) 
 
Rationale: This blood-based biomarker will be mandatory in the patients participating in the safety cohort and in the first 
three patients enrolled in each of the expansion cohorts to assess development of anti-magrolimab antibodies. 
 
Assay:  ECLIA 
 
Labs(s) Performing Correlative Study: PPD 
 
5.1.4 
FcR receptor polymorphism 
 
Rationale: The purpose of this assay is to assess the contribution of KiR mismatching to disease response in patients with 
relapsed or refractory osteosarcoma and neuroblastoma. 
 
Assay: Real-time PCR 
 
Lab(s) Performing Correlative Study: University of Wisconsin, Laboratory of Paul Sondel, MD  
5.1.5 
HACA antibody testing 
 
Rationale: The purpose of this assay is to assess the contribution of human anti-chimeric antibody response to disease 
response in patients with relapsed or refractory osteosarcoma and neuroblastoma. 
 
Assay: ELISA 
 

                              
 
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Lab(s) Performing Correlative Study: University of Wisconsin, Laboratory of Paul Sondel, MD  
 
5.1.6 
Peripheral Cytokine Assay 
 
Rationale: The purpose of this assay is to assess the presence of human cytokine response to combination therapy of Hu5F9-
G4 (magrolimab) and dinutuximab. 
 
Assay: Luminex 
 
Lab(s) Performing Correlative Study: Stanford HIMC 
 
5.1.7 
Peripheral Immune Subsets 
 
Rationale: The purpose of this assay is to assess changes in the circulating immune subsets in response to combination 
therapy of Hu5F9-G4 (magrolimab) and dinutuximab. 
 
Assay: CyTOF 
 
Lab(s) Performing Correlative Study: Stanford CCSU 
 
 
5.2 Processing and Storage of Specimens at EET Biobank 
 
• 
Processing of Tissue 
Biopsies will be processed for FFPE blocks by the sites. 
 
Biopsies will be sectioned, and H&E stained for image scanning and histopathological examination by a designated 
pathologist. The H&E section will serve to confirm concordance with the institutional diagnosis and also estimate 
percent tumor content. An adequate biopsy sample will contain at least 50% tumor cells with minimal necrosis and 
stromal tissue.  
 
Processed samples will be stored at the EET Biobank as outlined below until they are ready to be sent for analyses as 
defined in the protocol. 
 
• 
Processing of Blood and Bone marrow 
Upon receipt at the EET Biobank, fresh bone marrow in EDTA tubes and sodium heparin tubes as well as blood in 
EDTA tubes, sodium heparin tubes will be processed for mononuclear cells and plasma. Cells will be stored at 5 x 106 
cells per vial in freezing media. At C1D1, 2 mL of blood in EDTA (of the 6 mL blood in EDTA received) will be 
extracted for DNA.  
 
Frozen serum will be accessioned and stored as listed below. 
 
Viably frozen bone marrow, processed locally per institutional SOPs, for mononuclear cells and plasma, will be 
accessioned and stored as listed below.  
 
Processed samples will be stored at the EET Biobank as outlined below until they are ready to be sent for analyses as 
defined in the protocol.  
 

                              
 
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• 
Storage of Specimens at EET Biobank 
- 
Plasma and serum samples will be stored in a -80°C freezer 
- 
PBMCs will be stored in a vapor phase of liquid nitrogen (LN2) freezer 
- 
FFPE tissue blocks will be stored at ambient temperature 
- 
Snap-frozen tissue will be stored in a LN2 vapor phase freezer 
 
5.3 Summary Table for Specimen Collection 
 
Tumor Tissue Specimens at Baseline and As Available While on Study: 
Archival tumor tissue slides or block will be requested upon enrollment to the study as outlined in Table 3 below. In 
addition, clinical biopsies or surgical samples obtained during treatment or at disease progression will be requested, if 
available as outlined in Table 3 below. 
 
Table 3: Summary Table for Specimen Collection 
 
Time Point 
Specimen 
Specimen Shipment 
Archival 1 
 
• Archival Tissue: Formalin-fixed paraffin-embedded (FFPE) tumor 
tissue block (preferred) 
OR 
• 1 H&E stained slide (3-5 µm) AND, 
• 35-55 unstained, uncharged, air-dried slides (10 µm) 
EET Biobank 
 
• Archival tumor tissue: Snap frozen tumor tissue 
On Study Biopsy (Any clinical biopsies while on study)1, 3 
 
• Formalin-fixed paraffin-embedded (FFPE) tumor tissue block 
(preferred) 
OR 
• 1 H&E stained slide (3-5 µm) AND, 
• 35-55 unstained, uncharged, air-dried slides (10 µm) 
EET Biobank 
 
•  Snap frozen tumor tissue 
Cohort B4 (Tissue from metastasectomy at enrollment)1 
 
• Formalin-fixed paraffin-embedded (FFPE) tumor tissue block 
(preferred) (from multiple metastases, if present) 
OR 
• 1 H&E stained slide (3-5 µm) (from multiple metastases, if 
present) AND, 
• 35-55 unstained, uncharged, air-dried slides (10 µm) (from 
multiple metastases, if present) 
EET Biobank 
 

                              
 
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• Snap frozen tumor tissue (from multiple metastases, if present) 
Arm A: Safety Lead-In Day 1 (Week 1) (Prior to dosing) 
 
• 5mL bone marrow2, 4 in a green top (Sodium Heparin) tube 
EET Biobank 
 
• 5mL bone marrow2, 4 in a purple top (EDTA) tube 
• 2mL blood in a purple top (EDTA) tube 
• 4mL blood in a purple top (EDTA) tube 
• 5mL blood in a green top (Sodium Heparin) tube 
• 3mL blood in a red top (serum) tube 
PPD 
• 3mL blood in a red top (serum) tube 
ARM A: Safety Lead-In Day 8 (Week 2) 
 
• 3mL blood in a red top (serum) tube 
PPD 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
 
• 5mL blood in a green top (Sodium Heparin) tube 
ARM A: Safety Lead-In, Day 15 (Week 3) 
 
• 3mL blood in a red top (serum) tube 
PPD 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
 
• 5mL blood in a green top (Sodium Heparin) tube 
Arm B: Priming, Week 1, Day 1 (Prior to dosing) 
 
• 5mL bone marrow4 in a green top (Sodium Heparin) tube 
EET Biobank 
 
• 5mL bone marrow4 in a purple top (EDTA) tube 
• 2mL blood in a purple top (EDTA) tube 
• 4mL in a purple top (EDTA) tube 
• 5mL blood in a green top (Sodium Heparin) tube 
• 3mL blood in a red top (serum) tube 
PPD 
• 3mL blood in a red top (serum) tube 

                              
 
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ARM A: Cycle 1: Week 1, Day 1  
ARM B: Cycle 1: Week 2, Day 8 
 
• 3mL blood in a red top (serum) tube 
PPD 
 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
 
• 5mL blood in a green top (Sodium Heparin) tube 
Draw 
prior 
to 
dinutuximab 
infusion 
• 2mL blood in a red top tube, processed for serum and frozen5 
ARM A: Cycle 1 Week 1, Day 5  
ARM B: Cycle 1 Week 2, Day 12 
 Draw immediately 
after 
dinutuximab 
infusion 
• 2mL blood in a red top tube processed for serum and frozen5  
EET Biobank 
 
ARM A: Cycle 1 Week 2, Day 8  
ARM B: Cycle 1 Week 3, Day 15 
 
• 3mL blood in a red top (serum) tube 
PPD 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
 
• 5mL blood in a green top (Sodium Heparin) tube 
ARM A: Cycle 1 Week 3, Day 15  
ARM B: Cycle 1 Week 4, Day 22 
 
• 3mL blood in a red top (serum) tube 
PPD 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
• 5mL blood in a green top (Sodium Heparin) tube 
Cohort B4 (Tissue from metastasectomy after Cycle 1)1 
 
• Formalin-fixed paraffin-embedded (FFPE) tumor tissue block 
(preferred) (from multiple metastases, if present) 
OR 
• 1 H&E stained slide (3-5 µm) (from multiple metastases, if 
present) 
• 35-55 unstained, uncharged, air-dried slides (10 µm) (from 
multiple metastases, if present) 
EET Biobank 
• Snap frozen tumor tissue (from multiple metastases, if present) 
Cycle 2 Day 1  

                              
 
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• 3mL blood in a red top (serum) tube 
PPD 
• 3mL blood in a red top (serum) tube 
PPD 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
• 5mL blood in a green top (Sodium Heparin) tube 
Draw 
prior 
to 
dinutuximab 
infusion 
• 2mL blood in a red top tube, processed for serum and frozen5  
Cycle 2 Day 5  
Draw 
after 
dinutuximab 
infusion 
• 2mL blood in a red top (serum) tube5  
EET Biobank 
Cycle 2 Day 8  
 
 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
• 5mL blood in a green top (Sodium Heparin) tube 
Cycle 2 Day 15  
 
 
• 4mL blood in a purple top (EDTA) tube 
EET Biobank 
• 5mLblood in a green top (Sodium Heparin) tube 
End of Cycle 2 and all restaging (Cycle 4, 8, and 12) 
 
 
• 5mL bone marrow2 in a green top (sodium heparin) tube 
EET Biobank 
• 5mL bone marrow2 in a purple top (EDTA) tube 
Cycle 3, 5, 7, 9, 11 Day 1  
 
 
• 3mL blood in a red top (serum) tube 
PPD 
• 3mL blood in a red top (serum) tube 
PPD 
Cycle 3-12 Day 1 
 
 
• 4 mL blood in a purple top (EDTA) tube  
EET Biobank 
• 5mL blood in a green top (Sodium Heparin) tube 
Cycle 4 Day 1  
Draw 
prior 
to 
dinutuximab 
infusion 
• 2mL blood in a red top tube, processed for serum and frozen5  
EET Biobank 
Cycle 4 Day 5  

                              
 
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Draw 
after 
dinutuximab 
infusion 
• 2mL blood in a red top (serum) tube5 
EET Biobank 
End of Therapy or Progression 
 
• 3mL blood in a red top (serum) tube 
PPD 
• 3mL blood in a red top (serum) tube 
PPD 
• 2mL blood in a red top tube, processed for serum and frozen 
EET Biobank 
• Formalin-fixed paraffin-embedded (FFPE) tumor tissue block 
(preferred)1, 3 
OR 
• 1 H&E stained slide (3-5 µm) 
• 35-55 unstained, uncharged, air-dried slides (10 µm) 
• Snap frozen tumor tissue1, 3 
• 5mL bone marrow2 in a green top (sodium heparin) tube 
• 5mL bone marrow2 in a purple top (EDTA) tube 
• 4mL blood in a purple top (EDTA) tube  
• 5mL blood in a green top (Sodium Heparin) tube 
1 For all tissue a copy of the corresponding anatomic pathology report must be sent with the tissue and uploaded to Rave.  
If submitting slides, then slides must be processed in order, and numbered sequentially (e.g., H&E stained slide is created first 
and labeled 1, unstained slides are then created and numbered 2 – 56). 
2 For bone marrow aspirate or biopsy, the corresponding bone marrow report must be submitted uploaded to Rave and sent with 
the specimen to the EET Biobank. 
3 Two (2) core biopsies will be used for FFPE and three (3) additional cores will be snap-frozen. Each core biopsy must be 
embedded in a separate block. See details in section 5.6.2. 
4 Fresh or viably frozen bone marrow aspirate can be accepted prior to the Priming dose (Week 1, Day 1). Fresh bone marrow 
aspirate must be collected and shipped to the EET Biobank following patient enrollment in OPEN, and prior to the Priming 
dose (Week 1, Day 1). If available, frozen bone marrow aspirate collected within 4 weeks (28 days) of the Priming dose (Week 
1, Day 1) can be provided to the EET Biobank instead of fresh bone marrow. 
5 Specimen can be stored in the refrigerator if Dinutuximab infusion ends at a time where specimen processing is not possible 
(Friday night or over the weekend). Processing should be done no more than 3 days following collection.  
 
5.4 
Specimen Procurement Kits and Scheduling 
 
5.4.1 
Specimen Procurement Kits  
 
Kits for the collection and shipment of specimens frozen tissue to the EET Biobank can be ordered online via the Kit 
Management system (https://kits.bpc-apps.nchri.org).   
 

                              
 
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Users at the clinical sites will need to set up an account in the Kit Management system and select PED-CITN-03 protocol 
to request a kit. Please note that PED-CITN-03 may include more than one type of kit. Each user may order two kit types 
per kit type per day (daily max = 6 kits). Kits are shipped ground, so please allow 5-7 days for receipt. A complete list of 
kit contents for each kit type is located on the Kit Management system website and in the instructions included with the 
kits. 
 
Note: Kits or supplies are only provided for specimens shipped to the EET Biobank. Institutional supplies must be used for 
all other specimen collection and processing. 
 
5.4.1.1 
Scheduling of Specimen Collections 
 
Please adhere to the following guidelines when scheduling procedures to collect tissue:  
 
• 
Tumor tissue specimens collected during biopsy procedures for clinical indications will be fixed in formalin and 
embedded prior to shipment. These tissues can be collected on any day.  
• 
Specimens submitted frozen can be collected on any day but must be stored frozen and shipped to the EET Biobank 
on Monday through Thursday. In the event that frozen specimens cannot be shipped immediately, they must be 
maintained in a -70°C to -80°C freezer. 
• 
Fresh blood or bone marrow specimens may be collected and shipped Monday through Friday.  
 
5.5 
Specimen Labeling 
 
Blood and Bone Marrow Aspirate Specimen Labels  
 
Include the following on blood and bone marrow aspirate specimens (including whole blood or bone marrow and frozen, 
processed blood or bone marrow products – like serum, plasma, and mononuclear cells):  
- 
 Study ID 
- 
COG Patient ID Number (a unique patient identification number assigned via the COG Registry in the OPEN system 
at registration) 
- 
Timepoint  
- 
Specimen type (e.g., Blood, serum, bone marrow, plasma, mononuclear cells) 
- 
Laterality (R for right or L for left), if bone marrow (to be added by hand) 
- 
Collection date and time (to be added by hand) 
 
Tissue Specimen Labels  
 
Include the following on all tissue specimens or containers (e.g., cryovial or block): 
- 
Study ID 
- 
COG Patient ID Number 
- 
Timepoint  
- 
Specimen type (e.g., formalin-fixed paraffin-embedded [FFPE] Block, Formalin Fixed Tissue, Fresh Tissue in 
Media, etc.) 
- 
Tissue type (P for primary, M for metastatic or N for normal) 
- 
Surgical pathology ID (SPID) number (when applicable)  
- 
Block number from the corresponding pathology report (if available) 
- 
Collection date (to be added by hand) 
- 
Slide section number (only if tissue is submitted as slides) (to be added by hand) 
 

                              
 
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5.6 
Specimen Collection 
 
5.6.1 
Archival or Formalin-Fixed Paraffin-Embedded (FFPE) Tumor Specimen 
 
If previously-collected FFPE tissue will be submitted, then the following criteria must be met: 
 
• 
Tissue must have been collected within 6 months prior to registration  
• 
FFPE tumor tissue block(s) must be submitted.  The optimal block is at least 50% tumor.  Specimen size requirement 
is as follows: 
o Surface area:  25 mm2 is optimal.  Minimum is 5 mm2. 
o Volume:  1 mm3 optimal.  Minimum volume is 0.2 mm3, however the success of DNA extraction decreases 
at suboptimal tissue volume. 
 
If an existing block cannot be submitted, the following are requested, if available: 
• 
One (1) H&E slide (3-5 µm) 
• 
Thirty-five to fifty-five (35 – 55) 10 µm unstained air-dried uncharged slides  
 
Process and number slides sequentially (e.g., H&E stained slide should be created first and labeled with “1,” and additional 
unstained slides should be processed next and be labeled 2 – n). 
 
See Section 5.5  for labeling instructions. 
 
5.6.2 
FFPE and Frozen Tumor Biopsies 
 
• 
Biopsy Specimen Collection Procedure (does not apply to metastasectomy) 
 
-  Core biopsies at least 1 cm in length will be obtained through Interventional Radiology by a percutaneous approach 
using a 16-18-gauge needle. Only percutaneous biopsies will be performed on patients with solid tumors. However, 
excisional biopsy or endoscopic biopsy is allowed if medically indicated and can be used for analysis.  
-  Two (2) core biopsies will be used for FFPE and three (3) additional cores will be snap-frozen. If tissue is limited, 
equally divide samples between FFPE and snap-frozen. 
- 
If fine needle aspiration (FNA) is available, especially for sampling of bone lesions in order to assure specimen 
adequacy and to avoid specimen decalcification, use of FNA before core needle biopsy is preferred. Real-time 
cytopathologic immediate evaluation of the FNA specimen can confirm that the chosen target area of a lesion is 
satisfactory for obtaining the core needle biopsy specimens. If real-time cytopathology assessment of FNA 
specimens is not available, collection of FNA specimens prior to core needle biopsy procurement is recommended. 
FNA specimens are not an acceptable substitute for tissue biopsy cores; do not submit to the EET Biobank. 
- 
For pathologic examination of removed tissue, place a portion of the biopsy specimen in a labeled specimen 
container with fixative for transport to your Pathology Department. (This specimen container is not provided in the 
shipping kit.) The pathology report must be uploaded to Medidata Rave as soon as available. 
- 
These instructions also apply to additional specimens from medically necessary surgical procedures performed for 
clinical care. 
 
• 
Formalin Fixation of Tissue 
 

                              
 
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- 
Tissue must be fixed in formalin for 12-24 hours and each core biopsy must be embedded in a separate block. 
Embedding must be completed within 72 hours of adding 70% ethanol to tissue. Sites must use automated tissue 
processors and not use microwave tissue processors. Sites should follow embedding protocols where the total 
processing time from 70% ethanol to block embedding exceeds 4 hours. Tissue fixed in formalin for 24-36 hours 
prior to embedding should be shipped but will be recorded as non-compliant.  
- 
Neutral-buffered formalin must be used as fixative (no acid-based products).   
- 
The optimal block is at least 70% tumor. Specimen size requirements are as follows: 
- 
Surface area: 25 mm2 optimal (minimum 5 mm2) 
- 
Volume: 1 mm3 optimal (minimum 0.2 mm3) 
 
5.6.3 
Blood and Bone Marrow Sample Collection Procedures 
 
• 
Collection in EDTA Purple-Top Tubes 
1. Label EDTA tube(s) according to instructions in Section 5.5.2. 
2. Collect blood in EDTA Purple-Top tube(s) and gently invert 5-10 times to mix. 
3. Maintain specimens at ambient temperature (room temperature) during collection and transport.  
4. Ship on day of collection (whenever possible) to the EET Biobank according to instructions in Section 5.7. 
 
• 
Collection in Sodium Heparin Green-Top Tubes 
1. Label sodium heparin tube(s) according to instructions in Section 5.5.2.  
2. Collect blood in sodium heparin tubes and gently invert 5-10 times to mix. 
3. Maintain specimens at ambient temperature (room temperature) during collection and transport.  
4. Ship on day of collection (whenever possible) to the EET Biobank according to instructions in Section 5.7. 
 
• 
Collection in Red Top Serum Tubes for the EET Biobank 
1. Label Red Top Serum (RTS) tube according to instructions in Section 5.5.2.  
2. Collect 2 mL of whole blood using a Red Top Serum (RTS) tube. Invert the collection tube 8 – 10 times (gently) to 
facilitate the clotting process.   
3. Allow blood to clot upright at room temperature for at least 30 minutes (maximum 60 minutes) prior to processing.  
If the blood is not immediately processed after the clotting period, then tubes should be stored (after the 30-60 
minutes of clotting time) at 4°C for no longer than 4 hours. Process serum from red top tubes by centrifuging for 
10 minutes at 1,200 × g at room temperature. 
4. Using a clean transfer pipette, aliquot serum into the labeled (using the label printed from the ETCTN Specimen 
Tracking System or following the instructions in Section 5.4.2) cryovials at an aliquot volume of 1 mL per tube. 
Avoid picking up red blood cells when aliquoting by keeping the pipet above the red blood cell layer and leaving a 
small amount of serum in the tube. Tightly secure the cap of the vials before storage. Aliquoting and freezing of 
serum specimens should be completed within 1 hour of centrifugation. 
5. Store serum cryovials upright in a specimen box or rack in an -70°C to -90°C or colder freezer prior to shipping to 
the EET Biobank. Do not allow specimens to thaw after freezing. 
6. Ship on day of collection (whenever possible) to the EET Biobank according to instructions in Section 5.7. 
 
• 
Collection in Red Top Serum Tubes for Hu5F9-G4 PK testing (PPD) 
1. Label Red Top Serum (RTS) tube according to instructions in Section 5.5.2.  
2. Collect 3 mL of whole blood using a Red Top Serum (RTS) tube. Invert the collection tube 8 – 10 times (gently) to 
facilitate the clotting process.   
 
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of 1 hour from the time of collection. 
 
3. Centrifuge Red Top Serum (RTS) tubes(s) for 10 minutes at 1,000-1,300 RCF (g) in a swing bucket centrifuge (15 
minutes using a fixed-angle centrifuge). 
4. Using a plastic transfer pipette, transfer equal aliquots (~ 0.4 mL) of the serum layer to the corresponding cryovials.  
In the event you do not yield enough serum for 4 equal aliquots (~0.4 mL), fill the first 3 aliquots with 0.4 mL 
of serum first.  Then fill the remaining cryovials equally with the remaining serum.  
5. Allow enough space between the serum and tube caps to account for expansion during freezing. Do not overfill.  
Cap the cryovial and place immediately upright on ice.  
6. Freeze immediately at -70° C until shipment.   
7. Ship frozen to PPD weekly if possible. Otherwise, ship to PPD day of collection. 
 
• 
Collection in Red Top Serum (RTS) tubes for Magrolimab anti-drug antibody (ADA) testing (PPD) 
1. Label Red Top Serum (RTS) tube according to instructions in Section 5.5.2.  
2. Collect 3 mL of whole blood using a Red Top Serum (RTS) tube. Invert the collection tube 8 – 10 times (gently) to 
facilitate the clotting process.   
 
Note: Serum should be physically separated from contact with the cells soon as possible with a maximum time limit 
of 1 hour from the time of collection. 
 
3. Centrifuge Red Top Serum (RTS) tubes(s) for 10 minutes at 1,000-1,300 RCF (g) in a swing bucket centrifuge (15 
minutes using a fixed-angle centrifuge). 
4. Using a plastic transfer pipette, transfer equal aliquots (~ 0.4 mL) of the serum layer to the corresponding cryovials.  
In the event you do not yield enough serum for 4 equal aliquots (~0.4 mL), fill the first 3 aliquots with 0.4 mL 
of serum first.  Then fill the remaining cryovials equally with the remaining serum.  
5. Allow enough space between the serum and tube caps to account for expansion during freezing. Do not overfill.  
Cap the cryovial and place immediately upright on ice.  
6. Freeze immediately at -70° C until shipment.   
7. Ship frozen to PPD weekly if possible. Otherwise, ship to PPD day of collection. 
 
5.7 
Shipping Specimens from Clinical Sites to the EET Biobank 
 
5.7.1 
General Shipping Information 
 
When kits are provided, the shipping container sent with kit contents should be used to ship specimens.  
 
For all tissue, the corresponding pathology report is required.  
 
• 
Tissue embedded in paraffin may be batched and shipped Monday through Thursday. 
 
• 
Frozen specimens (tissue, serum, bone marrow) may be shipped Monday through Thursday.  
 
• 
Fresh blood and Bone marrow must be shipped overnight on the same day as collection for arrival on Tuesday through 
Saturday at the EET Biobank. Saturday delivery is only available for shipments of fresh blood or bone marrow.  
 
• 
The date and time of collection and shipping date must be entered into the ETCTN STS for all submitted specimens.  
 

                              
 
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• 
Do not ship specimens the day before a U.S. federal holiday. If you are unsure whether the EET Biobank will be able 
to receive specimens, then please contact the EET Biobank. 
 
5.7.2 
Additional Shipping Information 
 
Shipping of FFPE Blocks and Glass Slides Using Supplies Provided by the Institution 
 
1. Before packaging blocks or slides, verify that each specimen is labeled according to Section 5.4.2. 
2. Blocks should be placed in a hard-sided container, preferably a special block holder, to protect the specimen. Glass 
slides are to be placed in plastic slide holders.  Place tissue paper on top of the separated slides prior to closing the 
slide holder to reduce slide movement during shipment. 
3. Place the blocks or slides in a reinforced cardboard shipping box with appropriate packaging filler to minimize 
movement of specimens within the shipping box. 
4. Include a copy of the forms listed above and a shipping manifest from the Specimen Tracking System with each 
shipment.  
5. Please include a cold pack when shipping on hot days and extra insulation on cold days. 
6. Ship specimens to the address listed below. FedEx Priority Overnight is strongly recommended to prevent delays 
in package receipt.  
 
Shipping Blood or Bone Marrow Using Supplies Provided by the Institution 
 
1. Before packaging specimens, verify that each specimen is labeled according to the instructions in 5.4.2. 
2. Place the collection tubes into zip-lock bags.   
3. Next, place specimens into a biohazard envelope with absorbent material. Expel as much air as possible and seal 
the envelope securely.  
4. Place the biohazard envelope into a Tyvek envelope. Expel as much air as possible and seal securely. 
5. Place packaged collection tube(s) and a copy of the shipping manifest from the Sample Tracking System into a 
sturdy shipping container.  In winter months, please use an insulated container and include extra insulation (such as 
bubble wrap) inside the shipping container to prevent specimens from freezing. 
6. Close the container and tape shut. 
7. Attach a shipping label to the top of the shipping container.  
8. Attach an Exempt Human Specimen sticker to the side of the container. 
9. Ship specimens via overnight courier to the address below. FedEx Priority Overnight is strongly recommended to 
prevent delays in package receipt.  
 
Shipping Frozen Serum Using Supplies Provided by the Institution 
 
1. Before packaging specimens, verify that each specimen is labeled according to the instructions in 5.4.2 and the lids 
of all primary receptables containing liquid are tightly sealed.   
2. Place the specimens in zip-lock bags.  Use a separate zip-lock bag for each specimen type and time point.  
3. Place the zip-lock bags in a biohazard envelope containing absorbent material.  Expel as much air as possible and 
seal securely.  
4. Put the secondary envelope into a Tyvek envelope. Expel as much air as possible and seal securely.  
5. Place frozen specimens in the insulated shipping container with dry ice.  Layer the bottom of the compartment with 
dry ice until it is approximately one-third full.  Place the frozen specimens on top of the dry ice.  Cover the specimens 
with the dry ice until the shipping container is almost completely full.  When packaging specimens, ensure that you 
leave enough room to include at least 5 pounds of dry ice in the shipment.  
6. Insert a copy of the required forms into a plastic bag and place in the shipping container. 
7. Close the lid of the shipping container and tape it shut with durable sealing tape.  Do not completely seal the 

                              
 
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container. 
8. Complete a FedEx air bill and attach to top of shipping container. 
9. Complete a dry ice label. 
10. Attach the dry ice label and an Exempt Human Specimen sticker to the side of the shipping container. 
11. Ship specimens via overnight courier to the address below.  FedEx Priority Overnight is strongly recommended to 
prevent delays in package receipt.  
 
Shipping Frozen Tissue in a Single-Chamber Kit 
 
1. Before packaging specimens, verify that each specimen is labeled according to the instructions in 5.4.2.  
2. Place the specimens in zip-lock bags.  Use a separate zip-lock bag for each specimen type and time point.  
3. Place the zip-lock bags in the biohazard envelope containing absorbent material.  Expel as much air as possible and 
seal securely.  
4. Put the secondary envelope into a Tyvek envelope.  Expel as much air as possible and seal securely.  
5. Place frozen specimens in the kit compartment with dry ice.  Layer the bottom of the compartment with dry ice 
until it is approximately one-third full.  Place the frozen specimens on top of the dry ice.  Cover the specimens with 
the dry ice until the compartment is almost completely full.  When packaging specimens, ensure that you leave 
enough room to include at least 5 pounds of dry ice in the shipment.  
6. Insert a copy of the required forms into a plastic bag and place in the kit chamber. 
7. Place the Styrofoam lid on top to secure specimens during shipment.  Do not tape the inner chamber shut. 
8. Close the outer lid of the Specimen Procurement Kit and tape it shut with durable sealing tape.  Do not completely 
seal the container. 
9. Complete a FedEx air bill and attach to top of shipping container. 
10. Complete a dry ice label. 
11. Attach the dry ice label and an Exempt Human Specimen sticker to the side of the shipping container. 
12. Ship specimens via overnight courier to the address below. FedEx Priority Overnight is strongly recommended to 
prevent delays in package receipt.  
 
5.7.3 
Required Forms for Specimen Submissions 
 
Sample label data should be entered into the specimen transmittal forms in RAVE for tumor tissue and bone marrow 
samples. Sample label data for blood should be recorded on the sample worksheets, which must accompany the sample 
shipments and be uploaded to RAVE. See below for required forms.  
 
 
Required Forms 
Tissue 
1.Specimen transmittal forms in RAVE 
2.Corresponding Pathology Report 
Bone Marrow Aspirate  
1.Specimen transmittal forms in RAVE 
2.Corresponding Bone Marrow Report (once available) 
Blood or Serum 
See the following appendices: 
Appendix G: Pharmacokinetic Worksheet for Magrolimab, Arm 
A 
Appendix H: Pharmacokinetic Worksheet for Magrolimab, Arm 
B 
Appendix I: Anti-Drug Antibody (ADA) Worksheet for 

                              
 
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Magrolimab 
Appendix J: FcR Receptor for Polymorphism Worksheet for Arm 
A 
Appendix K: FcR Receptor for Polymorphism Worksheet for 
Arm B 
Appendix L: KiR Phenotyping Worksheet for Arm A 
Appendix M : KiR Phenotyping Worksheet for Arm B 
Appendix N: Human Anti-Chimera Antibodies (HACA) Testing 
Worksheet Arm A 
Appendix O: Human Anti-Chimera Antibodies (HACA) Testing 
Worksheet Arm B  
Appendix P: Luminex for Peripheral Cytokines Worksheet for 
Arm A 
Appendix Q: Luminex for Peripheral Cytokines Worksheet for 
Arm B 
Appendix R: CyTOF for Peripheral Immune Subsets Worksheet 
for Arm A 
Appendix S: CyTOF for Peripheral Immune Subsets Worksheet 
for Arm B 
Appendix T: Sample Banking Worksheet for Arm A 
Appendix U: Sample Banking Worksheet for Arm B 
Appendix V: Central Monitoring Plan 
 
5.7.4 
Shipping address 
 
Ship specimens to the address below using overnight courier, early morning delivery option: 
 
EET Biobank Nationwide Children’s Hospital 
700 Children’s Dr., WA1340 
Columbus, OH 43205 
Phone: (614) 722-2865 
Fax: (614) 722-2897 
Email: BPCBank@nationwidechildrens.org 
 
FedEx Priority Overnight service is very strongly preferred.  
 
Please see the FedEx Account Usage Guidelines Memo here 
 
• 
Contact Information for Assistance 
 
For all queries, please use the contact information below: 
 
EET Biobank  
Toll-free Phone: (800) 347-2486 
Email: BPCBank@nationwidechildrens.org  
 
 
5.8 
Shipping Specimens from Clinical Sites to Specific Laboratories 
 

                              
 
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5.8.1 
Shipping Hu5F9-G4 PK Test Specimens to PPD 
 
Standard procedures for packing specimens should be used (e.g., cryopreserved blood samples). Priority Overnight shipping 
is required for all specimens. 
 
Ship samples to the following: 
 
ATTN: LiMajor Pittman  
PPD  
2246 Dabney Road  
Richmond, VA 23230  
Phone: 804.977.8459  
 
5.8.2 
Shipping Hu5F9-G4 (Magrolimab) ADA to PPD 
 
Standard procedures for packing specimens should be used (e.g., cryopreserved blood samples). Priority Overnight shipping 
is required for all specimens. 
 
Ship samples to the following: 
 
ATTN: LiMajor Pittman  
PPD  
2246 Dabney Road  
Richmond, VA 23230  
Phone: 804.977.8459  
 
6 
TREATMENT AND IMAGING PLAN 
 
This is a phase 1 trial dose finding trial with Hu5F9-G4 (magrolimab) a recombinant humanized IgG4 monoclonal antibody, 
given in combination with dinutuximab (Unituxin®), a GD2-binding monoclonal antibody for children and young adults 
with relapsed/refractory (R/R) NB and relapsed osteosarcoma. The first cohort of patients will receive a Safety Lead-In of 
single agent Hu5F9-G4 (magrolimab) at Dose Level 1 (30 mg/kg) followed by Hu5F9-G4 (magrolimab) in combination 
with dinutuximab as described in Section 6.1.1. Once the safe dose of the combination is established, patients will be 
enrolled to one of four expansion cohorts who receive the combination of Hu5F9-G4 (magrolimab) at the recommended 
phase 2 dose (RP2D) and a fixed dose of dinutuximab as outlined in Section 6.4. 
 
Treatment will be administered on both an inpatient and outpatient basis. Dinutuximab is administered inpatient, while 
Hu5F9-G4 (magrolimab) can be given on an outpatient basis.  
 
Reported adverse events and potential risks are described in Section 10. Appropriate dose modifications are described in 
Section 7.  
 
No investigational or commercial agents or therapies other than those described below may be administered with the intent 
to treat the patient's malignancy.  
 
The Study Calendars in Section 11 outline the timing of procedures and visits. 
 
6.1 
Agent Dose and Administration 
 

                              
 
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All patients, regardless of whether they are enrolled on the “single agent Safety Lead-In” Dose Finding Cohort (Arm A) or 
the Expansion Cohorts (Arm B), will receive a priming dose of Hu5F9-G4 (magrolimab) (1 mg/kg) intravenous (IV) on 
Day 1 of week 1 (see Figure 1 and Figure 2).  
 
6.1.1 
Dose Finding Cohort (Arm A) 
 
There will be two evaluations for dose limiting toxicity (DLT) conducted on this study in Arm A (see Figure 1 and Figure 
2).  
 
6.1.1.1 
Safety Assessment During “single agent Safety Lead-In”  
 
Patients aged ≥2 or < 18 years of age will be enrolled on the “single agent Safety Lead-In”, and will receive a therapeutic 
dose of Hu5F9-G4 (magrolimab) (30 mg/kg IV) on Day 1 of weeks 2 and 3 for a 21-day “single agent Safety Lead-In” cycle 
(see Figure 1 and Figure 2). An assessment for DLTs as defined in Section 6.3 will be performed during and at the end of 
the 21-day “single agent Safety Lead-In”.  
 
Any patient who does not develop DLT during the “single agent Safety Lead-In” may proceed to Cycle 1 (combination 
therapy with Hu5F9-G4 (magrolimab) plus dinutuximab) and will be evaluable for safety assessment during and after Cycle 
1. When dinutuximab is administered immediately after Hu5F9-G4 (magrolimab), redosing with acetaminophen and 
diphenhydramine is not necessary. The intravenous line should be flushed well between drug administrations. 
 
Patient enrollment and start of treatment during the safety “single agent Safety Lead-In” assessment will be staggered by 7 
days for each patient enrolled. Three patients will initially be enrolled at Dose Level 1 (30 mg/kg IV).  
 
• 
If 0 of the initial 3 patients develops a DLT during the 21-day “single agent Safety Lead-In”, the next phase of safety 
will be evaluated in Cycle 1 as outlined below (Section 6.1.1.2).  
 
• 
If 1 of the initial 3 patients develops a DLT (Section 6.3) during the 21-day “single agent Safety Lead-In”, then an 
additional 3 patients will be enrolled at Dose Level 1. 
 
o If 0 of these 3 additional patients (totaling 1/6) develops a DLT during the 21-day “single agent Safety Lead-
In”, the study will continue to evaluate DLTs in Cycle 1 as outlined below (Section 6.1.1.2).   
o If ≥1 of these 3 additional patients (totaling 2/6) develop a DLT, the dose of Hu5F9-G4 (magrolimab) will be 
de-escalated to Dose Level -1 (20 mg/kg) during weeks 2 and 3 in the next 3 patients. The safety of Dose Level 
-1 will be similarly evaluated in 3-6 patients. 
 
• 
If ≥ 2 of the initial 3 patients develop a DLT during the 21-day “single agent Safety Lead-In”, the dose of Hu5F9-G4 
(magrolimab) will be de-escalated to Dose Level -1 (20 mg/kg) during weeks 2 and 3, in the next 3 patients. The safety 
of Dose Level -1 will be similarly evaluated in 3-6 patients.  
 
• 
If ≥ 2 patients develop DLT during the “single agent Safety Lead-In” using Dose Level -1, enrollment will pause 
pending discussions with the sponsor, IRB and FDA. 
 
Any patient who develops a DLT during the “single agent Safety Lead-In” will be removed from additional therapy on this 
study.  
 
6.1.1.2 
Safety Assessment During Cycle 1 
 
An assessment for DLTs will be performed during and at the end of the 21 days of Cycle 1 (Figure 2). In the absence of 

                              
 
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DLTs or progressive disease (PD), patients may proceed to a maximum of 12 cycles of combination therapy. After Cycle 
2, each subsequent cycle will consist of Hu5F9-G4 (magrolimab) administered on Day 1 of weeks 1 and 3 of the cycle 
(week 2 will be a week of rest), with dinutuximab administration on Day 2 through 5 of week 1.   
 
The initial dosing of each patient during Cycle 1 safety assessment will be staggered by 7 days for each patient. Three weeks 
(21 days) must elapse after completion of Cycle 1 in the final patient in the dose finding cohort (Arm A) to allow for safety 
assessment before treating additional patients at the determined recommended phase 2 dose (RP2D) in Arm B. 
 
The following rules apply to the DLT assessment conducted at the conclusion of Cycle 1 (week 6). 
 
If Dose Level 1 is selected as safe for Cycle 1 based on safety results from the ‘Single agent Safety Lead-In’, three patients 
will be enrolled, and the following applies: 
 
• 
If 0 of the initial 3 patients develops a DLT during Cycle 1, the study will proceed to the expansion cohorts (Arm B) 
(see Section 6.4). 
 
• 
If 1 of the initial 3 patients develops a DLT during Cycle 1, then an additional 3 patients will be enrolled at Dose Level 
1.   
 
o If 0 of these 3 additional patients (totaling 1/6) develops a DLT during Cycle 1, the study will proceed to the 
expansion cohorts (Arm B) (see Section 6.4).  
 
• 
If ≥ 1 of these 3 additional patients (totaling ≥ 2/6) develop a DLT during Cycle 1, an additional 3 patients will be 
enrolled to receive the priming dose followed by Hu5F9-G4 (magrolimab) de-escalated to Dose Level -1 (20 mg/kg) 
during Cycle 1 (Table 4). The safety of Dose Level -1 will be similarly evaluated in 3-6 patients.  
 
• 
If 2 of the initial 3 patients develop a DLT during Cycle 1, an additional 3 patients will be enrolled to receive the 
priming dose followed by Hu5F9-G4 (magrolimab) de-escalated to Dose Level -1 (20 mg/kg) during Cycle 1. The 
safety of Dose Level -1 will be similarly evaluated in 3-6 patients. 
 
Table 4: Doses for Hu5F9-G4 (magrolimab) and Dinutuximab during Dose Finding Cohort (Cycle 1) 
 
Dose Level 
Dose 
of 
Hu5F9-G4 
(magrolimab) 
Dose of Dinutuximab 
Level -1 
20 mg/kg IV  
17.5 mg/m2 IV 
Level 1 
30 mg/kg IV  
17.5 mg/m2 IV 
 
The dose level of Hu5F9-G4 (magrolimab) that is deemed safe during both the ‘Single agent Safety Lead-In’ and Cycle 1 
in the dose finding cohort (Arm A) will be used to evaluate safety in the Arm B schedule. The first three (3) patients enrolled 
to Arm B will be evaluated for DLT, and three weeks (21 days) must elapse after completion of Cycle 1 in the final patient 
to allow for safety assessment before treating additional patients in Arm B to confirm the recommended phase 2 dose 
(RP2D) (Arm B) (see Section 6.2.1.2). These three patients will be allocated and analyzed in their respective cohorts for 
efficacy analysis. 
If protocol therapy is delayed (due to re-scheduling for administrative reasons or temporary suspension due to toxicity), 
disease evaluations and correlative exploratory biology studies will follow the originally scheduled calendar dates and 
should not be adjusted for the dose delay. The results of these evaluations and assays while on treatment should reflect the 
effect of the former dose(s), not the current/prospective clinical status at the time of drug administration. All clinical 
assessments and laboratory tests (and their respective windows) will adjust with the dose delay to reflect the patient’s clinical 

                              
 
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status at the time of drug administration.  
 
The Study Calendars in Section 11 outline the timing of procedures and visits for Arm A and Arm B. 
 
6.2 
Regimen Description and Supportive Care Guidelines 
 
6.2.1 
Hu5F9-G4 (Magrolimab) and Dinutuximab (Unituxin®) Agent Administration 
 
6.2.1.1 
Dose Finding Cohort (Arm A) Regimen 
 
Table 5: Regimen Description for Dose Finding Cohort (Arm A) 
 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length 
Hu5F9-G4 
(magrolimab) 
Administer according 
to 
guidelines 
in 
Section 
6.2.1.3. 
Acetaminophen oral 
(PO) 
and 
diphenhydramine 
(IV) or a comparable 
regimen up to 15 
minutes before the 
first two doses of 
Hu5F9-G4 
(magrolimab), and in 
case of re-priming of 
the patient after > 4 
weeks interruption in 
treatment.  
Monitor for infusion 
reactions during and 
for 
1-hour 
post 
infusion during the 
priming dose. Any 
patients 
experience 
AEs 
during 
this 
period 
should 
be 
monitored 
as 
clinically 
indicates 
for up to 24 hours 
post 
infusion. 
Treatment of infusion 
reactions will be as 
clinically indicated. 
10 mg/kg (max 650 
mg) 
of 
acetaminophen; 0.5 
- 1 mg/ kg (max 50 
mg) 
of 
diphenhydramine^ 
Acetaminophen 
PO; 
Diphenhydramin
e IV 
Priming:  
Day 1, Week 1 
21 days  
(3 
weeks) 
 
 
 
Priming: 
Hu5F9-
G4 (magrolimab) - 
1 mg/kg 
Priming: 
Infuse 
IV (peripheral or 
central line) over 
3 hours (± 30 
min) 
“Single 
Agent 
Safety 
Lead-In”:  
Hu5F9-G4 
(magrolimab) 
30 
mg/kg* 
Subsequent 
infusions: Infuse 
IV over 2 hours 
(± 10 min) 
“Single Agent 
Safety 
Lead-
In”: 
Day 
1, 
Weeks 2 and 3 
Cycles 
1 
and 
subsequent cycles: 
Hu5F9-G4 
(magrolimab) 
30 
mg/kg* 
Cycle 1:  
Day 1, Weeks 
1, 2 and 3 
Cycle 2: Day 1 
Weeks 1, 2 and 
3 
Cycle 3 and 
subsequent 
cycles: Day 1 
of Weeks 1 and 
3 of each cycle 
(Week 
2 
is 
skipped)** 
Dinutuximab Administration 
requires 
premedication 
10 mg/kg (max 650 
mg) 
of 
acetaminophen; 0.5 
Acetaminophen 
PO 
Diphenhydramin
Cycles 1 (Week 
1): Days 2-5;  
 

                              
 
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(acetaminophen 
- 
oral, 
diphenhydramine 
- 
IV, and analgesia) 
and hydration prior to 
initiation according to 
Section 6.2.1.4 
 
 
 
 
 
 
Administer 
0.9% 
Sodium 
Chloride 
Injection 
USP 
10 
mL/kg as an IV over 1 
hour prior to initiating 
drug infusion 
- 1 mg/ kg (max 50 
mg) 
of 
diphenhydramine^ 
Analgesia 
per 
section 6.2.1.4 
 
Dinutuximab - 17.5 
mg/m2 
e^ IV (no need to 
be 
repeated 
if 
dinutuximab 
immediate 
follows previous 
drug infusion) 
 
Analgesia 
as 
described below 
in 
Section 
6.2.1.4. 
Dinutuximab 
in 
100 mL bag of 
0.9% 
Sodium 
Chloride 
Injection 
USP 
(mix by gentle 
inversion - DO 
NOT shake) 
Cycle 2 (Week 
1): Days 2-5;  
 
Subsequent 
cycles: Days 2-
5 of the first 
week of each 
subsequent 
cycle 
*  Dose will be de-escalated to 20 mg/kg if 2 or more patients develop DLT during the ”Single Agent Safety Lead-In” 
or Cycle 1. 
** Cycles may be repeated as long as the patient does not have unacceptable toxicity (see Section 6.3 or Section Error! 
Reference source not found.) or disease progression to a maximum of 12 cycles  
^ Hydroxyzine (0.5-1 mg/kg, Max dose 50 mg) PO may substitute for diphenhydramine 
 
6.2.1.2 
Expansion Cohorts (Arm B) Regimen 
 
Once the RP2D is determined from the dose finding cohort, 4 expansion cohorts will be enrolled on Arm B on this study as 
defined in Section 6.4. Expansion cohorts B1-B3 will receive a priming dose of Hu5F9-G4 (magrolimab) (1 mg/kg) on 
week 1, followed in week 2 with Hu5F9-G4 (magrolimab) administered at RP2D on Day 1 and dinutuximab 17.5 mg/m2 on 
Days 2-5. Hu5F9-G4 (magrolimab) will be administered at RP2D on Day 1 of week 3 and 4. A maximum of 12 cycles (see 
Table 6) can be completed in the absence of DLT or disease progression.   
 
Patients in Arm B Cohort B4 will be enrolled in two subgroups: 
 
1. Those who are scheduled for resection of lung lesion(s) (preferred), or those who have recently undergone resection 
of lung lesion(s) will start the Hu5F9-G4 (magrolimab)/dinutuximab within four weeks of resection as outlined in 
Section 6.4 and Table 6, and  
2. Those who are scheduled for resection of lung lesions in a stepwise fashion. Patients in this group will initiate 
treatment between resections as described in Section 6.4. Prior to resection all patients will receive the Hu5F9-G4 
(magrolimab)/dinutuximab as outlined in Table 6. If restart of Hu5F9-G4 (magrolimab)/dinutuximab occurs within 
four (4) weeks of the last dose of Hu5F9-G4 (magrolimab), the patient will pick up the regimen as per the next 
scheduled regimen cycle for a maximum of 5 cycles postoperatively. 
If the restart of the Hu5F9-G4 (magrolimab)/dinutuximab is delayed beyond four weeks of the last dose of Hu5F9-
G4 (magrolimab), the post-surgical regimen will be conducted as per Table 7and will require a re-priming dose of 
Hu59-G4 (magrolimab).  
 
Every attempt will be made to enroll to the “step-wise resection” subgroup prior to the first resection in order to obtain 
tissue from the resection for research correlatives. If subjects are enrolled after the initial resection, a request will be made 

                              
 
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for archived tissue for analysis. Within 4 weeks after the initial resection, patients will receive the priming dose of Hu5F9-
G4 (magrolimab) on Day 1, followed by Cycle 1 in week 2 with Hu5F9-G4 (magrolimab) administered at RP2D on Day 1 
and dinutuximab 17.5 mg/m2 on Days 2-5, followed by Hu5F9-G4 (magrolimab) at RP2D on Day 1 of weeks 3 and 4 until 
the second resection (see Table 6 below). Upon recovery from the second resection, the cycles may be repeated to a 
maximum of 5 cycles (adjuvant therapy). If the cycles are restarted within 4 weeks of the last dose of Hu5F9-G4 
(magrolimab), the patient will pick up the regimen as per the next scheduled regimen cycle as per Table 6. If restarting the 
regimen is delayed beyond 4 weeks of the last dose of Hu5F9-G4 (magrolimab), the patient will restart as per Table 7 and 
will require a re-priming dose of Hu59-G4 (magrolimab) with repeat of cycle 1 and 2 with weekly dosing of Hu5F9-G4 
(magrolimab). 
 
Table 6: Regimen Description for Arm B - Expansion Cohorts B1 – B3 (Confirmed Neuroblastoma, Evaluable 
Neuroblastoma, Measurable Osteosarcoma), Cohort B4 (Resectable, pulmonary only relapsed osteosarcoma**) - Non-
staged resections and Cohort B4 – Staged resections prior to surgery and post resection with restart within 4 weeks 
of last dose 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length 
Hu5F9-G4 
(magrolima
b) 
Administer according to 
guidelines 
in 
Section 
6.2.1.3. 
Acetaminophen 
oral 
(PO) 
and 
diphenhydramine (IV) or a 
comparable regimen up to 
15 minutes before the first 
two doses of Hu5F9-G4 
(magrolimab), and in case 
of re-priming of the patient 
after > 4 weeks interruption 
in treatment.  
 
Monitor 
for 
infusion 
reactions during and for 1-
hour post infusion during 
the priming dose. Any 
patients experience AEs 
during this period should be 
monitored 
as 
clinically 
indicates for up to 24 hours 
post infusion. Treatment of 
infusion reactions will be 
according 
to 
standard 
operating procedures. 
10 mg/kg (max 
650 
mg) 
of 
acetaminophen
; 0.5 - 1 mg/kg 
(max 50 mg) of 
diphenhydrami
ne^ 
Acetaminophen 
PO; 
Diphenhydramin
e IV 
Priming:  
Day 1 Week 1 
 
21 days  
(3 
weeks) 
 
 
 
Priming: 
Hu5F9-G4 
(magrolimab) 1 
mg/kg 
Priming: 
Infuse 
IV (peripheral or 
central line) over 
3 hours (± 30 
min) 
Cycles 
1-2: 
Hu5F9-G4 
(magrolimab) 
RP2D mg/kg* 
Subsequent 
infusions: Infuse 
IV over 2 hours  
(± 10 min) 
Cycle 1:  
Day 1, Weeks 
2, 3 and 4 
Cycle 2:  
Day 1, Weeks 
1, 2 and 3 
Cycle 3 and 
subsequent 
cycles: Day 1 
of Weeks 1 
and 3 of each 
cycle (Week 2 
is skipped)** 
Dinutuxima
b 
Administration 
requires 
premedication 
(acetaminophen 
- 
oral, 
diphenydramine -IV, and 
analgesia) and hydration 
prior to initiation according 
10 mg/kg (max 
650 
mg) 
of 
acetaminophen
; 0.5 - 1 mg/ kg 
(max 50 mg) of 
diphenhydrami
Acetaminophen 
PO 
Diphenhydramin
e^ IV (no need to 
be 
repeated 
if 
dinutuximab 
Cycles 
1 
(Week 
2): 
Days 2-5  
 
Subsequent 
cycles: 
Days 

                              
 
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to Section 6.2.1.4 
 
 
 
 
 
 
 
 
 
Administer 0.9% Sodium 
Chloride Injection USP 10 
mL/kg as an IV over 1 hour 
prior to initiating drug 
infusion 
ne^ 
 
Analgesia per 
section 6.2.1.4 
 
Dinutuximab - 
17.5 mg/m2 
immediate 
follows previous 
drug infusion) 
 
Analgesia 
as 
described below 
in 
Section 
6.2.1.4.  
Dinutuximab 
in 
100 mL bag of 
0.9% 
Sodium 
Chloride 
Injection 
USP 
(mix by gentle 
inversion- 
DO 
NOT shake) 
2-5 of the first 
week of each 
subsequent 
cycle 
*  Determined during dose finding cohort. 
** Cycles may be repeated as long as the patient does not have unacceptable toxicity (see Section 6.3 or Section 
Error! Reference source not found.) or disease progression to a maximum of 12 cycles (in Cohorts B1 through B3) 
or to a maximum of 5 cycles post resection (Cohort B4) 
^ Hydroxyzine (0.5-1 mg/kg, Max dose 50 mg) PO may substitute for diphenhydramine 
 
Table 7: Regimen Description for Arm B - Expansion Cohort B4 Staged Resection – Post Resection with Delayed 
Restart > 4 weeks (Resectable, pulmonary only relapsed osteosarcoma**) 
Post-Surgical resection for staged bilateral pulmonary metastases (regimen for at least 1 cycle prior to 
pulmonary metastesectomy) if restart delayed 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length 
Hu5F9-G4 
(magrolima
b) 
Administer according to 
guidelines 
in 
Section 
6.2.1.3. 
Acetaminophen 
oral 
(PO) 
and 
diphenhydramine (IV) or a 
comparable regimen up to 
15 minutes before the first 
two doses of Hu5F9-G4 
(magrolimab). 
 
Monitor 
for 
infusion 
reactions during and for 1-
hour post infusion during 
the priming dose. Any 
patients experience AEs 
during this period should be 
monitored 
as 
clinically 
indicates for up to 24 hours 
post infusion. Treatment of 
infusion reactions will be 
10 mg/kg (max 
650 
mg) 
of 
acetaminophen; 
0.5 - 1 mg/ kg 
(max 50 mg) of 
diphenhydramine^ 
Acetaminophe
n PO; 
Diphenhydrami
ne IV 
Post 
resection 
Priming: Day 1, 
Week 1 
 
21 days  
(3 
weeks) 
 
 
 
Post 
resection 
Priming: Hu5F9-
G4 (magrolimab) - 
1 mg/kg 
Priming: Infuse 
IV (peripheral 
or central line) 
over 3 hours (± 
30 min) 
Post 
resection 
Cycles 
1-2: 
Hu5F9-G4 
(magrolimab) 
RP2D mg/kg* 
Subsequent 
infusions: 
Infuse IV over 
2 hours (± 10 
min) 
Post resection  
Cycle 1: Day 1, 
Weeks 2, 3 and 4  
 
Post resection  
Cycle 2: Day 1 
of each week 
 

                              
 
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Page 56 
 
 
according 
to 
standard 
operating procedures. 
Post resection  
Cycle 
3 
and 
subsequent 
cycles: Day 1 of 
Weeks 1 and 3 
of each cycle 
(Week 
2 
is 
skipped) 
Dinutuxima
b 
Administration 
requires 
premedication 
(acetaminophen 
- 
oral, 
diphenydramine -IV, and 
analgesia) and hydration 
prior to initiation according 
to Section 6.2.1.4 
 
 
Administer 0.9% Sodium 
Chloride Injection USP 10 
mL/kg as an IV over 1 hour 
prior to initiating drug 
infusion 
10 mg/kg (max 
650 
mg) 
of 
acetaminophen; 
0.5 - 1 mg/ kg 
(max 50 mg) of 
diphenhydramine^ 
 
Analgesia 
per 
section 6.2.1.4 
 
Dinutuximab 
- 
17.5 mg/m2 
Acetaminophe
n PO 
Diphenhydrami
ne^ IV 
(no need to be 
repeated 
if 
dinutuximab 
immediate 
follows 
previous drug 
infusion) 
 
Analgesia 
as 
described 
below 
in 
Section 6.2.1.4.  
Dinutuximab in 
100 mL bag of 
0.9% 
Sodium 
Chloride 
Injection USP 
(mix by gentle 
inversion- DO 
NOT shake) 
Post 
resection 
Cycles 1 (Week 
2): Days 2-5;  
 
Subsequent Post 
resection cycles: 
Days 2-5 of the 
first 
week 
of 
each subsequent 
cycle 
*  Determined during dose finding cohort. 
** Patients who are scheduled for resection of lung lesion(s) unilateral or those who have recently undergone resection 
of lung lesion may continue the regimen for up to 5 cycles post resection in the absence of unacceptable toxicity or 
disease progression/recurrence. 
 ^ Hydroxyzine (0.5-1 mg/kg, Max dose 50 mg) PO may substitute for diphenhydramine 
 
6.2.1.3 
Clinical Care for Administration of Hu5F9-G4 (magrolimab) 
 
A priming dose of Hu5F9-G4 (magrolimab) is required on week 1, prior to starting therapy and upon restart of therapy if > 
four weeks occurs since the last dose of Hu5F9-G4 (magrolimab). The priming dose (1 mg/kg) will be infused over 3 hours 
(+/- 30 minutes) via a peripheral or central line. Protecting IV bag from light is not required. In-line IV filter set is not 
required. Subsequent IV doses can be infused over 2 hours (+/- 10 minutes). If Hu5F9-G4 (magrolimab) dosing is ever 
delayed for greater than 4 weeks, a re-priming dose must be administered on week one, with scheduled dosing restarted 1 
week later as depicted in Figure 2. 
 

                              
 
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Page 57 
 
 
Hu5F9-G4 (magrolimab) dose will be calculated using the actual body weight of the patient at enrollment (screening visit), 
and the dose may remain constant throughout the study unless a greater than 10% change in weight is observed. 
 
Hu5F9-G4 (magrolimab) may interfere with the assessment of RBC phenotyping. Hu5F9-G4 (magrolimab) binds to CD47 
on RBCs and can mask detection of antibodies to minor antigens to the patient’s RBC and ABO/Rh phenotype, DAT and 
Ab screen. Refer to section 7.2.4 for assessments to be performed and resulted prior to the administration of the priming 
dose.  
 
Anemia is a known and well described risk for Hu5F9-G4, which can occur in early doses and is transient.  
• 
Within 24 hours prior to the Priming dose (Week 1) of Hu5F9-G4 (magrolimab) infusion, all patients must have a 
documented hemoglobin level of ≥ 9.5 g/dL, per eligibility criterion 3.1.7.  
• 
Within 24 hours prior to the first full dose (Week 2) of Hu5F9-G4 (magrolimab) infusion, all patients must have a 
documented hemoglobin level of ≥ 9.0 g/dL.  
• 
Patients who do not meet these criteria must be transfused and have their hemoglobin rechecked to meet the 
minimum hemoglobin threshold, as noted above, prior to administrating each of the first 2 doses of Hu5F9-G4 
(magrolimab).  
• 
An additional hemoglobin must be checked 3 to 6 hours after the initiation of the first (Priming) and second (Week 
2) doses of Hu5F9-G4 (magrolimab). The patient should be transfused as clinically appropriate. Investigators should 
consider additional hemoglobin monitoring during the first week of treatment in patients with symptoms of anemia 
or at increased risk of complications of anemia.  
 
Men and women of reproductive potential must use effective contraception while receiving study treatment and for 4 months 
after the last dose of Hu5F9-G4 (magrolimab). Male patients whose partners are pregnant may continue study treatment and 
should use barrier method contraception (condom) to prevent exposing the fetus. Refer to Section 6.8 of for further details.  
 
Since infusion reactions can occur, all patients should be monitored pre-priming dose (within 30 minutes), every 30 minutes 
(±10) during priming dose infusion, for 1-hour post-infusion of the priming dose with vital signs (heart rate, respiratory 
rate, blood pressure, temperature, pulse oximetry) or as clinically indicated. Vital signs and AEs will be collected 30 (±10) 
minutes and 1 hour (±10 minutes) post-infusion. Patients who experience any treatment-related adverse events during the 
observation period should be further monitored as clinically appropriate (e.g., for up to 24 hours post-dose). All patients 
should be monitored with hourly (±20 minutes) vital signs during and for 1-hour (±20 minutes) post-infusion for Cycle 1. 
Further doses (Cycle 2+) do not require post-infusion observation, but hourly (±20 minutes) vital signs during the infusion. 
Patients who experience any treatment-related AEs during the observation period should be further monitored as clinically 
appropriate.  
 
6.2.1.4 
Clinical Care for Administration Dinutuximab (Unituxin®) 
 
Dinutuximab will be administered inpatient; ensure that cardiopulmonary resuscitation medications and equipment are 
available. Administer required premedication and hydration prior to initiation. Administer dose over 10-20 hours at an 
infusion rate initially at 0.875 mg/m2/hour for 30 minutes, or as per institutional guidelines. Infusion rates may be gradually 
increased as tolerated to a maximum rate of 1.75 mg/m2/hour, or as per institutional guidelines. The infusion duration may 
be extended up to 20 hours for anticipated toxicities (pain, fever, tachycardia, tachypnea, hypotension), not responding to 
other supportive measures, and the duration used should be recorded. The maximum infusion time is 20 hours; dinutuximab 
administration must be stopped after 20 hours even if the total dose has not been administered. The total dose given in 20 
hours should be recorded. 
 
• 
Analgesics for pain management  
 
Administer analgesia and opioids as per institutional guidelines. As recommended, morphine sulfate (50 mcg/kg) should be 

                              
 
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Page 58 
 
 
administered intravenously immediately prior to initiation of dinutuximab and then continue as a morphine sulfate drip at 
an infusion rate of 20 to 50 mcg/kg/hour titrated to effect during and for two hours following completion of dinutuximab, 
as per institutional guidelines. 
 
Administer additional 25 mcg/kg to 50 mcg/kg intravenous doses of morphine sulfate as needed for pain up to once every 
2 hours followed by an increase in the morphine sulfate infusion rate in clinically stable patients, or as per institutional 
guidelines.  
 
Consider using fentanyl or hydromorphone if morphine sulfate is not tolerated, as per institutional guidelines. 
 
If pain is inadequately managed with opioids or to reduce opiate requirements during dinutuximab therapy, consider use of 
gabapentin or lidocaine in conjunction with intravenous morphine or as per institutional guidelines. 
 
To optimize the effect of gabapentin, it should be initiated 1 week prior to expected start of antibody so that it can be 
increased to full dose by the start of dinutuximab administration. Dosing should follow institutional standards; however, the 
following dosing may be considered:  
• 
Day 1: 5 mg/kg/dose (max 300 mg/dose) at bedtime  
• 
Day 2: 5 mg/kg/dose (max 300 mg/dose) BID  
• 
Day 3: 5 mg/kg/dose (max 300 mg/dose) TID – patients should be at this dose by the time of admission for 
cycle 1 dinutuximab  
• 
Gabapentin doses can be increased further if necessary; institutional guidelines should be followed.  
 
Lidocaine dosing should follow institutional standards; however, the following dosing may be considered: 
• 
Initiate continuous infusion at 1 mg/kg/hour (bolus) with the continuous infusion rate of is 0.5 -2 mg/kg/hour.  
• 
Lidocaine levels should initially be checked every 8 hours (Q8h) but may be spaced out once therapeutic 
concentrations have been achieved.  Dose should be titrated in 25% increments to achieve therapeutic serum 
concentrations (goal 2-4 mcg/mL). 
• 
Consider dose reduction in patients with hepatic disease. 
 
• 
Premedications for infusion reactions 
 
o Antihistamines and Antipyretics  
 
Administer an antihistamine such as diphenhydramine (0.5 to 1 mg/kg; maximum dose 50 mg) intravenously over 10 to 15 
minutes starting 20 minutes prior to initiation of dinutuximab and as tolerated every 4 to 6 hours during the dinutuximab 
infusion, as per institutional guidelines.  
 
o Acetaminophen 
 
Administer acetaminophen (10 to 15 mg/kg/dose; maximum dose 650 mg) PO approximately 20 minutes prior to each 
dinutuximab infusion and every 4 to 6 hours as needed for fever or pain, or as per institutional guidelines.  
 
o Ibuprofen 
 
Administer ibuprofen (5 to 10 mg/kg/dose) every 6 hours as needed for control of persistent fever or pain, as per institutional 
guidelines.  
 
• 
Monitoring Procedures 
 

                              
 
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Vital signs (heart rate, respiratory rate, blood pressure, temperature, pulse oximetry) will be collected prior to the beginning 
of dinutuximab infusion (within 30 minutes) and every 30 (±10) minutes for the first hour of infusion, and then hourly 
during infusion, or as clinically indicated. Post-infusion, vital signs and AEs will be collected every 30 (±10) minutes twice, 
then hourly (±20) minutes for a total of 4 hours. For patients who previously tolerated the study agent without infusion-
related reactions, the post-infusion monitoring period may be reduced at the discretion of and documented by the treating 
physician. 
 
Document intake and output on the day of dinutuximab administration. 
 
Standard imaging will be performed for disease assessment where indicated and according to the protocol schedule 
(screening, disease assessment at the conclusion of Cycle 2 and 4 and then every 4 cycles) (see Section 11).   
 
6.3 
Definition of Dose-Limiting Toxicity 
 
Adverse events that occur within the first 21 days of the ‘single agent Lead-In’ dosing of Hu5F9-G4 (magrolimab) or during 
the 21 days of Cycle 1 during the combination Hu5F9-G4 (magrolimab) and dinutuximab drug infusions, are at least 
possibly related to at least 1 study agent, and are ≥ Grade 3 in severity will be considered DLTs with the following additional 
criteria or exceptions: 
 
Hematologic Toxicity:  
• 
Anemia is an expected toxicity of Hu5F9-G4 (magrolimab) and dinutuximab, especially in patients who have had 
extensive prior therapy with chemotherapy, and therefore anemia and a need for blood transfusions will not be 
considered a DLT. Grade 3 hemolytic anemia that is medically significant, requires hospitalization or prolongation 
of existing hospitalization, is disabling, or limits self-care activities of daily life (ADLs) will be considered a DLT. 
 
• 
Thrombocytopenia can be expected in this heavily pretreated population who have had extensive prior therapy with 
chemotherapy, and therefore platelet count decreased in the absence of hemorrhage will not be considered a DLT 
unless < 25,000/mcL for > 14 days despite supportive care. 
 
• 
Grade 3 or 4 lymphopenia or leukopenia not associated with other clinically significant consequences. 
 
Non-hematological Toxicity:  
• 
Any Grade 3 or greater, non-hematological toxicity will be considered a DLT with the following exceptions:  
 
a. 
Pain and sensory neuropathy are expected toxicities of dinutuximab, but pain or sensory neuropathy at 
levels described in Table 8: Adverse Reactions Requiring Permanent Discontinuation of Dinutuximab 
will be considered a DLT. Pain requiring sedation and respiratory support for control will also be considered 
a DLT. 
b. 
Tumor lysis syndrome, including associated abnormalities (e.g., electrolytes, uric acid, renal function).  
c. 
Grade 3 low electrolyte levels that are correctable and asymptomatic.  
d. 
Grade 3 hypoalbuminemia. Such individuals should receive supplementation as indicated. Hypocalcemia 
toxicity grade should be assigned based on the calcium level corrected for degree of hypoalbuminemia 
according to the following formula: for every albumin decrease of 1 gm/dL a total calcium increase of 0.2 
mmol/L is to be made.  
e. 
Grade 3 transaminase, alkaline phosphatase, bilirubin or other liver function test elevation, provided there 
is resolution to ≤ grade 2 with supportive care within 7 days and is not associated with other clinically 

                              
 
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significant consequences. Grade 3 transaminase elevation, alkaline phosphatase or hyperbilirubinemia 
elevation of any duration in patients with liver involvement due to tumor will not be considered a DLT, 
although Grade 4 hepatic toxicity will be considered DLT. 
f. 
Transient Grade 3 nausea, vomiting, diarrhea, local reactions, influenza-like symptoms, myalgias, fever, 
headache, acute pain, or skin toxicity that resolves to ≤Grade 2 within ≤72 hours after medical management 
(e.g., supportive care, including immunosuppressant treatment) has been initiated. 
g. 
Grade 3 fatigue that resolves to ≤Grade 2 within 1 week. 
h. 
Grade 3 infusion reactions in the absence of an optimal pretreatment regimen, which is defined as 
acetaminophen or a comparable non-steroidal anti-inflammatory agent, plus an antihistamine and 
corticosteroids. 
i. 
Grade 3 or 4 infection or neutropenic fever although Grade 4 infection uncontrolled for > 7 days will be 
considered DLT.  
j. 
Grade 3 electrolyte disturbances (hyperkalemia, hypophosphatemia, hyperuricemia, etc.) that resolves to 
≤Grade 2 or baseline within 1 week. Grade 4 hyponatremia not responsive to appropriate fluid management 
for dinutuximab will be considered a DLT. 
k. 
Other single laboratory values out of normal range that have no clinical correlate and resolve to Grade ≤1 
or to baseline within 7 days with adequate medical management. 
l. 
Tumor flare phenomenon defined as local pain, irritation, or rash localized at sites of known or suspected 
tumor. 
m. 
Grade 3 decrease in vision that resolves to grade 1 or better before the next dose dinutuximab will not be 
considered a DLT and dose will be modified as per Section 7.3.2. Eye disorders such as sluggish light reflex 
or other visual disturbances that do not cause visual loss will not be considered DLT. Subtotal or total vision 
loss will be considered a DLT. 
n. 
Capillary leak syndrome and/or hypotension (grade 3-4) which resolves to ≤Grade 2 or baseline within 8 
hours with maximum supportive care.  
 
Management and dose modifications associated with the above adverse events are outlined in Section 7. 
 
6.4 
Dose Expansion Cohorts 
 
Upon determining RP2D, enrollment to 4 expansion cohorts will proceed to evaluate evidence of clinical activity (cohorts 
B1-3) and safety/feasibility of using this combination drug approach after surgery (cohort B4) (Figure 2).  
 
Cohort B1 – Confirmed neuroblastoma: measurable neuroblastoma/ganglioneuroblastoma 
Cohort B2 – Evaluable neuroblastoma 
Cohort B3 – Measurable osteosarcoma 
Cohort B4 – Resectable, pulmonary only relapsed osteosarcoma 
 
All subjects will receive the priming dose of 1 mg/kg Hu5F9-G4 (magrolimab) on Day 1 of week 1. On Day 1 of week 2, 
subjects will receive Hu5F9-G4 (magrolimab) at RP2D followed by 17.5 mg/m2 dinutuximab IV on Days 2-5. Then, they 
will receive Hu5F9-G4 (magrolimab) at RP2D on Day 1 of week 3 and week 4 (Figure 2 and Section 6.2.1.2).   
 
Cycle 2 will consist of Hu5F9-G4 (magrolimab) at RP2D on Day 1 of week 1 in combination with 17.5 mg/m2 dinutuximab 
IV given on Days 2-5, followed by Hu5F9-G4 (magrolimab) at RP2D on Day 1 of weeks 2-3 (see Figure 2 and Section 
6.2.1.2). A disease evaluation will be conducted after Cycle 2 and Cycle 4, and then after every 4 cycles (every 12 weeks) 
until progressive disease or a maximum of 12 cycles (except cohort four which will have a maximum of five cycles after 
the patient is rendered No Evidence of Disease (NED)). After Cycle 2, each subsequent cycle will consist of Hu5F9-G4 

                              
 
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(magrolimab) administered on Day 1 of weeks 1 and 3 of the cycle (week 2 will be a week of rest), with dinutuximab 
administration on Day 2-5 of week 1. 
 
Cohort B4 will consist of some patients who will undergo a unilateral thoracotomy for removal of metastatic lesions which 
will render them NED. Those patients will begin therapy when deemed safe by clinical judgement of the treating 
physician/surgeon. These patients will receive the priming dose of 1 mg/kg Hu5F9-G4 (magrolimab) on Day 1 of week 1, 
followed by Hu5F9-G4 (magrolimab) at RP2D on Day 1 of week 2 in combination with 17.5 mg/m2 dinutuximab IV given 
on Days 2-5, followed by Hu5F9-G4 (magrolimab) at RP2D on Day 1 of weeks 3-4 for Cycle 1 (see Figure 2 and Section 
6.2.1.2). Cycle 2 will consist of Hu5F9-G4 (magrolimab) at RP2D on Day 1 of week 1 in combination with 17.5 mg/m2 
dinutuximab IV given on Days 2-5, followed by Hu5F9-G4 (magrolimab) at RP2D on Day 1 of weeks 2-3 (see Figure 2). 
A disease evaluation will be carried out after 2 cycles and then after 5 cycles until progressive/recurrent disease. After Cycle 
2, Hu5F9-G4 (magrolimab) will be administered at RP2D on Day 1 of weeks 1 and 3 of cycles 3 – 5 (week 2 will be a week 
of rest) with dinutuximab administration on Day 2-5 of week 1 in each cycle. Patients on Cohort B4 will receive a maximum 
of five cycles after the patient is rendered NED. 
 
Cohort B4 will also consist of other patients scheduled for staged thoracotomy who will receive the Priming Dose and Cycle 
1 within 4 weeks after the initial resection of pulmonary disease. Upon completion, as per previously scheduled, the patient 
will undergo the second thoracotomy, and subsequently resume Cycle 2 of Hu5F9-G4 (magrolimab)/dinutuximab when 
deemed safe by clinical judgement of the treating physician. Cycle 2 will consist of Hu5F9-G4 (magrolimab) at RP2D on 
Day 1 of week 5 in combination with 17.5 mg/m2 dinutuximab IV given on Days 2-5, followed by Hu5F9-G4 (magrolimab) 
at RP2D on Day 1 of weeks 2-3 (see Figure 2). A disease evaluation will be carried out after 2 cycles (i.e., end of Cycle 3) 
and then after 5 cycles (i.e., end of Cycle 6) until recurrent disease (see Section 12). After Cycle 2 in the post-surgical 
regimen, Hu5F9-G4 (magrolimab) will be administered at RP2D on Day 1 of weeks 1 and 3 of cycles 3 – 5 (2nd week will 
be a week of rest) with dinutuximab administration on Days 2-5 of week 1 in each cycle. Patients on Cohort B4 may receive 
a maximum of five cycles after their second surgical resection. 
 
Doses of Hu5F9-G4 (magrolimab) and dinutuximab in the expansion cohorts may be interrupted, delayed or discontinued 
depending on how well the participant tolerates the treatment. Dosing visits are not skipped, only delayed. Both Hu5F9-G4 
(magrolimab) and dinutuximab must be delayed at the same time. Protocol therapy must be discontinued for dose delays 
greater than 14 days except for reasons outlined in Section 6.6. In such cases, the Protocol Principal Investigator must be 
consulted prior to resuming treatment.  
 
For the expansion cohorts, patients will continue to be monitored for occurrence of DLT during Cycle 1. If 2 of the first 5 
patients or if ≥2 of 6 patients experience DLT, the Principal Investigator will discuss with all study investigators and with 
CTEP whether further addition of patients is needed to re-assess the RP2D. 
 
Monitoring of all safety and toxicity data is done by the Principal Investigator and the Corresponding Organization on a 
real-time basis as data are entered into Medidata Rave using the Web Reporting Module. All participating sites are expected 
to notify the Principal Investigator when a DLT has occurred. 
 
6.5 
Criteria for Removal from Protocol Therapy and Off Study Criteria 
 
6.5.1 
Criteria for Removal from Protocol Therapy 
 
In the absence of treatment delays due to adverse event(s), treatment may continue for to a maximum of 12 cycles (9 months 
of combination therapy) [except in cohort B4, resectable, pulmonary only relapsed osteosarcoma, who may continue 
combination therapy for a total of 5 cycles after pulmonary resection] or until one of the following criteria applies: 
 
• 
Disease progression 

                              
 
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• 
Intercurrent illness that prevents further administration of treatment. 
• 
Unacceptable adverse event(s), including, but not limited to, any one of the following: 
o Patients who have Grade 4 infusions reactions occurring with the first dose of Hu5F9-G4 (magrolimab) or 
dinutuximab will be permanently discontinued from treatment. 
o Patients who receive Hu5F9-G4 (magrolimab) premedication with corticosteroids and still have a Grade 3 or 4 
infusion reaction on subsequent doses will generally be permanently discontinued from treatment, unless continued 
therapy is approved by the Study PI, Site PI and Sponsor. 
o Patients who receive dinutuximab and experience any of the AEs listed in Table 8: Adverse Reactions Requiring 
Permanent Discontinuation of Dinutuximab 
or recur after appropriate management as outlined in Section 7.3.2. 
• 
Patient who develops a DLT during the “single agent Safety Lead-In” will be removed from additional therapy on this 
study. 
• 
General or specific changes in the patient's condition render the patient unacceptable for further treatment in the 
judgment of the investigator. 
• 
Clinical progression of disease 
• 
Patient non-compliance 
• 
Pregnancy 
o All women of childbearing potential should be instructed to contact the investigator immediately if they suspect 
they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. 
o The investigator must immediately notify CTEP in the event of a confirmed pregnancy in a patient participating 
in the study. 
• 
Termination of the study by sponsor 
• 
The drug manufacturer(s) can no longer provide the study agents. 
 
6.5.2 
Off Study Criteria 
a) Thirty days after the last dose of the investigational agent for patients who develop disease progression during 
combination therapy. 
b) The fifth anniversary of the date the patient was enrolled on this study, or until disease progression, for patients 
who complete the maximum number of cycles or who met off protocol therapy criteria in Section 6.5.1 other than 
disease progression.  
c) Withdrawal of consent for any required observations or data submission. 
d) The patient does not receive protocol treatment after study enrollment.  
e) Patient enrollment onto another COG study with therapeutic (anti-cancer) intent. 
f) Lost to follow-up. 
g) Death 
 
The reason(s) for removal from protocol therapy, the reason(s) for the patient being off study, and the corresponding dates 
must be documented in the Case Report Form (CRF). 
 
6.6 
Duration of Follow-Up 
Patients who complete the maximum number of cycles or who met off-therapy criteria other than disease progression will 
be asked to participate in study follow-up and be evaluated at month 2 (± 1 week), month 4 (± 2 weeks), month 6 (± 4 
weeks), month 9 (± 4 weeks), and month 12 (± 2 months) and then yearly until year 5, or until disease progression. 
 
Follow-up visits will be completed in-person unless the patient does not agree to continue in-person visits. In this case, 
telephone contact may be arranged to ensure the collection of as many safety and efficacy parameters as possible. The 
approach taken should be recorded in the CRF. A patient that agrees to modified follow-up is not considered to have 
withdrawn consent or to have withdrawn from the study.  

                              
 
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Patients who develop disease progression during combination therapy will be followed for a minimum of 30 days after the 
last dose of study drug or study procedure, or until death, whichever occurs first. Patients removed from study for 
unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event and disease progression, 
whichever occurs later. 
 
6.7 
General Concomitant Medication 
 
Medications, including reason for use, date(s) of administration, and dosage information, taken within 28 days prior to the 
start of treatment will be recorded. Concomitant medications, including medications for AEs, will continue to be recorded 
up to 30 days after treatment discontinuation. This includes any medication or vaccine, including over-the-counter or 
prescription medicines, vitamins, and/or herbal supplements. The investigator should be alerted if the patient is taking any 
agent known to affect the study agent(s) or with the potential for drug interactions. Following treatment discontinuation, 
information on subsequent anti-cancer therapies will be recorded. 
 
Because there is a potential for interaction of Hu5F9-G4 (magrolimab) and Dinutuximab with other concomitantly 
administered drugs, the case report form must capture the concurrent use of all other drugs, over-the-counter medications, 
or alternative therapies. The Principal Investigator should be alerted if the patient is taking any agent known to affect or 
with the potential for drug interactions. The study team should check a frequently updated medical reference for a list of 
drugs to avoid or minimize use of.  
 
For all prohibited and/or restricted concomitant medications, treatment and supportive care while receiving protocol therapy, 
please refer to inclusion/exclusion criteria (section 3.0).  
Pharmacologic doses of systemic corticosteroids should be used ONLY for life-threatening conditions (i.e. life-threatening 
allergic reactions and anaphylaxis such as bronchospasm, stridor) unresponsive to other measures. The use of 
dexamethasone as an anti-emetic is not permitted. Corticosteroid therapy can be used as a premedication for transfusion 
in patients known to have a history of transfusion reactions or for treatment of an unexpected transfusion reaction 
(hydrocortisone 2 mg/kg or less or an equivalent dose of an alternative corticosteroid). The use of steroids during protocol 
therapy requires clear justification and documentation.  
 
Patients who use oral contraceptives should continue their use. Males and females of reproductive potential should use 
highly effective means of contraception (refer to section 6.8). 
 
6.7.1 
Hu5F9-G4 (magrolimab) Excluded Therapies 
 
Any concomitant therapy intended for the treatment of cancer, whether health authority approved or experimental, is 
prohibited unless it is specifically included in the treatment regimen described in this protocol. There are no studies 
regarding drug-drug interactions conducted with Hu5F9-G4 (magrolimab). 
 
6.7.2 
Dinutuximab Excluded Therapies 
 
Any concomitant therapy intended for the treatment of cancer, whether health authority approved or experimental, is 
prohibited unless it is specifically included in the treatment regimen described in this protocol. There are no studies 
regarding drug-drug interactions conducted with dinutuximab. 
 
6.8 
Contraception 
 
The effects of Hu5F9-G4 (magrolimab) monoclonal antibody on the developing human fetus are unknown and dinutuximab 
is known to be teratogenic.  

                              
 
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A woman is of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous 
months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal 
of ovaries and/or uterus). 
 
Females of childbearing potential must have a negative urine or serum pregnancy test within 30 days of enrollment and 
within 72 hours prior to treatment initiation. Additional pregnancy tests (serum or urine) should be obtained throughout the 
study in accordance with local policy. 
 
Female patients of childbearing potential must be willing to use one highly effective method of contraception (hormonal or 
barrier method of birth control; abstinence) prior to study entry, during the study and continue for 4 months after the last 
dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating 
in this study, she should inform her treating physician immediately. 
 
• 
Examples of contraceptive methods with a failure rate of < 1% per year include: bilateral tubal ligation, male 
sterilization, and established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing 
intrauterine devices, and copper intrauterine devices.  
• 
Hormonal contraceptive methods must be supplemented by a barrier method plus spermicide.  
• 
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred 
and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception. 
 
Male patients who are sexually active with a woman of childbearing potential (WOCBP) and who have not had vasectomies 
must be willing to use a barrier method of contraception (condom plus spermicidal gel) and refrain from sperm donation 
during the study and for 4 months after the last dose of study treatment. If the partner is pregnant, male patients must use 
barrier method contraception (condom) during the study and for 4 months after the last dose of study treatment to prevent 
fetal exposure to study treatment. 
 
7 
DOSING DELAYS/DOSE MODIFICATIONS 
 
The administration of Hu5F9-G4 (magrolimab) (in the “single agent Safety Lead-In” and/or during cycles of the 
combination cycles with Hu5F9-G4 (magrolimab) and dinutuximab) will be modified according to the attribution (possibly, 
probably or definitely related) to either Hu5F9-G4 (magrolimab) or dinutuximab. 
 
The National Cancer Institute (NCI) CTCAE Version 5.0 will be used to grade AEs. Patients enrolled in this study will be 
evaluated clinically and with standard laboratory tests before and at regular intervals during their participation in this study 
as specified in this section. 
Patients will be evaluated for AEs (all grades), SAEs and AEs requiring study drug interruption or discontinuation at each 
study visit for the duration of their participation in the study. 
 
The primary approach to mild AEs (Grades 1−2) is supportive and symptomatic care. The general approach to clinically 
significant and/or unacceptable toxicity (Grade 3 AEs) is holding study treatment until the toxicity resolves (≤ Grade 2) and 
then resume at one dose level lower, if clinically indicated. Supportive therapy must be administered per standard clinical 
practice.  Consultation with the protocol PI and/or the PED-CITN Coordinating Center is required.  
 
Adverse Event specific guidelines are provided below.  
 

                              
 
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7.1 
Dosage modification for Hu5F9-G4 (magrolimab) 
 
Nausea 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1. Resume at same dose level. 
Grade 3 
Hold until < Grade 2. Resume at one dose level lower, if indicated.* 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
Recommended management: antiemetics 
 
Vomiting 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1. Resume at same dose level. 
Grade 3 
Hold until < Grade 2. Resume at one dose level lower, if indicated.* 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
Recommended management: antiemetics 
 
Diarrhea 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1. Resume at same dose level. 
Grade 3 
Hold until < Grade 2. Resume at one dose level lower, if indicated.* 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
Recommended management: Loperamide antidiarrheal therapy with dosage schedule: 4 mg at first onset, 
followed by 2 mg with each loose motion until diarrhea-free for 12 hours (maximum dosage: 16 mg/24 
hours) 
Adjunct anti-diarrheal therapy is permitted and should be recorded when used. 
 
Neutropenia 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
≤ Grade 1 
No change in dose 
Grade 2 
No change in dose. 
Grade 3 
No change in dose.  
Grade 4 
Hold until ≤ Grade 2. Resume at same dose level.*  
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Thrombocytopenia 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
≤ Grade 1 
No change in dose 
Grade 2 
No change in dose.  
Grade 3 
Hold until ≤ Grade 2. Resume at same dose level. * 
Grade 4 
Hold until ≤ Grade 2. Resume at one dose level lower, if indicated. * 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Anemia 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
≤ Grade 1 
No change in dose 
Grade 2 
No change in dose 
Grade 3 hemolytic anemia that is  

                              
 
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Anemia 
Management/Next Dose for Hu5F9-G4 (magrolimab) 
medically 
significant 
(requiring 
hospitalization or prolongation of 
existing hospitalization, disabling, or 
limiting self-care ADLs) 
First occurrence: Reduce by 1 dose level.  
• 
If recurs after 1 dose level reduction: permanently 
discontinue unless patient is clinically benefitting. 
 
Grade 4 
First occurrence: permanently discontinue unless patient is 
clinically benefitting. 
 
7.2 
Hu5F9-G4 (Magrolimab) AE Management and Dose Interruption Guidelines  
 
For detailed information regarding management of AEs associated with Hu5F9-G4 (magrolimab), please refer to the most 
current version of the Hu5F9-G4 (magrolimab) Investigator’s Brochure. 
 
7.2.1 
Management of Infusion-related Reactions (IRR) 
 
The most common adverse events associated with IRRs include chills, pyrexia, back pain, nausea, vomiting, hypotension, 
dyspnea, and headache. These primarily occur with the first two doses of Hu5F9-G4 (magrolimab), and are mostly observed 
during the infusion or several hours afterward.  
 
Preventive Measures 
 
Premedication should include oral acetaminophen and an antihistamine (IV or oral) before the first two doses of Hu5F9-G4 
(magrolimab) or in case of re-priming of Hu5F9-G4 (magrolimab), please refer to Table 5.  
 
Recommendations for the management of IRRs are provided below. 
 
Toxicity 
Severity 
Management 
Infusion-related 
Reactions 
Grade 1 – mild 
transient reaction 
 
Remain at bedside and monitor patient until recovery from 
symptoms. 
Grade 2 - infusion 
interruption 
is 
indicated, 
but 
patient responds 
promptly 
to 
symptomatic 
treatment 
(e.g., 
antihistamines, 
non-steroidal 
anti-inflammatory 
drugs, narcotics, 
corticosteroids, 
IV fluids); and 
prophylactic 
medications 
are 
indicated 
for 
≤24 hours 
Stop the Hu5F9-G4 (magrolimab) infusion, begin an intravenous 
(IV) infusion of normal saline, and consider treating the patient with 
diphenhydramine (0.5 – 1 mg/kg, max 50 mg) IV (or equivalent) 
and/or 10 mg/kg, max dose 650 mg oral acetaminophen. 
Remain at bedside and monitor patient until resolution of 
symptoms. 
Corticosteroid therapy may also be given 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 occur after 1 hour (± 10 minutes), the 
rate may be increased to 100% of the original infusion rate. Monitor 
the patient closely. 
If symptoms recur, stop infusion and disconnect patient from the 
infusion apparatus. No further Hu5F9-G4 (magrolimab) will be 

                              
 
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Toxicity 
Severity 
Management 
administered at that visit. 
Premedications should be considered before any future infusions. 
The amount of Hu5F9-G4 (magrolimab) infused must be recorded 
on the case report form (eCRF). 
Patients who experience a grade 2 IRR during the post-infusion 
observation period that does not resolve during that time should be 
observed until the AE resolves, with vital sign measurements as 
medically indicated for the management of the AE. 
 
Grade 
3 
– 
prolonged 
infusion 
related 
reactions 
(e.g., 
not 
rapidly 
responsive 
to 
symptomatic 
medication and/or 
brief interruption 
of infusion), or 
recurrence 
of 
symptoms 
following 
initial 
improvement, or 
where 
hospitalization is 
indicated for other 
clinical sequelae 
(e.g., 
renal 
impairment, 
pulmonary 
infiltrates)  
 
or  
 
Grade 4 - having 
life-threatening 
consequences and 
where 
urgent 
intervention 
indicated) 
Immediately discontinue infusion of Hu5F9-G4 (magrolimab). 
Begin an IV infusion of normal saline, and consider treating the 
patient 
as 
follows: 
Administer bronchodilators, epinephrine 0.01 mg/kg up to 0.5 mg 
of a 1:1,000 solution for subcutaneous administration or 0.01 mg/kg 
of a 1:10,000 solution injected slowly for IV administration and/or 
diphenhydramine 0.5 – 1 mg/kg IV with methylprednisolone 1 
mg/kg IV (or equivalent), as needed. 
The patient should be monitored until the Investigator is 
comfortable that the symptoms will not recur. 
Patients who have grade 4 IRRs occurring with the first dose 
(priming dose) will be permanently discontinued from study 
treatment. 
Patients who experience grade 3 IRRs must be given premedication 
prior to all subsequent doses. In this setting, premedication with oral 
acetaminophen (10 mg/kg, max dose 650 mg), oral or IV 
diphenhydramine (0.5 – 1 mg/kg, max dose 50 mg), and IV 
dexamethasone (0.6 mg/kg), or a comparable regimen, is 
recommended for the subsequent 2 doses. Continued premedication 
with corticosteroids beyond these 2 doses may be administered at 
the discretion of the treating physician. 
Patients who receive premedication with a corticosteroid and still 
experience a grade 3 or 4 infusion-related reaction will be 
permanently discontinued from study treatment. 
Investigators should follow their institutional guidelines for the 
treatment of anaphylaxis. 
All patients with grade 3 or greater IRRs will be observed until the 
AE(s) resolves or stabilizes, with vital sign measurements and 
additional evaluations, as medically indicated for the management 
of the AE(s). 
In the case of late-occurring hypersensitivity symptoms (e.g., appearance of localized or generalized pruritus after Day 1 
but within 1 week after treatment), symptomatic treatment may be given (e.g., oral antihistamine or corticosteroids). 

                              
 
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7.2.2 
Magrolimab Dosing Guidance for Planned Surgical Procedures 
 
 
7.2.3 
Hemagglutination and Microangiopathy 
 
In the phase 1 trial experience with Hu5F9-G4 (magrolimab) in solid tumors and AML, agglutination of RBCs has been 
observed on peripheral smear. Hu5F9-G4-related microangiopathy is a possible sequela of hemagglutination; however, it 
has not been observed in the ongoing phase 1 clinical trials to date. In addition, AEs may be associated with findings of 
hemagglutination. Monitoring of hemagglutination and microangiopathy includes physical exam assessments, complete 
blood counts (CBCs), and serum chemistries testing as outlined in the schedule of assessments (SOA).  
 
7.2.4 
Anemia, Blood Cross-Matching, and Red Blood Cell Transfusion Procedures 
 
Hemoglobin level must be documented as detailed in section 6.2.1.3. Patients with a low baseline hemoglobin level, 
especially those with cardiac history or risk factors, must be monitored closely after initial administrations of Hu5F9-G4 
(magrolimab) as preexisting anemia can be exacerbated.   
Hu5F9-G4 (magrolimab) binds to red cells and leads to erythrophagocytosis. This, coupled with anemia from other causes 
in patients with cancers, means that care must be taken with RBC cross-matching and packed red blood cell (PRBC) 
transfusions. There is a possibility that treatment with Hu5F9-G4 (magrolimab) may obscure assessment of RBC 
phenotyping. 
• 
During the Screening Period prior to initiation of Hu5F9-G4 (magrolimab) therapy, blood cell ABO phenotyping for 
minor antigens, type and screen (ABO/Rh), and Direct Antiglobulin Test (DAT) will be performed for each patient. 
This, together with using the prior phenotype, will facilitate allocation of properly cross-matched blood, should a blood 
transfusion be warranted. 
 
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 3 days after. 
Moderately invasive procedure 
(Examples: 
 
lung/liver 
biopsy, 
hysterectomy, 
cholecystectomy, 
hip/knee 
replacement, 
minor 
laparoscopic procedures, stent/angioplasty) 
Hold magrolimab dose 5 days prior to 
procedure and restart 5 days after. 
Highly invasive procedure 
(Examples:  CNS/spine surgery, major vascular surgery, 
cardiothoracic surgery, major laparoscopic surgery) 
Hold magrolimab dose 7 days prior to 
procedure and restart 7 days after. 
Abbreviations: CNS = central nervous system 

                              
 
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Before Exposure to Hu5F9-G4 (magrolimab) 
In participants who have not been transfused in the preceding 3 months, an extended RBC 
phenotyping including minor antigens (Rh CcDEe, Cw, MNSs, K [k if K+] Fya, Fyb, Jka, 
and Jkb) should be performed at screening. In these participants, blood genotyping (that 
includes minor antigens Rh CcDEe, Cw, MNSs, K [k if K+] Fya, Fyb, Jka, and Jkb) is 
acceptable as an alternative to extended phenotyping. 
 
Because transfused blood can interfere with RBC phenotyping assessment, participants who 
received blood transfusion in the preceding 3 months should have their blood genotype 
documented at screening, and for these participants extended RBC phenotyping is not 
sufficient and does not need to be performed. 
Results should be available before the first dose of magrolimab.  
Procedure for patients after exposure to Hu5F9-G4 (magrolimab) 
In case ABO/Rh type cannot be resolved, use pretreatment phenotype/genotype matched units for ABO, Rh and other minor 
RBC antigens (CcDEe and Kk, to the feasible extent).  
 
7.2.5 
Blood Components for Transfusion 
 
For all elective red cell transfusions, leukocyte-reduced units matched for the phenotype of the patients (as described above) 
will be used.  Where exact matching for all the specified blood groups proves impractical (e.g., for any of the blood groups 
M, N, and S compromising the MNS system [MNS]), local sites will decide on the best matched donor units to be used.  
Cytomegalovirus (CMV) matching (i.e., CMV seronegative units for CMV-seronegative patients) will not be required for 
this study because it will limit the inventory for antigen matching. 
 
If the cross-match is incompatible, the RBC units that are Coomb's crossmatch-incompatible will be selected (e.g., 
phenotype-matched or least incompatible) for issue at the discretion of the local site’s Transfusion Service Medical Director 
or equivalent person, where available. Such instances will be documented, along with consent signatures obtained from 
ordering physicians, according to best practices in blood bank policies and procedures. 
For emergency transfusions, the transfusion laboratory may consider using emergency Group O Rhesus negative units if 
phenotyped units are not available. 
Blood plasma therapy will be blood-type specific. Platelets will be blood type compatible whenever possible, and if not, 
will have been tested and found not to have high titer anti-A or anti-B. 
 
7.2.6 
Management of Pneumonitis 
 
Pneumonitis has been infrequently observed in patients receiving magrolimab. It is currently unknown if Hu5F9-G4 
(magrolimab) increases the risk of pneumonitis.   
In instances of suspected pneumonitis, first rule out non-inflammatory causes (e.g., infections, etc.). If a non-inflammatory 
cause is identified, treat accordingly and continue therapy per protocol. Evaluate with imaging, e.g. chest x-ray or computed 
tomography, and pulmonary consultation. 
Management of potential pneumonitis is detailed below and follows American Society of Clinical Oncology (ASCO) 
guidelines for immune-related adverse events (Brahmer et al., 2018). Patients who experience Grade 3-4 pneumonitis will 
be permanently discontinued from study treatment. 

                              
 
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Pneumonitis 
CTCAE 
Grade 
of 
Pneumonitis 
Management 
Follow-Up 
Grade 
1 
Radiographic changes (CXR 
or CT) only. 
Monitor for signs and symptoms weekly and 
consider monitoring with CXR. 
Consider pulmonary and infectious disease 
consults. 
Consider re-imaging with CT in 3-4 weeks as 
clinically indicated. 
May resume magrolimab with radiographic 
evidence of improvement or resolution. 
If no clinical improvement or worsening, treat 
as Grade 2.  
Grade 
2 
Mild 
to 
moderate 
new 
symptoms. 
Interrupt magrolimab therapy per protocol. 
Pulmonary and infectious disease consults. 
Consider empirical antibiotics. 
Monitor signs and symptoms every 2-3 days; 
consider hospitalization. 
1 mg/kg/day oral prednisone or IV equivalent. 
Consider bronchoscopy, lung biopsy. 
Re-image every 1-3 days. 
If improving to baseline, taper corticosteroids 
over 4-6 weeks and resume magrolimab 
therapy per protocol. 
If no clinical improvement after 48-72 hours or 
worsening, treat as Grade 3-4. 
Grade 
3-4 
Severe new symptoms; new/ 
worsening 
hypoxia; 
life-
threatening. 
Discontinue magrolimab therapy. 
Hospitalize. 
Pulmonary and infectious disease consults. 
1-2 mg/kg/day methylprednisolone IV or IV 
equivalent. 
Add empirical antibiotics and consider 
prophylactic antibiotics for opportunistic 
infections. 
Consider bronchoscopy, lung biopsy. 
If improving to baseline, taper corticosteroids 
over 4-6 weeks. 
If no clinical improvement after 48 hours or 
worsening, 
consider 
additional 
immunosuppression 
(e.g., infliximab, 
cyclophosphamide, 
IV 
immunoglobulin, 
mycophenolate mofetil). 
CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; CXR = chest x-ray; IV = 
intravenous. 
 
7.2.7 
Management of Thromboembolic Events 
 
Thromboembolic events including deep vein thromboses and pulmonary embolisms have been reported in some patients 
receiving Hu5F9-G4 (magrolimab), sometimes early in therapy. 
 
• 
No clear or consistent relationship between clinical and thromboembolic events and Hu5F9-G4 (magrolimab) use 
has been observed.  
• 
Close monitoring for symptoms of thromboembolic events is required.  
• 
Patients should be treated as per standard of care.  
 
7.3 
Dinutuximab (Unituxin®) AE Management and Dose Modification Guidelines 
 
For detailed information regarding management of AEs associated with dinutuximab (Unituxin®), please refer to the most 

                              
 
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current version of the dinutuximab (Unituxin®) prescribing information. 
 
The most common adverse drug reactions (≥ 25%) with dinutuximab are pain, pyrexia, thrombocytopenia, lymphopenia, 
infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, 
hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and 
hypocalcemia.  
 
7.3.1 
Discontinuation of Dinutuximab 
 
The administration of dinutuximab will be discontinued for the following adverse events that are possibly, probably or 
definitely related to dinutuximab administration:  
 
Table 8: Adverse Reactions Requiring Permanent Discontinuation of Dinutuximab 
Severity 
Adverse Reaction 
Grade 3 or 4 
Anaphylaxis 
Grade 3 or 4 
Serum sickness 
≥Grade 3 
Pain unresponsive to maximum supportive measures 
Grade 4 
Sensory neuropathy  
Grade 3 
Sensory neuropathy that interferes with daily activities for more than 2 weeks 
≥Grade 3 
Peripheral motor neuropathy  
≥Grade 3 
Decrease in vision if not improved to Grade 1 or better before next dose is due. 
Grade 4 
Hyponatremia despite appropriate fluid management 
 
7.3.2 
Dose Modification of Dinutuximab 
 
The administration of dinutuximab will be modified for the following adverse events that are possibly, probably or definitely 
related to dinutuximab administration. 
 
7.3.2.1 
Treatment of dinutuximab-induced hypotension (without evidence of allergic reaction) 
a. If hypotension is severe and accompanied by poor perfusion, end organ dysfunction, or acidemia – Pediatric 
Advanced Life Support (PALS) guidelines should be followed and dinutuximab infusion discontinued. 
b. In the absence of poor perfusion, end organ dysfunction or acidemia, moderate hypotension is defined as: 
i. Symptomatic decreases in blood pressure (BP) and/or 
ii. Systolic BP < 5th percentile based on age and height and baseline BPs OR 
iii. Systolic or diastolic BP decrease by > 20% below baseline. 
c. For patients with moderate hypotension in the absence of poor perfusion, end organ dysfunction, or 
acidemia: 
i. Immediately hold dinutuximab 
ii. Give normal saline bolus (20 mL/kg as rapidly as possible) 
iii. Stop or adjust doses of narcotics and sedating H1 blockers 
iv. Consider use of Trendelenberg position 
d. If hypotension persists after the above measures have been taken: 

                              
 
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i. Reassess perfusion and end organ function 
ii. Follow PALS algorithm if indicated 
iii. Repeat NS bolus OR 
iv. Consider use of albumin if albumin < 3 gm/dL 
v. Consider use of RBCs if Hb < 10 gm/dL 
vi. Consider use of platelets if count < 50,000/uL 
vii. Consider transfer to intensive care unit. 
e. If hypotension persists after 2 volume boluses, give an additional bolus and prepare to administer pressors 
i. Epinephrine or norepinephrine is preferred over dopamine if possible 
f. Resumption of dinutuximab 
i. For patients whose hypotension resolves promptly and completely with limited volume 
resuscitation (≤ 40 mL/kg) and without requirement for pressor support, dinutuximab may be 
restarted at 50% of the previous infusion rate. The dinutuximab may be restarted on same day if it 
is possible to do so within 20 hours of the start of the day’s infusion. If blood pressures are stable 
for 2 hours, the infusion may be given at full rate for that day and subsequent days. If the patient 
again experiences hypotension requiring multiple volume boluses (e.g., > 40 mL/kg) when 
dinutuximab is given at full rate but tolerates the 50% infusion rate, the remaining days’ doses of 
dinutuximab should be given at the 50% rate of infusion. If > 20 hours have elapsed since the start 
of the infusion, restart dinutuximab the following day.  
1. If blood pressures are stable for 2 hours after resumption of dinutuximab at the reduced 
rate, the remainder of the antibody infusion may be given at the full rate  
2. If hypotension recurs at the reduced rate, the measures above should again be taken and no 
further dinutuximab should be given that day. The antibody infusion may be restarted the 
following day after ensuring that the patient is volume replete. The antibody rate upon 
resumption of treatment should be 50% of the initial rate. If blood pressures are stable for 
2 hours, the infusion may be given at full rate for that day and subsequent days. If the 
patient’s blood pressures are only stable at the 50% rate and not at full rate, the remaining 
days’ doses of dinutuximab should be given at the 50% rate of infusion.  
ii. For patients who require multiple volume boluses for hemodynamic stabilization, dinutuximab 
should be resumed the following day at 50% of the initial infusion rate.  
1. If blood pressures are stable for 2 hours after resumption of dinutuximab at the reduced 
rate, the remainder of the antibody infusion may be given. 
2. If hypotension recurs at the reduced rate, the measures above should again be taken and no 
further dinutuximab should be given that day. The antibody infusion may be restarted the 
following day after ensuring that the patient is volume replete. The antibody rate upon 
resumption of treatment should be 50% of the initial rate. If blood pressures are stable for 
2 hours, the infusion may be given at full rate for that day and subsequent days. If the 
patient’s blood pressures are only stable at the 50% rate and not at full rate, the remaining 
days’ doses of dinutuximab should be given at the 50% rate of infusion.  
iii. For patients who require pressors for treatment of hypotension, if blood pressure is stable off 
pressors for at least 6 hours, administration of dinutuximab may be resumed at 50% of the initial 
infusion rate on the day following the hypotensive episode. Care should be taken to ensure that the 
patient is volume replete. Dinutuximab should not be given to patients who continue to require 
pressor support. Patients who require pressor support for ≥ 24 hours due to treatment-related 
hypotension despite appropriate volume resuscitation should discontinue protocol therapy. Patients 

                              
 
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who again require pressor support when dinutuximab is resumed should discontinue protocol 
therapy.  
7.3.2.2 
Treatment of Allergic Reactions/Infusion Reactions  
a. Mild allergic reactions/infusion reactions to dinutuximab infusion  
i. A mild allergic reaction is limited to rash, flushing, urticaria, mild dyspnea – Grade 1 or 2  
ii. The following recommendations do NOT apply to Grade 3 or 4 allergic reactions, including 
anaphylaxis 
iii. Management  
• 
Decrease rate of dinutuximab to 50% of full rate  
• 
Perform serial exams at bedside  
• 
Administer H1 blocker (diphenhydramine, cetirizine recommended)  
• 
Administer H2 blocker  
• 
When symptoms resolve, resume original infusion rate  
• 
If symptoms recur when original rate is resumed, decrease to 50% rate again  
• 
Infusion must be stopped after 20 hours (whether the full dose of dinutuximab has been 
administered or not); document total amount of drug given in the 20-hour time period  
b. Moderate to severe allergic reactions/infusion reactions to dinutuximab infusion  
i. Moderate to severe reactions include any of the following: symptomatic bronchospasm, allergy-
related edema/angioedema, hypotension, or anaphylaxis – Grade 3 or 4  
ii. The following recommendations do NOT apply to Grade 1 or 2 allergic reactions  
iii. Management: Immediately hold dinutuximab  
• 
Assess airway, breathing and circulation  
• 
Follow institutional guidelines for rapid response team notification if clinically indicated  
• 
For airway concerns  
o Administer oxygen and albuterol immediately for bronchospasm  
o Administer IV diphenhydramine  
o Administer epinephrine (1:1000 IM recommended) immediately if upper airway involved 
or if airway issues are accompanied by cardiovascular collapse  
o Administer IV hydrocortisone (1-2 mg/kg) if the patient has frank anaphylaxis with 
cardiorespiratory collapse OR if ≥ 2 doses of epinephrine are required OR if moderate to 
severe symptoms recur upon rechallenge with dinutuximab  
• 
For hypotension in the setting of allergic reaction  
o Give normal saline bolus (20 mL/kg as rapidly as possible)  
o Stop or adjust doses of narcotics and sedating H1 blockers  
o Consider use of Trendelenberg position  
o See previous section for management of persistent hypotension  
• 
For patients with mild bronchospasm or angioedema that does not impact breathing, completely 
resolves without the use of epinephrine and hydrocortisone and for patients whose hypotension 
resolves following volume bolus, dinutuximab may be resumed at 50% of the previous rate of 
infusion on the same day as the reaction occurred. If symptomatic angioedema or asymptomatic 
bronchospasm recurs when the dinutuximab is restarted, discontinue immunotherapy for that 
day and if symptoms/signs resolve completely that day, resume the next day with additional 

                              
 
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pre-medication of hydrocortisone 1-2 mg/kg IV. For this re-challenge, the infusion should be 
given in an ICU setting.  
o For patients whose bronchospasm or angioedema requires the use of systemic epinephrine, 
protocol therapy should be discontinued.  
o For patients with bronchospasm or angioedema that does not require systemic epinephrine 
but whose hypotension requires more extensive volume resuscitation, guidance in Section 
7.3.2.1 should be followed.  
7.3.2.3 
Management of capillary leak syndrome (≥ Grade 3)  
a. Hold dinutuximab infusion  
b. Provide oxygen, fluids as needed  
c. Diuretics should be used with caution and hypotension avoided  
d. See Section 7.3.2.1 for management of hypotension, anemia and hypoalbuminemia  
e. Do NOT resume dinutuximab therapy if symptoms of severe capillary leak syndrome persist on the same 
day or subsequent days of a given cycle. Only resume dinutuximab therapy when the capillary leak 
syndrome resolves or requires less significant intervention (Grade 2 or less).  
f. If capillary leak resolves, may resume dinutuximab infusion at 50% rate the same day and for subsequent 
doses during a given cycle. The infusion may be given at the full rate at the start of subsequent cycles  
g. If mechanical ventilation (any duration) or pressor support for ≥ 24 hours is required due to therapy-related 
capillary leak syndrome, the patient should discontinue protocol therapy. 
7.3.2.4 
Management of renal insufficiency (unrelated to hypotension)  
a. Consider the possibility of renal hypoperfusion in the context of borderline hypotension; administer volume 
if appropriate  
b. If the patient’s creatinine is elevated to ≥ 2 x the upper limit of normal for age/gender (see table in Section 
3.2.6.2) and elevation persists despite optimized fluid management, hold dinutuximab  
c. Modify dosing of concomitant medications that may contribute to or be affected by renal insufficiency  
d. When urine output returns to normal and creatinine returns to < 2 x upper limit of normal for age/gender, 
resume dinutuximab at 50% rate. If renal function normalizes by the following day, dinutuximab may be 
administered at full rate. If renal function is not sufficiently improved (urine output normal and creatinine 
< 2x ULN for age/gender) by Day 7, no further dinutuximab should be given during that cycle of therapy. 
If renal function has normalized by the planned start date for the next cycle, retreatment with dinutuximab 
is permitted  
7.3.2.5 
Management of hyponatremia (≥ Grade 3; Na < 130 mEq/L and symptomatic or 120-124 mEq/L regardless of 
symptoms)  
a. Change hypotonic fluids to isotonic fluids as compatibilities permit  
b. Avoid administration of oral free water  
c. Correct fluid losses due to diarrhea  
d. 3% saline is only indicated in the following settings:  
• 
hyponatremia leading to seizure  
• 
drop in sodium level > 10 points in 6 hours or less  
• 
sodium level < 117 mEq/L  
e. If Grade 4 hyponatremia persists despite optimal fluid management, discontinue dinutuximab for the 
remainder of the cycle. Sodium should be monitored closely during the next cycle of therapy. If 
hyponatremia improves to Grade 2 or better, or baseline, empiric dose reduction is not required at the start 
of the next cycle of therapy, though dinutuximab would again be discontinued if Grade 4 hyponatremia 
were to persist despite optimal fluid management. In such cases, patient should discontinue protocol 
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7.3.2.6 
Management of fever in the absence of hypotension  
a. Administer antipyretics  
b. Adjust fluids to account for insensible losses if fever is persistent  
c. Obtain blood culture  
d. Administer empiric antibiotics if suggested by institutional policy  
7.3.2.7 
Management of treatment-related pain 
a. No further dinutuximab therapy should be given to patients who experience treatment related Grade 3 pain 
that cannot be controlled by narcotics during a given cycle. Treatment with gabapentin or similar agent 
should be initiated if not already being administered. If pain that is not controlled with narcotics recurs 
during a subsequent cycle, the patient should discontinue protocol therapy  
b. For patients with treatment-related Grade 3 pain requiring intravenous narcotics for ≥ 48 hours following 
completion of dinutuximab therapy, gabapentin or similar agent should be initiated if not already being 
administered. If pain requiring prolonged intravenous narcotics (≥48 hours following completion of 
dinutuximab therapy) recurs during a subsequent cycle despite this intervention, the patient should 
discontinue protocol therapy.  
7.3.2.8 
Management of visual changes  
a. Dinutuximab may cause impaired accommodation and/or dilated pupils with sluggish light reflex with or 
without photophobia. No dose modifications, dose reductions, or changes in infusion rate should be made 
unless there is associated vision loss. If this occurs in conjunction with Grade 3 decrease in vision, 
dinutuximab should be discontinued. If visual loss improves to Grade 1 or better before the next 
immunotherapy course is due, the patient should receive dinutuximab at a dose that is 50% reduced 
compared to the prior dose. If the lower dose of dinutuximab is tolerated without worsening of ocular 
toxicity, full dose dinutuximab should be given in subsequent courses. If visual toxicity worsens, the patient 
should discontinue protocol therapy.  
b. Dose reductions for dilated pupils or changes in accommodation without vision loss are not required.  
7.3.2.9 
Management of serum sickness  
a. Identification of serum sickness – signs and symptoms include arthralgias/arthritis, splenomegaly, 
lymphadenopathy, glomerulonephritis in the presence of persistent fevers, cutaneous eruptions.  
b. Serum sickness typically develops 1 to 3 weeks after administration of the causative agent but can develop 
within 12-36 hours in patients who have previously been sensitized to the causative agent.  
c. Patients with ≥ Grade 3 serum sickness should discontinue protocol therapy.  
d. For Grade 2 serum sickness, antihistamines should be prescribed.  
7.3.2.10 Management of neurotoxicity  
a. Patients who develop Grade 4 neurotoxicity should discontinue protocol therapy.  
b. Dinutuximab should be discontinued for the remainder of the current cycle of therapy for patients who 
develop Grade 3 sensory neuropathy or Grade 3 motor neuropathy. If abnormalities resolve by start of next 
cycle of therapy, the patient may receive 50% dose of dinutuximab (i.e., dinutuximab dose 8.75 mg/m2). If 
symptoms do not completely resolve or recur with dinutuximab then the patient should discontinue protocol 
therapy.  
 
8 
AGENT INFORMATION 
 
A list of the adverse events and potential risks associated with the investigational or commercial agents administered in this 
study can be found in Section 10.1. 
 

                              
 
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8.1 
CTEP IND Agent(s) 
 
8.1.1 
Hu5F9-G4 (magrolimab), NSC 809249 
 
Other names: Magrolimab or 5F9 
 
Classification: A monoclonal antibody CD47 inhibitor 
 
CAS Registry Number: 1682749-68-3 
 
Molecular Formula: C6462H9960N1718O2027S48 
M.W.: 145687.6 Daltons (predicted) 
 
Mode of Action: Phagocytosis of tumor cells is blocked when CD47, a cell surface glycoprotein widely expressed by 
cancer cells, binds to the receptor, SIRPα, found on innate immune system cells like macrophages and dendritic cells. 
Hu5F9-G4 (magrolimab) blocks the binding of this ‘don’t eat me’ signal which then allows the activation of 
macrophages to phagocytose cancer cells through the induction of pro-phagocytic signaling. Nonclinical studies show 
that CD47 inhibition combined with other anti-tumor antibodies like rituximab or cetuximab has the potential to provide 
synergistic pro-phagocytic signaling to macrophages.  
 
Description: Hu5F9-G4 (magrolimab) is a recombinant humanized IgG4 monoclonal antibody of the IgG4 kappa 
isotype containing a Ser-Pro substitution in the hinge region of the heavy chain. It comprises a disulfide linked 
glycosylated tetramer, consisting of 2 identical 444 amino acid heavy gamma chains and 2 identical 219 amino acid 
kappa light chains.  
 
How Supplied: Hu5F9-G4 (magrolimab) injection is an investigational agent supplied by Gilead and distributed to 
investigators by the CTEP Division of Cancer Treatment and Diagnosis (DCTD), NCI as 200 mg/10 mL (20 
mg/mL) single-use vials in a type I borosilicate glass vial with butyl rubber stopper and aluminum seal. Hu5F9-G4 
(magrolimab) is a sterile, clear to slightly opalescent, colorless to slightly yellow, preservative-free liquid in 10 mL 
vials. The product is formulated in 0.01% (weight/volume [w/v]) polysorbate 20, 5% (w/v) sorbitol, 10 mM sodium 
acetate, pH 5.0, and sterile water for injection.  Hu5F9-G4 (magrolimab) is provided to the NCI under a 
Collaborative Agreement between the Pharmaceutical Collaborator and the DCTD, NCI (see Section Error! 
Reference source not found.). 
 
Preparation: Acceptable IV bags are: Polyvinyl chloride (PVC) preferably without DEHP or non-PVC alternatives 
such as ethylene vinyl acetate, polypropylene (ViaFlo®) or combination of ethylene and polypropylene (Excel® or 
IntraVia®). 
 
The following proprietary closed system transfer devices (CSTDs) are compatible with magrolimab: PhaSeal, PhaSea 
Optima, Equashield, ChemolockT, SmartSite with Texium and Spiros. 
 
▪ 
For doses of 1 mg/kg or less, dilute dose in 250 mL 0.9% sodium chloride 
▪ 
For doses greater than 1 mg/kg, dilute dose in 500 mL 0.9% sodium chloride. A 250 mL 0.9% sodium chloride 
may be used to prepare doses for subjects with volume restriction. Refer to the table below for the total infusion 
volumes for each age group.  
 
- 
Obtain the required number of vials from stock and examine them for discoloration, cloudiness or particles. Do not 
use if particulate matter or discoloration is noted. 
- 
Remove the equivalent Hu5F9-G4 (magrolimab) calculated dose volume from the 250 mL or 500 mL IV bag if 
using a prefilled 0.9% sodium chloride IV bag.  

                              
 
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- 
Add the calculated dose volume of Hu5F9-G4 (magrolimab) into the 0.9% sodium chloride IV bag. 
- 
Gently invert the IV bag 3-6 times to mix the solution. Avoid foaming IV solution. If particulate matter or 
discoloration occurs, do not use the IV preparation.  
 
Total Infusion Volume per Age Group 
 
Age Group 
Priming Infusion Volume (mL) – 
infused over 3 hours (+/- 30 
minutes) 
Maintenance 
Infusion 
Volume 
(mL) – infused over 2 hours (+/- 10 
minutes) 
≥1 year to < 2 years 
50 
100 
2 years to < 6 years 
250 
250 
6 years to < 12 years 
250 
250 
12 years to < 18 years 
250 
500 
Adult 
250 
500 
 
The prepared IV solution can be stored at 250 C and must be used within 8 hours of preparation. Discard the prepared 
IV solution if exceeding 8 hours. Do not refrigerate the prepared IV solution. There is no stability data to support the 
prepared IV solution stored at 2°C - 8°C (36° F to 46° F). 
 
Do not mix with any other drug in the infusion bag or administration set. 
Storage: Store vials at 2°C - 8°C (36° F to 46° F) in the original carton, protected from light. Do not freeze. 
 
If a storage temperature excursion is identified, promptly return Hu5F9-G4 (magrolimab) to 2°C -8°C (36° F to 46° 
F) and quarantine the supplies. Provide a detailed report of the excursion (including documentation of temperature 
monitoring and duration of the excursion) to PMBAfterHours@mail.nih.gov for determination of suitability. 
 
Stability:  Shelf-life stability studies of the intact or unused vials are on-going. 
 
CAUTION:  The single-use injectable vial contains no antibacterial preservatives. Therefore, it is advised that the 
reconstituted product be discarded 8 hours after initial entry.  
 
Route of Administration: Intravenous. Do not administer as an IV bolus. 
Method of Administration:  A priming dose of Hu5F9-G4 (magrolimab) is required in Cycle 1 Day 1. The priming 
dose (1 mg/kg) will be infused over 3 hours (+/- 30 minutes) via a peripheral or central line. Protecting IV bag from 
light is not required. In-line IV filter set is not required. Subsequent IV doses are to be infused over 2 hours (+/- 10 
minutes). 
 
Patient Care Implications: Advise men and women of reproductive potential to use effective contraception while 
receiving study treatment and for 4 months after the last dose of Hu-5F9. Male patients whose partners are pregnant 
may continue study treatment and should use barrier method contraception (condom) to prevent exposing the fetus. 
Refer to the protocol Section 6.8 for specific guidance. 
 
Since infusion reactions can occur, all patients should be monitored for 1-hour post-infusion for the priming dose. 
Patients who experience any treatment-related adverse events during the observation period should be further 
monitored as clinically appropriate (e.g., for up to 24 hours post-dose). All patients should be monitored for 1-hour 

                              
 
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post-infusion for Cycle 1. Further doses (Cycle 2+) do not require post-infusion observation. Patients who 
experience any treatment-related AEs during the observation period should be further monitored as clinically 
appropriate. Follow the protocol’s instructions for managing infusion symptoms and hypersensitivity to Hu5F9-G4 
(magrolimab). 
 
Availability: Hu5F9-G4 (magrolimab) is an investigational agent supplied to investigators by the Division of 
Cancer Treatment and Diagnosis (DCTD), NCI. 
 
If the study agent is provided by the NCI under a Collaborative Agreement with the agent manufacturer, the text 
below must be included in the protocol. Information on the study agent’s Collaborative Agreement status will be 
provided in the approved LOI response letter.  
 
Hu5F9-G4 (magrolimab) is provided to the NCI under a Collaborative Agreement between the Pharmaceutical 
Collaborator and the DCTD, NCI (see Section Error! Reference source not found.). 
 
8.1.2 
Dinutuximab (Chimeric Monoclonal Antibody 14.18 (UTC)), NSC 764038 
Other Names: Chimeric Monoclonal Antibody 14.18 (UTC); human/murine anti-GD2 monoclonal antibody; chimeric 
anti-GD2; chimeric mAb 14.18; ch14.18 
Classification:  Chimeric/human monoclonal antibody 
 
Description: Dinutuximab, Chimeric MOAB 14.18 (UTC) is an anti-GD2 monoclonal antibody composed of the 
variable region heavy and light chain genes of the murine mAb 14.G2a and the human constant region genes for heavy 
chain IgG1 and light chain kappa. 
 
Mode of Action: Dinutuximab exerts its antitumor effect by binding specifically to the disialoganglioside GD2, an 
antigen found in human tumors of neuroectodermal origin such as melanoma and neuroblastoma. This chimeric 
antibody has been shown to lyse melanoma and neuroblastoma cells through the process of antibody-dependent cell-
mediated cytotoxicity and complement-dependent cytotoxicity. By targeting the GD2 antigen on the cell surface, 
chimeric MOAB 14.18 may also prevent attachment of circulating malignant cells to the extracellular matrix. 
Additionally, dinutuximab mediates lysis of several melanoma and neuroblastoma cells lines in a dose dependent 
manner in the presence of potent mediators of chimeric MOAB 14.18-dependent cytotoxicity, such as human peripheral 
blood mononuclear cells and granulocytes, in particular neutrophils, especially in the presence of recombinant human 
granulocyte-macrophage colony-stimulating factor. 
 
How Supplied: Dinutuximab is manufactured by United Therapeutics and distributed by the CTEP, DCTD, NCI. 
Do not use commercial supply. Dinutuximab is provided as a sterile solution in single-dose vials containing 17.5 
mg/5 mL (3.5 mg/mL) in 20 mM Histidine, 150 mM NaCl, 0.05% Tween 20 at pH 6.8. 
Dose: 17.5 mg/m2/dose 
 
Preparation: Withdraw the required dose of chimeric dinutuximab from the vial(s) and inject the exact volume for 
the 17.5 mg/m2/day dose into a 100 mL bag of 0.9% sodium chloride. The use of a filter during preparation is not 
required. 
 
Route of Administration: Intravenous (IV) infusion. 
 
Method of Administration: The dose will be administered by IV infusion over 10-20 hours per Figure 2. 
 
Storage and Handling: Intact vials should be stored in the refrigerator (2ºC to 8ºC). 

                              
 
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Stability: Stability studies of the intact vials are ongoing. Dinutuximab is stable at room temperature for at least 24 
hours when diluted to a concentration between 0.044 mg/mL and 0.56 mg/mL; however, the final dosage form 
should be prepared immediately prior to administration as there is a maximum infusion time of 20 hours. The 
minimum infusion time for the antibody infusion is 10 hours. 
 
If a storage temperature excursion is identified, promptly return ch14.18 (dinutuximab) to the refrigerator 
temperature and quarantine the supplies.  Provide a detailed report of the excursion (including documentation of 
temperature monitoring and duration of the excursion) to PMBAfterHours@mail.nih.gov for determination of 
suitability.  
8.1.3 
Agent Ordering and Agent Accountability 
 
NCI-supplied agents may be requested by eligible participating Investigators (or their authorized designee) at each 
participating institution.  The CTEP-assigned protocol number must be used for ordering all CTEP-supplied 
investigational agents.  The eligible participating investigators at each participating institution must be registered 
with CTEP, DCTD through an annual submission of FDA Form 1572 (Statement of Investigator), NCI Biosketch, 
Agent Shipment Form, and Financial Disclosure Form (FDF).  If there are several participating investigators at one 
institution, CTEP-supplied investigational agents for the study should be ordered under the name of one lead 
participating investigator at that institution. 
 
Confirmation of patient enrollment is required for starter supply. 
 
Submit agent requests through the PMB Online Agent Order Processing (OAOP) application.  Access to OAOP 
requires the establishment of a CTEP Identity and Access Management account and the maintenance of an “active” 
account status, a “current” password, and active person registration status.  For questions about drug orders, 
transfers, returns, or accountability, call or email PMB any time.  Refer to the PMB’s website for specific policies 
and guidelines related to agent management.   
 
8.1.3.1 
Agent Inventory Records  
 
The investigator, or a responsible party designated by the investigator, must maintain a careful record of 
the receipt, dispensing and final disposition of all agents received from the PMB using the appropriate NCI 
Investigational Agent (Drug) Accountability Record (DARF) available on the CTEP forms page.  Store 
and maintain separate NCI Investigational Agent Accountability Records for each agent, strength, 
formulation and ordering investigator on this protocol. 
 
8.1.4 
Investigator Brochure Availability 
 
The current versions of the IBs for the agents will be accessible to site investigators and research staff through the 
PMB OAOP application. Access to OAOP requires the establishment of a CTEP IAM account and the maintenance 
of an “active” account status, a “current” password and active person registration status. Questions about IB access 
may be directed to the PMB IB Coordinator via email. 
 
8.1.5 
Useful Links and Contacts 
 
• 
CTEP Forms, Templates, Documents: http://ctep.cancer.gov/forms/ 
• 
NCI CTEP Registration: RCRHelpDesk@nih.gov 
• 
PMB policies and guidelines: http://ctep.cancer.gov/branches/pmb/agent_management.htm  

                              
 
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• 
PMB Online Agent Order Processing (OAOP) application:  https://ctepcore.nci.nih.gov/OAOP 
• 
CTEP Identity and Access Management account: https://ctepcore.nci.nih.gov/iam/  
• 
CTEP IAM account help: ctepreghelp@ctep.nci.nih.gov  
• 
IB Coordinator: IBCoordinator@mail.nih.gov  
• 
PMB email: PMBAfterHours@mail.nih.gov 
• 
PMB phone and hours of service: (240) 276-6575 Monday through Friday between 8:30 am and 4:30 pm (ET) 
 
9 
STATISTICAL CONSIDERATIONS 
 
9.1 
Responsibility for Analyses  
 
The statistical analysis of the data obtained from this trial will be the responsibility of Fred Hutchinson Cancer Center as 
part of the Pediatric CITN.  
 
9.2 
Study Design/Endpoints 
 
9.2.1 
Dose Finding Cohort (Arm A) Primary Endpoint 
 
The primary objective is to determine the safety and tolerability of Hu5F9-G4 (magrolimab) in combination with 
dinutuximab in children and young adults with relapsed/refractory (R/R) neuroblastoma (NBL) and osteosarcoma, and to 
determine the recommended phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) given in combination with dinutuximab. All 
patients who receive any amount of the study drug will be evaluable for toxicity. There will be two timepoints at which 
dose limiting toxicities (DLTs) will be measured to establish the maximum tolerated dose (MTD): during the ‘single agent 
Safety Lead-In’ in which patients with osteosarcoma or NBL will receive Hu5F9-G4 (magrolimab) during the first 3 weeks, 
and during Cycle 1 (21 days) of the combination of Hu5F9-G4 (magrolimab) and dinutuximab (Figure 2) as described in 
Section 6.3. If patients in the ‘single agent Safety Lead-in’ cohort or during Cycle 1 combination of Hu5F9-G4 
(magrolimab) and dinutuximab discontinue participation prior to the safety evaluation for reasons other than the occurrence 
of a DLT (e.g., withdrawal of consent, rapid tumor progression, death due to rapid tumor progression, AE that does not 
meet DLT criteria), they will not be evaluable for MTD and will be replaced in the appropriate dose-finding group (‘single 
agent Safety Lead-In’ or Cycle 1 of Arm A).  
 
If a patient is replaced to determine safety in Cycle 1 of Arm A, and the dose of Hu5F9-G4 (magrolimab) has NOT been 
deemed safe, i.e., 3 patients have not completed the Safety Lead-in without DLT, the replaced patient will undergo priming 
dose of Hu5F9-G4 (magrolimab), undergo the Safety Lead-in and then proceed to Cycle 1. This patient will be evaluable 
for DLT in the Safety Lead-in group. 
 
If 3 patients have received Hu5F9-G4 (magrolimab) during the Safety Lead-in and the dose of Hu5F9-G4 (magrolimab) has 
been deemed safe, a patient being replaced in Cycle 1 of Arm A, will undergo a priming dose of Hu5F9-G4 (magrolimab) 
and proceed directly to Cycle 1 (combination of Hu5F9-G4 (magrolimab) and dinutuximab) for determination of MTD in 
the combination cohort. 
 
Establishment of safety of the combination of Hu5F9-G4 (magrolimab) and dinutuximab will be completed in the first 3 
patients enrolled in Arm B as described in section 6.1.1.2.  
The safety and tolerability of Hu5F9-G4 (magrolimab) plus dinutuximab will be assessed by:  
• 
Suspected adverse events, and  
• 
Suspected serious adverse events  
 
As evidenced by:  
• 
Changes in clinical laboratory tests (clinical chemistry, hematology, etc).  

                              
 
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• 
Changes in vital signs (blood pressure, pulse, respiratory rate and body temperature). 
• 
Changes in physical exams. Signs and symptoms assessed may require additional testing as clinically indicated 
such as ECG, PFT, radiographic studies, etc.  
• 
Subject reported signs and symptoms  
 
Safety data will be analyzed per standard methods and interpreted descriptively. Safety data will be summarized for each 
disease group separately and for both disease groups combined. Adverse events will be assessed using the CTCAE version 
5.0 for type and severity of event. Serious Adverse Events will be summarized for each disease group and for both disease 
groups combined. Reasons for discontinuation of study therapy will be tabulated. 
 
9.2.2 
Expansion Cohorts B1-3 (Arm B) Primary Endpoint 
 
The primary objective for the expansion cohorts is to Evaluate the Overall Response Rate (ORR) of patients treated with 
Hu5F9-G4 (magrolimab) at RP2D and dinutuximab (see Figure 2) as per Section Error! Reference source not found.. The 
three expansion cohorts are defined as: 
 
Cohort B1: Patients with relapsed/refractory confirmed NBL: measurable NBL/ganglioneuroblastoma; 
Cohort B2: Patients with relapsed/refractory evaluable NBL; and 
Cohort B3: Patient with relapsed/refractory measurable osteosarcoma. 
 
Each cohort will be evaluated for response which will include a stopping rule for futility as follows: 
 
Expansion Cohort B1 
 
 
Measurable soft tissue disease will be evaluated as per the International Neuroblastoma Response Criteria (INRC) (Park et 
al., 2017), and responses will be determined as either complete response (CR), partial response (PR), stable disease (SD) or 
progressive disease (PD). Response rates will be calculated for the confirmed neuroblastoma cohort whose best response is 
a CR or PR.  Response is defined relative to baseline disease. This combination will not be considered to be of sufficient 
interest for further evaluation if the true response rate is 5% and of sufficient activity if the true response rate is 25%. If the 
combination has a true response rate of 5%, the rule described above will identify it of sufficient activity for further study 
with a probability of 0.07 (type1 error) and the trial will have an expected sample size of 14 with 60% probability of early 
termination. If the combination has a true response rate of 25%, the rule described above will identify it of sufficient activity 
for further study with probability 0.88 (power against the alternative hypothesis P = 0.25).   
 
Expansion Cohort B2 
 
Evaluable disease will be evaluated with 123I-MIBG in conjunction with anatomical imaging or bone marrow aspiration; 
 
Cumulative Number of 
Responses 
Decision 
Stage 1: Enter 10 patients 
0 
Terminate this cohort: agent ineffective  
1 or more 
Inconclusive result, continue cohort to enroll to 
stage 2 
Stage 2: Enter additional 10 
patients 
2 or less 
Terminate this cohort: agent ineffective 
3 or more 
Terminate this cohort: agent effective 

                              
 
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FDG-PET may be used for tumors that are not MIBG-avid as per the International Neuroblastoma Response Criteria 
(INRC). Overall response rate (ORR) as measured by INRC: Initially 10 eligible subjects will be treated with Hu5F9-G4 
(magrolimab) and dinutuximab at RP2D (including those in the safety evaluation); if 0 responses occur, enrollment will 
stop to this cohort. If 1 or more subjects respond, enrollment will continue to a total of 20 subjects with evaluable 
neuroblastoma treated at the RP2D. If 3 or more evaluable subjects with evaluable disease have a response, this combination 
in this cohort will be considered of sufficient interest to warrant additional study. The following Simon’s optimal two stage 
design will be used for this cohort: 
 
The response criteria for this cohort will be as defined in INRC. Responses will be determined as either complete response 
(CR), partial response (PR), stable disease (SD), minor response (MR), or progressive disease (PD). Response rates will be 
calculated for the confirmed neuroblastoma cohort whose best response is a CR or PR. Response is defined relative to 
baseline disease. This combination will not be considered to be of sufficient interest for further evaluation if the true response 
rate is 5% and of sufficient activity if the true response rate is 25%. If the combination has a true response rate of 5%, the 
rule described above will identify it of sufficient activity for further study with a probability of 0.07 (type1 error) and the 
trial will have an expected sample size of 14 with 60% probability of early termination. If the combination has a true 
response rate of 25%, the rule described above will identify it of sufficient activity for further study with probability 0.88 
(power against the alternative hypothesis P = 0.25). 
 
Expansion Cohort B3 
 
Overall response rate (ORR) as measured by RECIST v1.1: Initially 10 eligible subjects will be treated with Hu5F9-G4 
(magrolimab) and dinutuximab at RP2D; if 0 responses (PR or CR) occur, enrollment will stop to this cohort.  If 1 or more 
subjects respond, enrollment will continue to a total of 20 subjects with measurable osteosarcoma treated at the RP2D. If 3 
or more evaluable subjects with measurable disease have a response, this combination in this cohort will be considered of 
sufficient interest to warrant additional study. The following Simon’s optimal two stage design will be used for this cohort: 
 
 
Measurable soft tissue disease will be evaluated using either CT or MRI, and lesions will be measured according to RECIST 
 
Cumulative Number of 
Responses 
Decision 
Stage 1: Enter 10 patients 
0 
Terminate this cohort: agent ineffective  
1 or more 
Inconclusive result, continue cohort to enroll to stage 2 
Stage 2: Enter additional 10 
patients 
2 or less 
Terminate this cohort: agent ineffective 
3 or more 
Terminate this cohort: agent effective 
 
Cumulative Number of Responses 
Decision 
Stage 1: 
Enter 10 
patients 
0 
Terminate this cohort: agent ineffective  
1 or more 
Inconclusive result, continue cohort to enroll to stage 2 
Stage 2: 
Enter 
additional 
10 patients 
2 or less 
Terminate this cohort: agent ineffective 
3 or more 
Terminate this cohort: agent effective 

                              
 
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v1.1., and responses will be determined as either complete response (CR), partial response (PR), stable disease (SD) or 
progressive disease (PD). Response rates will be calculated for the osteosarcoma cohort whose best response is a CR or PR. 
Response is defined relative to baseline disease. This combination will not be considered to be of sufficient interest for 
further evaluation if the true response rate is 5% and of sufficient activity if the true response rate is 25%. If the combination 
has a true response rate of 5%, the rule described above will identify it of sufficient activity for further study with a 
probability of 0.07 (type1 error) and the trial will have an expected sample size of 14 with 60% probability of early 
termination. If the combination has a true response rate of 25%, the rule described above will identify it of sufficient activity 
for further study with probability 0.88 (power against the alternative hypothesis P = 0.25).   
 
9.2.3 
Expansion Cohort B4 Primary Endpoint 
 
The primary objective for the expansion cohort B4 is to determine the safety and feasibility of administering Hu5F9-G4 
(magrolimab) in combination with dinutuximab to patients that undergo recent resection of metastatic osteosarcoma within 
three weeks of surgery. 
 
Ten (10) evaluable subjects will be treated with Hu5F9-G4 (magrolimab) and dinutuximab at RP2D. If 3 or more subjects 
out of the 10 subjects experience complications, the lower bound of the 95% Clopper-Pearson confidence interval on the 
proportion of complications will be higher than 5%. Thus, if 3 or more subjects out of the 10 subjects experienced 
complications, the use of Hu5F9-G4 (magrolimab) in combination with dinutuximab after surgery would be considered not 
feasible. 
 
9.3 
Sample Size/Accrual Rate 
 
9.3.1 
Proposed Sample Size 
 
A minimum of 4 patients and a maximum of 82 patients will be enrolled on this trial. 
 
9.3.2 
Accrual Rate 
 
The expected accrual is 2-3 patients per month (slower during dose escalation, more rapid during expansion cohorts). We 
estimate that accrual will be completed within about 36 months.  
 
9.3.3 
Sample Size Justification 
 
A minimum of 4 patients will be enrolled on this trial if two patients at Dose Level 1 have DLTs and 2 patients at Dose 
Level -1 have DLTs. 
 
A maximum of 82 patients will be enrolled on this trial: 
• 
Six patients/dose level at Dose Level 1 and Dose Level -1 = 12 
• 
Three expansion cohorts (B1, B2 and B3) of 20 patients in each cohort  
• 
Ten patients in cohort B4. 
 
9.4 
Demographics 
 
This trial is open to all participants regardless of gender or ethnicity. Efforts will be made to extend the accrual to a 
representative population; however, in a Phase1 trial, which will accrue a limited number of patients, a balance must be 
struck between patient safety considerations and limitations on the number of individuals exposed to potentially toxic or 
ineffective treatments on the one hand and the need to explore gender, racial, and ethnic aspects of clinical research on the 

                              
 
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other. If differences in outcome that correlate to gender, racial or ethnic identity are noted, accrual may be expanded, and/or 
additional studies may be performed to investigate those differences more fully.  
 
PLANNED ENROLLMENT REPORT 
Racial Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
 
Female 
Male 
Female 
Male 
 
American Indian/  
Alaska Native 
0 
0 
0 
0 
0 
Asian 
3 
4 
0 
0 
7 
Native 
Hawaiian 
or 
Other Pacific Islander 
1 
2 
0 
0 
3 
Black 
or 
African 
American 
5 
6 
0 
0 
11 
White 
15 
22 
7 
9 
53 
More Than One Race 
2 
3 
1 
2 
8 
Total 
26 
37 
8 
11 
82 
PHS 398 / PHS 2590 (Rev. 08/12 Approved Through 8/31/2015)  
OMB No. 0925-0001/0002 
 
9.5 
Analysis of Secondary Endpoints 
 
9.5.1 
Determine the pharmacokinetics (PK) of Hu5F9-G4 (magrolimab) in children and young adults. 
 
The endpoint for PK analysis is to assess the drug concentrations achieved during this first in child trial. Samples will be 
collected in the Safety Lead-In cohort and the first 3 patients on any expansion cohorts on the following schedule: 
• 
Safety Lead-In: Day 1, Day 8, Day 15  
• 
Cycle 1: Day 1, Day 8, Day 15   
• 
Cycle 2, 3, 5, 7, 9, 11: Day 1 
• 
End of Therapy 
 
These samples will be a mandatory in the Safety Lead-In cohort and in the first three patients on any expansion cohorts (B1, 
B2, B3 and B4).  
 
The PK Analysis Set will be used for summaries of PK concentration of magrolimab versus time. Serum concentrations 
will be listed and summarized for magrolimab using descriptive statistics by sampling timepoint and cohort. Graphical plots 
of individual serum concentration versus time and mean concentration versus time by cohort will be generated. 
The samples will be tested and analyzed by PPD.  

                              
 
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9.5.2 
Observe and record anti-tumor activity 
 
Although the clinical benefit of this combination of drugs has not yet been established, the intent of offering this treatment 
is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom 
relief in addition to safety and tolerability. 
 
All eligible patients will be considered evaluable for response if they receive any doses of the combination regimen. 
Antitumor activity will be evaluated in patients with osteosarcoma according to Section 12.1 and in patients with 
neuroblastoma according to Section 12.2. 
 
9.5.3 
Evaluate the Event Free Survival (EFS) in two cohorts of osteosarcoma patients who are treated at the RP2D 
(measurable relapsed osteosarcoma and patients with pulmonary relapse undergoing resection) and compare to 
historical controls (Lagmay et al., 2016).  
 
In this trial EFS is defined as the time from the first dose of Hu5F9-G4 (magrolimab) until the earliest of: death, local 
recurrence, new metastatic disease, progression of metastatic disease or secondary malignancy, or date of last contact. The 
historical control report of EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 
6% to 19%). This study will compare the EFS of patients in the expansion cohort 3 (measurable osteosarcoma) to these 
historical controls. 
 
10 
ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS  
 
AE monitoring and reporting is a routine part of every clinical trial. The following list of AEs (Section 10.1) and the 
characteristics of an observed AE (Sections 10.2 and 10.3) will determine whether the event requires expedited reporting 
via the CTEP Adverse Event Reporting System (CTEP-AERS) in addition to routine reporting. 
 
10.1 
Comprehensive Adverse Events and Potential Risks List(s) (CAEPRs) 
 
The Comprehensive Adverse Events and Potential Risks list (CAEPR) provides a single list of reported and/or potential 
adverse events (AE) associated with an agent using a uniform presentation of events by body system. In addition to the 
comprehensive list, a subset, the Specific Protocol Exceptions to Expedited Reporting (SPEER), appears in a separate 
column and is identified with bold and italicized text. This subset of AEs (SPEER) is a list of events that are protocol specific 
exceptions to expedited reporting to NCI (except as noted below).  Refer to the 'CTEP, NCI Guidelines: Adverse Event 
Reporting Requirements' http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguidelines.pdf for 
further clarification. 
 
 
NOTE: Report AEs on the SPEER ONLY IF they exceed the grade noted in parentheses next to the AE in the SPEER.  If 
this CAEPR is part of a combination protocol using multiple investigational agents and has an AE listed on different 
SPEERs, use the lower of the grades to determine if expedited reporting is required. 
 
 
 
 
 
 
 
 

                              
 
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10.1.1 CAEPRs for CTEP IND Agent(s) 
 
10.1.1.1 CAEPRs for Hu5F9-G4 (magrolimab), NSC 809249 
 
Below is the CAEPR for Hu5F9-G4 (magrolimab). Frequency is based on 1328 patients. 
 
Version 2.2, December 6, 20231 
 
 Adverse Events with Possible  
 Relationship to Hu5F9-G4 (Magrolimab) 
 (CTCAE 5.0 Term) 
[n= 1328] 
 
 
 Specific Protocol Exceptions to 
Expedited Reporting (SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
  
Anemia 
 
 
 Anemia (Gr 2) 
 
 
Blood and lymphatic system 
disorders - Other (red blood cell 
agglutination) 
  
 
Febrile neutropenia 
 
 Febrile neutropenia (Gr 2) 
 
 
Hemolysis 
  
GASTROINTESTINAL DISORDERS 
  
 
Abdominal pain 
 
 Abdominal pain (Gr 2) 
 
Diarrhea 
 
 Diarrhea (Gr 2) 
 
Nausea 
 
 Nausea (Gr 2) 
 
Vomiting 
 
 Vomiting (Gr 2) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
 
Chills 
 
 Chills (Gr 2) 
Fatigue 
 
 
 Fatigue (Gr 2) 
 
Fever 
 
 Fever (Gr 2) 
 
Generalized edema 
 
  
INFECTIONS AND INFESTATIONS 
  
 
Lung infection 
 
  
 
 
Sepsis 
  
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 
  
Infusion related reaction 
 
 
 Infusion related reaction (Gr 2) 
INVESTIGATIONS 
  
 
Blood bilirubin increased 
 
 Blood bilirubin increased (Gr 2) 
 
Lymphocyte count decreased 
 
 Lymphocyte count decreased (Gr 2) 
 
Neutrophil count decreased 
 
 Neutrophil count decreased (Gr 2) 
 
Platelet count decreased 
 
 Platelet count decreased (Gr 2) 
 
White blood cell decreased 
 
 White blood cell decreased (Gr 2) 
METABOLISM AND NUTRITION DISORDERS 
  
 
Anorexia 
 
 Anorexia (Gr 2) 
 
Hypokalemia 
 
 Hypokalemia (Gr 2) 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
  
 
Arthralgia 
 
  
 
Back pain 
 
  
NERVOUS SYSTEM DISORDERS 
  
 
Dizziness 
 
  
 
Headache 
 
 Headache (Gr 2) 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  

                              
 
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 Adverse Events with Possible  
 Relationship to Hu5F9-G4 (Magrolimab) 
 (CTCAE 5.0 Term) 
[n= 1328] 
 
 
 Specific Protocol Exceptions to 
Expedited Reporting (SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
 
Cough 
 
  
 
Dyspnea 
 
  
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
Pruritus 
 
  
VASCULAR DISORDERS 
  
Hypotension 
 
 
  
 
 
1This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all Principal Investigators at 
the time of revision.  The current version can be obtained by contacting PIO@CTEP.NCI.NIH.GOV.  Your name, the name of the 
investigator, the protocol and the agent should be included in the e-mail. 
 
Adverse events reported on Hu5F9-G4 (Magrolimab) trials, but for which there is insufficient evidence to suggest that there 
was a reasonable possibility that Hu5F9-G4 (Magrolimab) caused the adverse event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Thrombotic thrombocytopenic purpura 
GASTROINTESTINAL DISORDERS - Colitis; Constipation; Mucositis oral; Small intestinal obstruction 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Pain 
IMMUNE SYSTEM DISORDERS - Serum sickness 
INFECTIONS AND INFESTATIONS - Conjunctivitis; Urinary tract infection 
INVESTIGATIONS - Alkaline phosphatase increased; Aspartate aminotransferase increased 
METABOLISM AND NUTRITION DISORDERS - Hypomagnesemia; Hypophosphatemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Pain in extremity 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - Tumor pain 
NERVOUS SYSTEM DISORDERS - Edema cerebral; Intracranial hemorrhage; Nervous system disorders - Other (cerebral 
hemorrhage) 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Epistaxis; Hypoxia; Pneumonitis 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Dry skin; Rash acneiform; Rash maculo-papular 
VASCULAR DISORDERS - Hypertension; Thromboembolic event 
 
 
Note: Hu5F9-G4 (Magrolimab) in combination with other agents could cause an exacerbation of any adverse event currently known to 
be caused by the other agent, or the combination may result in events never previously associated with either agent. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                              
 
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10.1.1.2 CAEPR for Dinutuximab (MoAb 14.18 chimeric (CH14.18)), NSC 764038 
 
Below is the CAEPR for Dinutuximab (MoAb 14.18 chimeric (CH14.18)). Frequency is based on 359 patients. 
 
Version 2.9, January 10, 20191 
 Adverse Events with Possible  
 Relationship to MoAb 14.18, chimeric (CH14.18) 
 (CTCAE 5.0 Term) 
 [n= 359] 
 
 
 Specific Protocol Exceptions to 
Expedited Reporting (SPEER)  
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
  
 
Anemia 
 
 Anemia (Gr 3) 
 
Disseminated intravascular 
coagulation 
 
 Disseminated intravascular 
coagulation (Gr 2) 
 
 
Hemolytic uremic syndrome2 
  
CARDIAC DISORDERS 
  
 
 
Cardiac arrest 
  
 
 
Sinus bradycardia 
  
 
Sinus tachycardia 
 
 Sinus tachycardia (Gr 3) 
EYE DISORDERS 
  
 
 
Eye disorders - Other (eye 
disorders)3 
  
GASTROINTESTINAL DISORDERS 
  
 
Abdominal pain 
 
 Abdominal pain (Gr 3) 
 
Diarrhea 
 
 Diarrhea (Gr 3) 
 
Nausea 
 
 Nausea (Gr 2) 
 
Vomiting 
 
 Vomiting (Gr 3) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
 
Edema limbs 
 
 Edema limbs (Gr 2) 
Fever 
 
 
 Fever (Gr 3) 
 
Generalized edema 
 
  
Pain 
 
 
 Pain (Gr 3) 
 
 
Sudden death NOS 
  
IMMUNE SYSTEM DISORDERS 
  
 
Allergic reaction 
 
 Allergic reaction (Gr 3) 
 
 
Anaphylaxis 
  
 
Serum sickness 
 
  
INFECTIONS AND INFESTATIONS 
  
 
 Infection4 
 
 Infection4 (Gr 3) 
 
 
Myelitis5 
  
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 
  
 
 
Infusion related reaction 
  
INVESTIGATIONS 
  
 
Alanine aminotransferase 
increased 
 
 Alanine aminotransferase increased 
(Gr 3) 
 
Aspartate aminotransferase 
increased 
 
 Aspartate aminotransferase increased 
(Gr 3) 
 
Creatinine increased 
 
 Creatinine increased (Gr 2) 
Investigations - Other 
(elevated c-reactive proteins) 
 
 
 Investigations - Other (elevated c-
reactive proteins) (Gr 2) 
 
Lymphocyte count decreased 
 
 Lymphocyte count decreased (Gr 4) 

                              
 
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 Adverse Events with Possible  
 Relationship to MoAb 14.18, chimeric (CH14.18) 
 (CTCAE 5.0 Term) 
 [n= 359] 
 
 
 Specific Protocol Exceptions to 
Expedited Reporting (SPEER)  
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
 
 
Neutrophil count decreased 
 
 Neutrophil count decreased (Gr 3) 
 
Platelet count decreased 
 
 Platelet count decreased (Gr 4) 
 
White blood cell decreased 
 
  
METABOLISM AND NUTRITION DISORDERS 
  
 
Anorexia 
 
 Anorexia (Gr 3) 
 
 Hyperkalemia 
 
 Hyperkalemia (Gr 2) 
 
 Hypoalbuminemia 
 
 Hypoalbuminemia (Gr 3) 
 
 Hypocalcemia 
 
  
 
 Hypokalemia 
 
 Hypokalemia (Gr 4) 
 
 Hyponatremia 
 
 Hyponatremia (Gr 3) 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
  
 
Back pain 
 
 Back pain (Gr 3) 
 
Pain in extremity 
 
  
NERVOUS SYSTEM DISORDERS 
  
 
Neuralgia 
 
 Neuralgia (Gr 2) 
 
 
Peripheral motor neuropathy 
  
 
Peripheral sensory neuropathy6  
 Peripheral sensory neuropathy6 (Gr 3) 
 
 
Reversible posterior 
leukoencephalopathy 
syndrome 
  
RENAL AND URINARY DISORDERS 
  
 
Proteinuria 
 
 Proteinuria (Gr 2) 
 
 
Renal and urinary disorders - 
Other (atonic urinary bladder)6 
  
 
Urinary retention6 
 
  
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  
 
Bronchial obstruction 
 
  
Cough 
 
 
 Cough (Gr 3) 
 
Dyspnea 
 
 Dyspnea (Gr 3) 
 
Hypoxia 
 
 Hypoxia (Gr 3) 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
Pruritus 
 
 Pruritus (Gr 2) 
Rash maculo-papular 
 
 
 Rash maculo-papular (Gr 2) 
 
Urticaria 
 
 Urticaria (Gr 3) 
VASCULAR DISORDERS 
  
 
Capillary leak syndrome 
 
 Capillary leak syndrome (Gr 3) 
 
Hypertension 
 
  
 
Hypotension 
 
 Hypotension (Gr 3) 
 
1This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all Principal Investigators at 
the time of revision.  The current version can be obtained by contacting PIO@CTEP.NCI.NIH.GOV.  Your name, the name of the 
investigator, the protocol and the agent should be included in the e-mail.  
 
2There have been rare instances of atypical hemolytic uremic syndrome in the absence of documented infection and resulting in renal 
insufficiency, electrolyte abnormalities, anemia, and hypertension. 
 
3Neurological disorders of the eye including blurred vision, diplopia, cycloplegia, mydriasis, photophobia, optic nerve disorder, eyelid 

                              
 
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ptosis, and fixed pupils have been observed.  
 
4Infection includes all 75 sites of infection under the INFECTIONS AND INFESTATIONS SOC. 
 
5Myelitis expressed as transverse myelitis has occurred in patients treated with chimeric MoAb 14.18. Symptoms may include 
weakness, paresthesia, sensory loss, or incontinence. 
 
6Acute urinary retention occurs during therapy and is thought to be due to fluid shifts and narcotic administration that accompany 
ch14.18 administration.  Atonic urinary bladder results in chronic urinary retention (CUR) that requires intermittent urethral 
catheterization days to weeks following chimeric MoAb 14.18 administration.  
 
Adverse events reported on MoAb 14.18, chimeric (CH14.18) trials, but for which there is insufficient evidence to suggest that 
there was a reasonable possibility that MoAb 14.18, chimeric (CH14.18) caused the adverse event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Blood and lymphatic system disorders - Other (thrombotic 
microangiopathy [e.g., thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS]); Bone marrow 
hypocellular; Febrile neutropenia; Hemolysis 
CARDIAC DISORDERS - Cardiac disorders - Other (gallop on exam); Cardiac disorders - Other (N-terminal BNP); Chest pain - 
cardiac; Heart failure; Left ventricular systolic dysfunction; Mobitz (type) II atrioventricular block; Myocardial infarction; 
Palpitations; Pericardial effusion; Supraventricular tachycardia; Ventricular tachycardia 
EAR AND LABYRINTH DISORDERS - Ear pain; Hearing impaired 
ENDOCRINE DISORDERS - Endocrine disorders - Other (transient hypoaldosteronism); Hyperthyroidism; Hypothyroidism 
EYE DISORDERS - Papilledema; Periorbital edema; Scleral disorder 
GASTROINTESTINAL DISORDERS - Abdominal distension; Ascites; Cheilitis; Colitis; Constipation; Duodenal obstruction; 
Dysphagia; Enterocolitis; Esophageal stenosis; Esophageal ulcer; Esophagitis; Gastrointestinal disorders - Other (bleeding, NOS); 
Gastrointestinal disorders - Other (esophageal stricture); Gastrointestinal disorders - Other (ischemic bowel); Gastrointestinal 
disorders - Other (pneumatosis intestinalis); Gastroparesis; Hemorrhoidal hemorrhage; Ileus; Intra-abdominal hemorrhage; Lower 
gastrointestinal hemorrhage; Mucositis oral; Oral pain; Rectal hemorrhage; Stomach pain; Typhlitis 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Chills; Death NOS; Edema face; Edema trunk; 
Fatigue; General disorders and administration site conditions - Other (cold and clammy); General disorders and administration site 
conditions - Other (vascular leak syndrome); Hypothermia; Injection site reaction; Localized edema; Non-cardiac chest pain 
HEPATOBILIARY DISORDERS - Hepatobiliary disorders - Other (cholestasis) 
IMMUNE SYSTEM DISORDERS - Cytokine release syndrome 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Fracture 
INVESTIGATIONS - Activated partial thromboplastin time prolonged; Alkaline phosphatase increased; Blood bilirubin increased; 
Cardiac troponin I increased; Cholesterol high; Ejection fraction decreased; Electrocardiogram QT corrected interval prolonged; 
Fibrinogen decreased; GGT increased; INR increased; Lipase increased; Lymphocyte count increased; Urine output decreased; 
Weight gain; Weight loss 
METABOLISM AND NUTRITION DISORDERS - Acidosis; Dehydration; Hypercalcemia; Hyperglycemia; Hypermagnesemia; 
Hypernatremia; Hypertriglyceridemia; Hypoglycemia; Hypomagnesemia; Hypophosphatemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthralgia; Arthritis; Bone pain; Chest wall pain; Muscle 
weakness lower limb; Myalgia; Neck pain 
NERVOUS SYSTEM DISORDERS - Cognitive disturbance; Depressed level of consciousness; Dysesthesia; Dysgeusia; Dysphasia; 
Encephalopathy; Extrapyramidal disorder; Headache; Hydrocephalus; Meningismus; Movements involuntary; Nystagmus; 
Oculomotor nerve disorder; Paresthesia; Seizure; Somnolence; Syncope; Tremor 
PSYCHIATRIC DISORDERS - Agitation; Anxiety; Confusion; Delirium; Hallucinations; Insomnia; Irritability; Personality change; 
Restlessness 
RENAL AND URINARY DISORDERS - Acute kidney injury; Chronic kidney disease; Glucosuria; Hematuria; Renal and urinary 
disorders - Other (acute renal insufficiency); Renal and urinary disorders - Other (urethritis); Renal hemorrhage 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Hematosalpinx; Ovarian hemorrhage; Pelvic pain; Penile pain; 
Prostatic hemorrhage; Spermatic cord hemorrhage; Testicular hemorrhage; Uterine hemorrhage; Vaginal hemorrhage 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Adult respiratory distress syndrome; Apnea; Atelectasis; 
Bronchospasm; Laryngeal edema; Laryngopharyngeal dysesthesia; Laryngospasm; Pharyngolaryngeal pain; Pleural effusion; Pleuritic 
pain; Pneumonitis; Pulmonary edema; Respiratory failure; Respiratory, thoracic and mediastinal disorders - Other (tachypnea); 

                              
 
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Stridor; Wheezing 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Dry skin; Erythema multiforme; Hyperhidrosis 
VASCULAR DISORDERS - Flushing 
 
Note: Dinutuximab (MoAb 14.18, chimeric) in combination with other agents could cause an exacerbation of any adverse event 
currently known to be caused by the other agent, or the combination may result in events never previously associated with either 
agent. 
 
Magrolimab activates macrophages as does dinutuximab. Given that dinutuximab causes pain due to GD2 expression on normal nerve 
cells, there is a theoretical potential for worsening of this pain or other neurologic toxicity such as motor dysfunction or permanent 
damage to peripheral nerve cells. 
 
 
10.2 
Adverse Event Characteristics  
 
• 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting.  All 
appropriate treatment areas should have access to a copy of the CTCAE version 5.0.  A copy of the CTCAE version 
5.0 
can 
be 
downloaded 
from 
the 
CTEP 
website 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
• 
For expedited reporting purposes only:   
- 
AEs for the agent that are bold and italicized in the CAEPR (i.e., those listed in the SPEER column, Section 
10.1) should be reported through CTEP-AERS only if the grade is above the grade provided in the SPEER. 
- 
Other AEs for the protocol that do not require expedited reporting are outlined in Section 10.3.4, if any exist. 
 
• 
Attribution of the AE: 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
10.3 
Expedited Adverse Event Reporting 
 
10.3.1 Rave-CTEP-AERS Integration 
 
The Cancer Therapy Evaluation Program Adverse Event Reporting System (CTEP-AERS) integration enables 
evaluation of post-baseline AEs entered in Rave to determine whether they require expedited reporting and 
facilitates entry in CTEP-AERS for those AEs requiring expedited reporting.    
 
All AEs that occur after baseline are collected in Medidata Rave using the Adverse Event form, which is available 
for entry at each treatment or reporting period and used to collect AEs that start during the period or persist from 
the previous reporting period.  The Clinical Research Associate (CRA) will enter AEs that occur prior to the start 
of treatment on a baseline form that is not included in the Rave-CTEP-AERS integration.  AEs that occur prior to 
enrollment must begin and end on the baseline Adverse Event form and should not be included on the standard 
Adverse Events form that is available at treatment unless there has been an increase in grade. 
 
Prior to sending AEs through the rules evaluation process, site staff should verify the following on the Adverse 
Event form in Rave: 

                              
 
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• 
The reporting period (course/cycle) is correct, and 
• 
AEs are recorded and complete (no missing fields) and the form is query-free (fields added to the form 
during study build do not need to be query-free for the integration call with CTEP-AERS to be a success). 
 
The CRA reports AEs in Rave at the time the Investigator learns of the event.  If the CRA modifies an AE, it must 
be re-submitted for rules evaluation. 
 
Upon completion of AE entry in Medidata Rave, the CRA submits the AE for rules evaluation by completing the 
Expedited Reporting Evaluation form.  Both NCI and protocol-specific reporting rules evaluate the AEs submitted 
for expedited reporting.  A report is initiated in CTEP-AERS using information entered in Medidata Rave for AEs 
that meet reporting requirements.  The CRA completes the report by accessing CTEP-AERS via a direct link on the 
Medidata Rave Expedited Reporting Evaluation form. 
 
In the rare occurrence that Internet connectivity is lost, a 24-hour notification is to be made to CTEP by telephone 
at 301-897-7497.  Once Internet connectivity is restored, the 24-hour notification that was phoned in must be entered 
immediately into CTEP-AERS using the deep link from Medidata Rave. 
Additional information about the CTEP-AERS integration is available on the CTSU website: 
 
• 
Study specific documents:  Protocols > Documents > Education and Promotion, and   
• 
Expedited Safety Reporting Rules Evaluation user guide:  Resources > CTSU Operations Information > 
User Guides. 
 
NCI requirements for SAE reporting are available on the CTEP website:  
 
• 
NCI Guidelines for Investigators:  Adverse Event Reporting Requirements is available at 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguidelines.pdf. 
 
10.3.2 Distribution of Adverse Event Reports 
 
CTEP-AERS is programmed for automatic electronic distribution of reports to the following individuals:  Principal 
Investigator and Adverse Event Coordinator(s) (if applicable) of the Corresponding Organization or Lead Organization, the 
local treating physician, and the Reporter and Submitter. CTEP-AERS provides a copy feature for other e-mail recipients.  
 
10.3.3 Expedited Reporting Guidelines 
 
Use the NCI protocol number and the protocol-specific patient ID assigned during trial registration on all reports. 
 
Note:  A death on study requires both routine and expedited reporting, regardless of causality.  Attribution to 
treatment or other cause must be provided. 
 
Death due to progressive disease should be reported as Grade 5 “Disease progression” in the system organ class (SOC) 
“General disorders and administration site conditions.”  Evidence that the death was a manifestation of underlying disease 
(e.g., radiological changes suggesting tumor growth or progression: clinical deterioration associated with a disease process) 
should be submitted.  
 

                              
 
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Phase 1 and Early Phase 2 Studies:  Expedited Reporting Requirements for Adverse Events that Occur on Studies 
under an IND/IDE within 30 Days of the Last Administration of the Investigational Agent/Intervention 1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or not they are 
considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization may be 
considered serious when, based upon 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. (FDA, 21 CFR 312.32; ICH 
E2A and ICH E6). 
 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via electronic 
submission within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 and Grade 2 Timeframes 
Grade 3-5 
Timeframes 
Resulting in 
Hospitalization  
≥ 24 hrs 
10 Calendar Days 
24-Hour 5 Calendar Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
NOTE:  Protocol specific exceptions to expedited reporting of serious adverse events are found in the Specific Protocol 
Exceptions to Expedited Reporting (SPEER) portion of the CAEPR. 
Expedited AE reporting timelines are defined as: 
o 
“24-Hour; 5 Calendar Days” - The AE must initially be submitted electronically within 24 hours of learning of the 
AE, followed by a complete expedited report within 5 calendar days of the initial 24-hour report. 
o 
“10 Calendar Days” - A complete expedited report on the AE must be submitted electronically within 10 calendar 
days of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational agent/intervention and have 
an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• 
All Grade 3, 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• 
Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 
2For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, rounded UP to the 
nearest whole day, after the agent/intervention was last administered.  Footnote “1” above applies after this reporting period. 
Effective Date:  May 5, 2011 
 
10.4 
Routine Adverse Event Reporting 
 
All Adverse Events must be reported in routine study data submissions.  AEs reported expeditiously through CTEP-
AERS must also be reported in routine study data submissions. 
 
Adverse event data collection and reporting, which are required as part of every clinical trial, are done to ensure the safety 
of patients enrolled in the studies as well as those who will enroll in future studies using similar agents. AEs are reported in 

                              
 
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a routine manner at scheduled times during the trial using Medidata Rave. For this trial the Adverse Event CRF is used for 
routine AE reporting in Rave. 
 
10.5 
Pregnancy 
 
Although not an adverse event in and of itself, pregnancy as well as its outcome must be documented via CTEP-AERS.  In 
addition, the Pregnancy Information Form included within the NCI Guidelines for Adverse Event Reporting Requirements 
must be completed and submitted to CTEP.  Any pregnancy occurring in a patient or patient’s partner from the time of 
consent to 90 days after the last dose of study drug must be reported and then followed for outcome. Newborn infants should 
be followed until 30 days old.  Please see the “NCI Guidelines for Investigators: Adverse Event Reporting Requirements 
for DCTD (CTEP and CIP) and DCP INDs and IDEs” (at http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm) 
for more details on how to report pregnancy and its outcome to CTEP.  
 
10.6 
Secondary Malignancy 
 
A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., treatment with investigational 
agent/intervention, radiation or chemotherapy). A secondary malignancy is not considered a metastasis of the initial 
neoplasm. 
CTEP requires all secondary malignancies that occur following treatment with an agent under an NCI IND/IDE be reported 
expeditiously via CTEP-AERS.  Three options are available to describe the event:  
 
• 
Leukemia secondary to oncology chemotherapy (e.g., acute myelocytic leukemia [AML])  
• 
Myelodysplastic syndrome (MDS)  
• 
Treatment-related secondary malignancy  
 
Any malignancy possibly related to cancer treatment (including AML/MDS) should also be reported via the routine 
reporting mechanisms outlined in each protocol.  
 
 
10.7 
Second Malignancy 
 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is NOT a metastasis from the initial 
malignancy).  Second malignancies require ONLY routine AE reporting unless otherwise specified. 
 

                              
 
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11 
STUDY CALENDAR 
 
Baseline/screening evaluations are to be conducted within 4 weeks (28 days) prior to start of protocol therapy. Scans must be done <4 weeks (28 days) prior 
to the start of protocol therapy. In the event that the patient’s condition is deteriorating, laboratory evaluations should be repeated within 48 hours prior to 
initiation of the next cycle of therapy. 
 
DOSE FINDING (ARM A): Priming, Safety Lead-In and Treatment Cycles1 
Treatment Cycles/Visits 
Screening 
Treatment 
Follow Up 
Week 1  
Safety Lead-In  
Cycle 1 
Cycle 2 and subsequent cycles     
End of 
Therapy 
Safety 
Follow Up17 
Priming 
Week 2-3 
Week 1 
Weeks 2-3 
Week 1 
Weeks 2-320 
Scheduling Window 
Within 28 
days 
Day 1 
Day 1 
±1 day 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Within 10 
days after 
last IP dose 
30 days after 
last IP dose 
±7 days 
Month 2, 4, 6, 
9, 12 and 
annually 
(Year 2-5) 
Administrative Procedures 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility evaluation 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Treatment 
Hu5F9-G4 (magrolimab) 
administration4 
 
X 
X 
X 
 
X 
X 
 
X4 
 
 
 
Dinutuximab 
administration5 
 
 
 
 
X 
 
 
X 
 
 
 
 
Clinical Assessments 
Height, weight6 
X 
X 
 
X 
 
 
X 
 
 
X 
X 
 
Physical exam7 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
Vital signs8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECG  
X 
 
 
 
 
 
 
 
 
 
 
 
ECHO, MUGA or Cardiac 
MRI 
X 
 
 
 
 
 
 
 
 
 
 
 
Performance status9 
X 
X 
 
X 
 
 
X 
 
 
 
X 
 
Disease evaluation10 
X 
 
 
End of Cycle 2 and 4, and then after every 4 cycles 
 
 
X 
Confirmatory imaging11 
 
As per Section Error! Reference source not found. 

                              
 
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DOSE FINDING (ARM A): Priming, Safety Lead-In and Treatment Cycles1 
Treatment Cycles/Visits 
Screening 
Treatment 
Follow Up 
Week 1  
Safety Lead-In  
Cycle 1 
Cycle 2 and subsequent cycles     
End of 
Therapy 
Safety 
Follow Up17 
Priming 
Week 2-3 
Week 1 
Weeks 2-3 
Week 1 
Weeks 2-320 
Scheduling Window 
Within 28 
days 
Day 1 
Day 1 
±1 day 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Within 10 
days after 
last IP dose 
30 days after 
last IP dose 
±7 days 
Month 2, 4, 6, 
9, 12 and 
annually 
(Year 2-5) 
Bone marrow aspiration 
and biopsy if NBL/ 
ganglioneuroblastoma10, 21 
X  ------------→ 
 
End of Cycle 2 and 4, and then after every 4 cycles 
 
 
X 
AE and SAE evaluation12 
 
Continuously 
Clinical Laboratory Tests13 
Pregnancy test14 
X 
As required locally 
CBC with differential and 
platelets 
X 
X22 
X22 
X 
 
 
X 
 
 
 
X 
 
Electrolytes, creatinine, 
urea (BUN), Ca2+, PO43-, 
Mg2+ 
X 
X 
X 
X 
 
 
X 
 
 
 
X 
 
ALT, AST, bilirubin 
X 
X 
 
X 
 
 
X 
 
 
 
X 
 
Amylase, lipase, CRP 
X 
X 
 
X 
 
 
X 
 
 
 
X 
 
Blood cell ABO 
phenotyping (minor 
antigens)15 
X ------------→  
 
 
 
 
 
 
 
 
 
 
Type and screen 
(ABO/rhesus) 15 
X ------------→ 
 
 
 
 
 
 
 
 
 
 
Direct Antiglobulin Test 
(DAT) [direct Coombs 
test]15 
X -------------→ 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
Correlative Exploratory Biology Studies 
 
 
 
Tumor tissue specimen19 
 
X 
X - As available 
 
 
Blood samples18 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Bone marrow aspirate21 
X -------------→ 
 
 
 
 
End of Cycle 2, 4, 8 and 12  
X 
 
 
 

                              
 
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1  
Arm A included the priming dose plus single agent Safety Lead-In conducted over 21 days, then treatment cycles (21-day cycle) begin. Cycles may be repeated as long 
as the patient does not have unacceptable toxicity (see Section 6.3 or Section Error! Reference source not found.) or disease progression to a maximum of 12 cycles.  
2  
Standard medical history is acceptable. Following screening, updates to medical history should be recorded. 
3 
Prior and concomitant medications – All medications taken within 21 days prior to treatment initiation and all new medications, including all medications for AEs, 
taken up to 30 days after treatment discontinuation should be recorded.  
4  
Hu5F9-G4 (magrolimab) will be administered as a priming dose, single agent Safety Lead-In and Day 1 of every week of every 3 week Cycles as outlined in Section 
6.2. A premedication regimen (oral acetaminophen and diphenhydramine, or comparable regimen) is required before the initial doses of Hu5F9-G4 (magrolimab) and 
in case of re-priming of the patient after > 4 weeks interruption in treatment.  
5 
Dinutuximab will be administered on Days 2-5 during the first week of every cycle as specified in Section 6.2. Administer antihistamines, antipyretics (i.e., 
acetaminophen and ibuprofen) and analgesia prior to each dinutuximab infusion as per Section 6.2. 
6  
Both height and weight will be recorded at screening. Only weight will be recorded at subsequent applicable visits.  
7 
A complete physical examination as well as a cancer-specific physical exam will be performed at screening. Physical exams at subsequent applicable visits will be 
targeted based on the investigator’s clinical observations and symptomatology. If a physical exam is performed within 3 days prior to a subsequent dosing day it does 
not need to be repeated on the dosing day provided there is no new status change.  
8  
Vital signs = heart rate, respiratory rate, blood pressure, temperature, pulse oximetry. See Section 6.2.1.3 and 6.2.1.4 for collection timepoints during and after infusion. 
Vital signs must also be collected at each non-dosing visit.  
9  
Karnofsky score of ≥50% is required for patients >16 years, and Lansky score of ≥50% is required for patients ≤16 years. Patients unable to walk due to paralysis, but 
who are using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. See APPENDIX A.  
10  Baseline disease evaluation will occur within 28 days of treatment initiation. During the treatment period Cycles 1 through 4, patients should be re-evaluated for 
response at the end of Cycles 2 and 4. After Cycle 4, disease evaluation will occur every 12 weeks (after every 4 cycles). Disease evaluations should occur within 7 
days prior to dosing of the subsequent cycle. If treatment is delayed, disease evaluations will follow the originally scheduled calendar dates and should not be adjusted 
for the dose delay. The same method of assessment and technique should be used throughout the study. See Section 12 for disease parameters, methods of assessment, 
and response criteria. For patients with neuroblastoma/ganglioneuroblastoma, bilateral bone marrow aspirates and trephine biopsies are required at all disease assessment 
time points (see Section 12.2) and Follow-up Visits for disease evaluation. 
11  Confirmatory scans should also be performed according to Section 12 in patients with measurable disease. The same method of assessment and technique should be 
used throughout the study. 
12  All AEs occurring within 30 days after the last dose of the study drug must be reported in a routine manner using Rave. Additionally, all AEs that occur within 30 days 
after the last dose of the study drug, regardless of causality, meeting the expedited reporting criteria outlined in Section 10.3 must also be reported expeditiously via 
CTEP-AERS. 
13 
All clinical laboratory tests must be performed in a licensed laboratory according to local policy. Pregnancy tests may be performed at the site using a licensed test. 
Laboratory results outside the limits of eligibility may be repeated to confirm eligibility and must be within the limits of eligibility before treatment initiation. Clinical 
laboratory tests conducted during screening do not need to be repeated on C1D1 if completed within 7 days prior to treatment initiation. All clinical laboratory tests 
during the treatment period must be performed within 72 hours prior to dosing. If treatment is delayed all clinical laboratory tests (and their respective windows) will 
adjust with the dose delay to reflect the patient’s clinical status at the time of dosing. 
14  Females of childbearing potential must have a negative urine or serum pregnancy test within 30 days of enrollment and within 72 hours prior to treatment initiation. 
Additional pregnancy tests (serum or urine) should be obtained throughout the study in accordance with local policy. 
15  Specimen must be drawn, completed, resulted and active per institutional guidelines prior to the Priming dose of Hu5F9-G4 (magrolimab). ABO, Rh, and DAT may 
be pan-reactive due to Hu5F9-G4 (magrolimab) binding to red cells (see Section 7.2.4).  

                              
 
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17  Upon treatment discontinuation, patients will complete the Safety Visit within 30 (±7) days, and Follow-up Visits at month 2 (± 1 week), month 4 (± 2 weeks), month 
6 (± 4 weeks), month 9 (± 4 weeks), and month 12 (± 2 months) and then yearly (± 2 months) until year 5, or until disease progression or until death, lost to follow-up, 
withdrawal of consent, or the end of the study, whichever occurs first. If a subsequent anti-cancer therapy is to be administered after treatment discontinuation but 
before the scheduled Safety Visit, the Safety Visit assessments should be conducted prior to the start of the new therapy if possible.  
• Follow-up Visits will be completed in-person unless the patient does not agree to continue in-person visits. In this case telephone contact may be arranged to 
ensure the collection of as many safety and efficacy parameters as possible. A patient that agrees to modified follow-up is not considered to have withdrawn 
consent or to have withdrawn from the study. 
• Patients removed from protocol therapy for unacceptable AE(s) will be followed until resolution or stabilization of the AE. In addition, these patients will 
complete the EOT, Safety, and Follow-up Visits according to protocol. 
18  
All blood draws for correlative exploratory biology studies will be performed according to the schedule outlined in Table 3, Specimen Collection Schedule; and Section 
5. All blood draws for correlative exploratory biology studies must be performed prior to dosing. If treatment is delayed, blood draws for correlative exploratory biology 
studies will follow the originally scheduled calendar dates and should not be adjusted for the dose delay. 
19  Archival slides will be requested from all patients. If available, clinical biopsies or surgical samples obtained during treatment or at disease progression will be requested.  
20   After Cycle 2, Hu5F9-G4 (magrolimab) will be administered ONLY on Day 1 of week 1 and 3 only (week 2 will be a week of rest).  
21 
Bone marrow aspirations will be conducted in all patients with neuroblastoma/ganglioneuroblastoma (as per INRC). Week 1, Day 1 collection is mandatory, except if 
viably frozen bone marrow aspirate collected within 4 weeks (28 days) of the Priming dose (Week 1, Day 1) is available and can be provided to the EET Biobank. Bone 
marrow aspirates are required at all disease assessment timepoints (end of Cycle 2, 4, 8 and 12). Bone marrow aspirate at End of Therapy is optional.  
22 
Within 24 hours prior to the Priming dose (Week 1) of Hu5F9-G4, hemoglobin must be ≥ 9.5 g/dL. Within 24 hours prior to the first full dose (Week 2) of Hu5F9-G4, 
hemoglobin must be ≥ 9.0 g/dL (see Section 6.2.1.3). Hemoglobin must be checked 3 to 6 hours after the initiation of the first and second doses of Hu5F9-G4 
(magrolimab).  
 
 
 
 
 
 

                              
 
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Baseline/screening evaluations are to be conducted within 4 weeks (28 days) prior to start of protocol therapy. Scans must be done < 4 weeks (28 days) prior 
to the start of protocol therapy. In the event that the patient’s condition is deteriorating, laboratory evaluations should be repeated within 48 hours prior to 
initiation of the next cycle of therapy. 
 
EXPANSION COHORTS (ARM B) – Priming and Treatment Cycles1 
Treatment Cycles/Visits 
Screening 
Treatment 
Follow Up 
Priming 
Cycle 1 
Cycle 2 and subsequent cycles    
End of 
Therapy 
Safety 
Follow Up17 
Week 1 
Week 2 
Weeks 3-4 
Week 1 
Weeks 2-320 
Scheduling Window 
Within 28 
days 
Day 1 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Within 10 
days after last 
IP dose 
30 days after 
last IP dose 
±7 days 
Month 2, 4, 6, 9, 
12 and annually 
(Year 2-5) 
Administrative Procedures 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility evaluation 
X 
 
 
 
 
 
 
 
 
 
 
Medical history2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Treatment 
Hu5F9-G4 (magrolimab) 
administration4 
 
X 
X 
 
X 
X 
 
X20 
 
 
 
Dinutuximab 
administration5 
 
 
 
X 
 
 
X 
 
 
 
 
Clinical Assessments 
Height, weight6 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
Physical exam7 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
Vital signs8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
ECHO, MUGA or Cardiac 
MRI 
X 
 
 
 
 
 
 
 
 
 
 
Performance status9 
X 
X 
X 
 
 
X 
 
 
 
X 
X 
Disease evaluation10 
X 
 
End of Cycle 2 and 4, and then after every 4 cycles 
 
 
X 
Confirmatory imaging11 
 
As per Section Error! Reference source not found. 
Bone marrow aspiration 
and biopsy if 
NBL/ganglioneuroblastoma 
10, 21 
X ------------→ 
End of Cycle 2 and 4, and then after every 4 cycles 
 
 
X 
AE and SAE evaluation12 
 
Continuously 
Clinical Laboratory Tests13 

                              
 
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EXPANSION COHORTS (ARM B) – Priming and Treatment Cycles1 
Treatment Cycles/Visits 
Screening 
Treatment 
Follow Up 
Priming 
Cycle 1 
Cycle 2 and subsequent cycles    
End of 
Therapy 
Safety 
Follow Up17 
Week 1 
Week 2 
Weeks 3-4 
Week 1 
Weeks 2-320 
Scheduling Window 
Within 28 
days 
Day 1 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Day 1 
±2 days 
Day 2-5 
±2 days 
Day 1 
±2 days 
Within 10 
days after last 
IP dose 
30 days after 
last IP dose 
±7 days 
Month 2, 4, 6, 9, 
12 and annually 
(Year 2-5) 
Pregnancy test14 
X 
As required locally 
CBC with differential and 
platelets 
X 
X22 
X22 
 
 
X 
 
 
 
X 
 
Electrolytes, creatinine, 
urea (BUN), Ca2+, PO43-, 
Mg2+ 
X 
X 
X 
 
 
X 
 
 
 
X 
 
ALT, AST, bilirubin 
X 
X 
X 
 
 
X 
 
 
 
X 
 
Amylase, lipase, CRP 
X 
X 
X 
 
 
X 
 
 
 
 
 
Blood cell ABO 
phenotyping (minor 
antigens)15 
X ------------→ 
 
 
 
 
 
 
 
 
 
Type and screen 
(ABO/rhesus)15 
X ------------→  
 
 
 
 
 
 
 
 
 
Direct Antiglobulin Test 
(DAT) [direct Coombs test] 
X ------------→ 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
Correlative Exploratory Biology Studies 
Tumor tissue specimen19 
X 
X - As available 
 
 
Blood samples18 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Bone marrow aspirate21 
X ------------→ 
 
 
 
End of Cycle 2, 4, 8 and 12 
X 
 
 
1  
Arm B patients will receive the priming dose followed by Cycle 1 and 2 (each 21 days). Cycles may be repeated as long as the patient does not have unacceptable 
toxicity (see Section 6.3 or Section Error! Reference source not found.) or disease progression to a maximum of 12 cycles for patients in cohorts B1, B2 and B3 and to 
a maximum of 5 cycles post resection for patients in cohort B4. 
2  
Standard medical history is acceptable. Following screening, updates to medical history should be recorded. 
3 
Prior and concomitant medications – All medications taken within 21 days prior to treatment initiation and all new medications, including all medications for AEs, 
taken up to 30 days after treatment discontinuation should be recorded.  
4  
Hu5F9-G4 (magrolimab) will be administered as a priming dose, single agent Safety Lead-In and Day 1 of every week of every 3 week Cycles as outlined in Section 
6.2. A premedication regimen (oral acetaminophen and diphenhydramine, or comparable regimen) is required before the initial doses of Hu5F9-G4 (magrolimab) and 
in case of re-priming of the patient after > 4 weeks interruption in treatment.  

                              
 
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5 
Dinutuximab will be administered on Days 2-5 during the first week of every cycle as specified in Section 6.2. Administer antihistamines, antipyretics (i.e. 
acetaminophen and ibuprofen) and analgesia prior to each dinutuximab infusion as per Section 6.2. 
6  
Both height and weight will be recorded at screening. Only weight will be recorded at subsequent applicable visits.  
7 
A complete physical examination as well as a cancer-specific physical exam will be performed at screening. Physical exams at subsequent applicable visits will be 
targeted based on the investigator’s clinical observations and symptomatology. If a physical exam is performed within 3 days prior to a subsequent dosing day it does 
not need to be repeated on the dosing day provided there is no new status change.  
8  
Vital signs = heart rate, respiratory rate, blood pressure, temperature, pulse oximetry. See Sections 6.2.1.3 and 6.2.1.4 for collection timepoints during and after infusion. 
Vital signs must also be collected at each non-dosing visit.  
9  
Karnofsky score of ≥50% is required for patients >16 years, and Lansky score of ≥50% is required for patients ≤16 years. Patients unable to walk due to paralysis, but 
who are using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. See APPENDIX A. 
10  Baseline disease evaluation will occur within 28 days of treatment initiation. During the treatment period Cycles 1 through 4, patients in Cohorts B1, B2 and B3 should 
be re-evaluated for response at the end of Cycles 2 and 4. After Cycle 4, disease evaluation will occur every 12 weeks (after every 4 cycles). Disease evaluations should 
occur within 7 days prior to dosing of the subsequent cycle. If treatment is delayed, disease evaluations will follow the originally scheduled calendar dates and should 
not be adjusted for the dose delay. The same method of assessment and technique should be used throughout the study. See Section 12 for disease parameters, methods 
of assessment, and response criteria. Cohort B4 – refer to Section 12 for disease evaluation timepoints.  For patients with neuroblastoma/ganglioneuroblastoma, bilateral 
bone marrow aspirates and trephine biopsies are required at all disease assessment time points (see Section 12.2) and Follow-up Visits for disease evaluation. 
11  Confirmatory scans should also be performed according to Section 12 in patients with measurable disease. The same method of assessment and technique should be 
used throughout the study.  
12  All AEs occurring within 30 days after the last dose of the study drug must be reported in a routine manner using Rave. Additionally, all AEs that occur within 30 days 
after the last dose of the study drug, regardless of causality, meeting the expedited reporting criteria outlined in Section 10.3 must also be reported expeditiously via 
CTEP-AERS. 
13 
All clinical laboratory tests must be performed in a licensed laboratory according to local policy. Pregnancy tests may be performed at the site using a licensed test. 
Laboratory results outside the limits of eligibility may be repeated to confirm eligibility and must be within the limits of eligibility before treatment initiation. Clinical 
laboratory tests conducted during screening do not need to be repeated on C1D1 if completed within 7 days prior to treatment initiation. All clinical laboratory tests 
during the treatment period must be performed within 72 hours prior to dosing. If treatment is delayed all clinical laboratory tests (and their respective windows) will 
adjust with the dose delay to reflect the patient’s clinical status at the time of dosing. 
14  Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to treatment initiation. Additional pregnancy tests (serum 
or urine) should be obtained throughout the study in accordance with local policy. 
15.      Specimen must be drawn, completed, resulted and active per institutional guidelines prior to the Priming dose of Hu5F9-G4 (magrolimab). ABO, Rh, and DAT may 
be pan-reactive due to Hu5F9-G4 (magrolimab) binding to red cells (see Section 7.2.4).  
17  Upon treatment discontinuation, patients will complete the Safety Visit within 30 (±7) days, and Follow-up Visits at month 2 (± 1 week), month 4 (± 2 weeks), month 
6 (± 4 weeks), month 9 (± 4 weeks), and month 12 (± 2 months) and then yearly (± 2 months) until year 5, or until disease progression or until death, lost to follow-up, 
withdrawal of consent, or the end of the study, whichever occurs first. If a subsequent anti-cancer therapy is to be administered after treatment discontinuation but 
before the scheduled Safety Visit, the Safety Visit assessments should be conducted prior to the start of the new therapy if possible.  
- 
Follow-up Visits will be completed in-person unless the patient does not agree to continue in-person visits. In this case telephone contact may be arranged to ensure 
the collection of as many safety and efficacy parameters as possible. A patient that agrees to modified follow-up is not considered to have withdrawn consent or to 
have withdrawn from the study. 

                              
 
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- 
Patients removed from protocol therapy for unacceptable AE(s) will be followed until resolution or stabilization of the AE. In addition, these patients will complete 
the EOT, Safety, and Follow-up Visits according to protocol. 
18  
All blood draws for correlative exploratory biology studies will be performed according to the schedule outlined in Table 3, Specimen Collection Schedule; and Section 
5. All blood draws for correlative exploratory biology studies must be performed prior to dosing. If treatment is delayed, blood draws for correlative exploratory biology 
studies will follow the originally scheduled calendar dates and should not be adjusted for the dose delay.  
19   Archival slides will be requested from all patients. If available, clinical biopsies or surgical samples obtained during treatment or at disease progression will be requested. 
Cohort B4 - Pulmonary metastases resected from staged resection at enrollment and then after one cycle of protocol therapy OR if only one resection performed, tissue 
will be requested at enrollment after surgical metastasectomy. 
20  
After Cycle 2, Hu5F9-G4 (magrolimab) will be administered ONLY on Day 1 of week 1 and week 3 (week 2 will be a week of rest). 
21 
Bone marrow aspirations will be conducted in all patients with neuroblastoma (as per INRC). Week 1, Day 1 collection is mandatory, except if viably frozen bone 
marrow aspirate collected within 4 weeks (28 days) of the Priming Dose (Week 1, Day 1) is available and can be provided to the EET Biobank. Bone marrow aspirates 
are required at all disease assessment timepoints (end of Cycle 2, 4, 8 and 12). Bone marrow aspirate at End of Therapy is optional.  
22 
Within 24 hours prior to the Priming dose (Week 1) of Hu5F9-G4, hemoglobin must be ≥ 9.5 g/dL. Within 24 hours prior to the first full dose (Week 2) of Hu5F9-G4, 
hemoglobin must be ≥ 9.0 g/dL (see Section 6.2.1.3). Hemoglobin must be checked 3 to 6 hours after the initiation of the first and second doses of Hu5F9-G4 
(magrolimab). 
 
 
 
 
 
 
 
 
 
 
 

                              
 
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12 
EVALUATION CRITERIA 
 
Although the clinical benefit of the combination of Hu5F9-G4 (magrolimab) and dinutuximab has not yet been established, 
the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully 
monitored for tumor response and symptom relief in addition to safety and tolerability. Patients with measurable disease 
will be assessed by standard criteria as outlined below.  
 
For Arm A and Arm B cohorts 1-3, patients should be evaluated for disease status initially after Cycle 2 and Cycle 4 then 
after every four cycles of combination therapy, for a maximum of 12 cycles in cohorts 1 through 3. After completion of 
combination therapy, for patients who have not experienced disease progression, disease evaluations will continue at month 
2 (± 1 week), month 4 (± 2 weeks), month 6 (± 4 weeks), month 9 (± 4 weeks), and month 12 (± 2 months) and then every 
six months (± 2 months) until year 5. Confirmatory scans will also be obtained ≥ 4 weeks following initial documentation 
of an objective response.  
 
Patients in Arm B cohort 4, who undergo resection of all metastatic lesions (rendered NED) before protocol treatment, 
should be evaluated for disease status after Cycle 2 and after Cycle 5. After Cycle 5 for patients who have not experienced 
disease progression, disease evaluation will continue at month 2 (± 1 week), month 4 (± 2 weeks), month 6 (± 4 weeks), 
month 9 (± 4 weeks), and month 12 (± 2 months) and then every six months (± 2 months) until year 5.  
 
Patients in Arm B cohort 4, who undergo staged resection during protocol therapy, should be evaluated for baseline disease 
status after their initial resection (prior to Priming Dose and Cycle 1). The subsequent disease evaluations will be performed 
following the second surgical resection and completion of two cycles (i.e., end of Cycle 3), and after five cycles (i.e., end 
of Cycle 6) of combination therapy. After Cycle 6 for patients who have not experienced disease progression, disease 
evaluation will continue at month 2 (± 1 week), month 4 (± 2 weeks), month 6 (± 4 weeks), month 9 (± 4 weeks), and month 
12 (± 2 months) and then every six months (± 2 months) until year 5. 
 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All baseline evaluations should 
be performed as closely as possible to the beginning of treatment and never more than 4 weeks (within 28 days) before the 
beginning of the treatment. 
 
The same method of assessment and the same technique should be used to characterize each identified and reported lesion 
at baseline and during follow-up. Imaging-based evaluation is preferred to evaluation by clinical examination unless the 
lesion(s) being followed cannot be imaged but are assessable by clinical exam. 
 
12.1 
Antitumor Effect – Osteosarcoma (Measurable disease) 
 
Response and progression will be evaluated in this study using the new international criteria proposed by the revised 
Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].  Changes in 
the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant 
lymph nodes are used in the RECIST criteria. 
 
12.1.1 Definitions 
 
Evaluable for toxicity.  All patients will be evaluable for toxicity from the time of their first treatment with Hu5F9-
G4 (magrolimab) (Safety Lead-In). 
 
Evaluable for objective response.  Patients must have measurable osteosarcoma at enrollment for the expansion 
cohort with osteosarcoma (Cohort B3). Those patients who have only received the priming dose and have received 
at least one dose of Hu5F9-G4 (magrolimab) followed on day 2 by dinutuximab and who do not have their disease 

                              
 
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re-evaluated will be considered non-evaluable. 
 
Note: Patients who exhibit disease progression prior to end of Cycle 2 evaluation will be considered evaluable. 
 
12.1.2 Disease Parameters 
 
Measurable disease.  Measurable lesions are defined as those that can be accurately measured in at least one 
dimension (longest diameter to be recorded) as ≥10 mm (≥1 cm) with cross sectional imaging (CT scan or MRI), 
or calipers by clinical exam.  All tumor measurements must be recorded in millimeters (or decimal fractions of 
centimeters). 
 
Note:  Tumor lesions that are situated in a previously irradiated area might be considered measurable.   
 
Malignant lymph nodes.  To be considered pathologically enlarged and measurable, a lymph node must be ≥15 mm 
(≥1.5 cm) in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 
mm [0.5 cm]).  At baseline and in follow-up, only the short axis will be measured and followed. 
 
Non-measurable disease.  All other lesions (or sites of disease), including small lesions (longest diameter <10 mm 
[<1 cm] or pathological lymph nodes with ≥10 to <15 mm [≥1 to <1.5 cm] short axis), are considered non-
measurable disease.  Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by CT or MRI), are considered 
as non-measurable. 
 
Note: Cystic lesions that meet the criteria for radiographically defined simple cysts should not be considered as 
malignant lesions (neither measurable nor non-measurable) since they are, by definition, simple cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, if they meet the 
definition of measurability described above. However, if non-cystic lesions are present in the same patient, these 
are preferred for selection as target lesions. 
Target lesions.  All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, representative 
of all involved organs, should be identified as target lesions and recorded and measured at baseline.  Target lesions 
should be selected on the basis of their size (lesions with the longest diameter), be representative of all involved 
organs, but in addition should be those that lend themselves to reproducible repeated measurements.  It may be the 
case that, on occasion, the largest lesion does not lend itself to reproducible measurement in which circumstance 
the next largest lesion which can be measured reproducibly should be selected.  A sum of the diameters (longest for 
non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculated and reported as the baseline 
sum diameters.  If lymph nodes are to be included in the sum, then only the short axis is added into the sum.  The 
baseline sum diameters will be used as reference to further characterize any objective tumor regression in the 
measurable dimension of the disease. 
 
Non-target lesions.  All other lesions (or sites of disease) including any measurable lesions over and above the 5 
target lesions should be identified as non-target lesions and should also be recorded at baseline.  Measurements of 
these lesions are not required, but the presence, absence, or in rare cases unequivocal progression of each should be 
noted throughout follow-up.  
 
12.1.3 Methods for Evaluation of Measurable Disease 
 
Clinical lesions:  Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules 
and palpable lymph nodes) and ≥10 mm (≥1 cm) diameter as assessed using calipers (e.g., skin nodules).  In the 

                              
 
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case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is 
recommended.  
 
Conventional CT and MRI:  This guideline has defined measurability of lesions on CT scan based on the assumption 
that CT slice thickness is 5 mm (0.5 cm) or less.  If CT scans have slice thickness greater than 5 mm (0.5 cm), the 
minimum size for a measurable lesion should be twice the slice thickness.  MRI is also acceptable.   
 
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and temporal resolution; however, there 
are many image acquisition variables involved in MRI, which greatly impact image quality, lesion conspicuity, and 
measurement.  Furthermore, the availability of MRI is variable globally.  As with CT, if an MRI is performed, the 
technical specifications of the scanning sequences used should be optimized for the evaluation of the type and site 
of disease.  Furthermore, as with CT, the modality used at follow-up should be the same as was used at baseline 
and the lesions should be measured/assessed on the same pulse sequence.  It is beyond the scope of the RECIST 
guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body parts, and diseases.  Ideally, 
the same type of scanner should be used and the image acquisition protocol should be followed as closely as possible 
to prior scans.  Body scans should be performed with breath-hold scanning techniques, if possible. 
 
PET-CT:  At present, the low dose or attenuation correction CT portion of a combined PET-CT is not always of 
optimal diagnostic CT quality for use with RECIST measurements.  However, if the site can document that the CT 
performed as part of a PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then 
the CT portion of the PET-CT can be used for RECIST measurements and can be used interchangeably with 
conventional CT in accurately measuring cancer lesions over time.  Note, however, that the PET portion of the CT 
introduces additional data which may bias an investigator if it is not routinely or serially performed.   
 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be used as a method of 
measurement.  Ultrasound examinations cannot be reproduced in their entirety for independent review at a later 
date and, because they are operator dependent, it cannot be guaranteed that the same technique and measurements 
will be taken from one assessment to the next.  If new lesions are identified by ultrasound in the course of the study, 
confirmation by CT or MRI is advised.  If there is concern about radiation exposure at CT, MRI may be used instead 
of CT in selected instances. 
 
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor evaluation is not advised.  
However, such techniques may be useful to confirm complete pathological response when biopsies are obtained or 
to determine relapse in trials where recurrence following complete response (CR) or surgical resection is an 
endpoint. 
 
Tumor Markers:  Tumor markers alone cannot be used to assess response.  If markers are initially above the upper 
normal limit, they must normalize for a patient to be considered in complete clinical response.   
 
Cytology, Histology  These techniques can be used to differentiate between partial responses (PR) and complete 
responses (CR) in rare cases (e.g., residual lesions in tumor types, such as germ cell tumors, where known residual 
benign tumors can remain). 
 
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens during treatment when 
the measurable tumor has met criteria for response or stable disease is mandatory to differentiate between response 
or stable disease (an effusion may be a side effect of the treatment) and progressive disease. 
 
FDG-PET  While FDG-PET response assessments need additional study, it is sometimes reasonable to incorporate 
the use of FDG-PET scanning to complement CT or MRI scanning in assessment of progression (particularly 

                              
 
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possible 'new' disease).  New lesions on the basis of FDG-PET imaging can be identified according to the following 
algorithm:  
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the positive FDG-PET at follow-up 
corresponds to a new site of disease confirmed by CT, this is PD.  If the positive FDG-PET at follow-up is not 
confirmed as a new site of disease on CT, additional follow-up CT scans are needed to determine if there is 
truly progression occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-PET 
scan).  If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT that is not 
progressing on the basis of the anatomic images, this is not PD. 
c. FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy in cases where a residual 
radiographic abnormality is thought to represent fibrosis or scarring.  The use of FDG-PET in this circumstance 
should be prospectively described in the protocol and supported by disease-specific medical literature for the 
indication.  However, it must be acknowledged that both approaches may lead to false positive CR due to 
limitations of FDG-PET and biopsy resolution/sensitivity. 
 
Note:  A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake greater than twice that of 
the surrounding tissue on the attenuation corrected image. 
 
12.1.4 Response Criteria 
 
12.1.4.1 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. 
 
12.1.4.2 Evaluation of Non-Target Lesions 
 
Complete Response (CR):  Disappearance of all non-target lesions and normalization of tumor marker level.  
All lymph nodes must be non-pathological in size (<10 mm [<1 cm] short axis). 
 
Note:  If tumor markers are initially above the upper normal limit, they must normalize for a patient to be 
considered in complete clinical response. 
 
Non-CR/Non-PD:  Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level 
above the normal limits. 
 
Progressive Disease (PD):  Appearance of one or more new lesions and/or unequivocal progression of existing 
non-target lesions.  Unequivocal progression should not normally trump target lesion status.  It must be 

                              
 
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representative of overall disease status change, not a single lesion increase. 
 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating physician 
should prevail in such circumstances, and the progression status should be confirmed at a later time by the 
review panel (or Principal Investigator). 
 
12.1.4.3 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. 
 
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. 
 
12.2 
Response Criteria for Patients with Neuroblastoma (measurable or evaluable disease) 
 
This study will use the revised International Neuroblastoma Response Criteria (INRC) for disease assessment (Park et al., 
2017). The updated response criteria incorporate current approaches to imaging of neuroblastoma, including functional 
imaging. Furthermore, a standardized approach to assessment of bone marrow involvement is included. The current INRC 
do not include methods of disease assessment that are less sensitive and/or specific for neuroblastoma (99Tc bone scan and 
catecholamine levels). 
 
12.2.1 Definitions 
 
Evaluable for toxicity: All patients will be evaluable for toxicity from the time of their first treatment with Hu5F9-
G4 (magrolimab) (Safety Lead-In). 
 

                              
 
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Evaluable for Response: Patients must have evaluable or measurable malignant disease at enrollment for the dose 
escalation cohorts, and patients enrolling in the expansion cohort with neuroblastoma must have measurable OR 
MIBG evaluable disease at enrollment. MIBG evaluable disease for eligibility in neuroblastoma is defined as MIBG 
scan obtained within 3 weeks prior to study entry with positive uptake at a minimum of one site.  
 
Those patients who have only received the priming dose and have received at least one dose of Hu5F9-G4 
(magrolimab) followed on day 2 by dinutuximab and who do not have their disease re-evaluated will be considered 
non-evaluable.   
 
Note:  Patients who exhibit disease progression prior to the disease evaluation will also be considered evaluable. 
 
12.2.2 Disease Parameters 
 
Measurable disease: Measurable lesions are defined as those that can be accurately measured in at least one 
dimension (longest diameter to be recorded) as ≥ 10 mm with cross sectional imaging (CT scan or MRI), or ≥ 10 
mm with calipers by clinical exam. All tumor measurements must be recorded in millimeters (or decimal fractions 
of centimeters).  
 
Note: Tumor lesions that are situated in a previously irradiated area will be considered measurable if they 
demonstrate clear evidence of progression after completion of radiation.  
 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node must be ≥ 15 mm 
in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At 
baseline and in follow-up, only the short axis will be measured and followed as per RECIST 1.1 criteria. Patients 
with neuroblastoma may have conglomerate masses of non-discrete lymph nodes (i.e. multiple contiguous 
retroperitoneal nodes). When a short axis of a discreet node cannot be identified, a lymph node conglomerate can 
be measured using the longest diameter of the composite lesion. Tracer avidity of metastatic nodes will be recorded 
at baseline and during disease evaluations.  
 
Non-measurable disease: All other lesions (or sites of disease), including small lesions (longest diameter < 10 mm 
or pathological lymph nodes with ≥ 10 to < 15 mm short axis), are considered non-measurable disease. Bone lesions, 
leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast 
disease, and abdominal masses (not followed by CT or MRI), are considered as non-measurable.  
 
Note: Cystic lesions that meet the criteria for radiographically defined simple cysts should not be considered as 
malignant lesions (neither measurable nor non-measurable) since they are, by definition, simple cysts.  
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, if they meet the 
definition of measurability described above. However, if non-cystic lesions are present in the same patient, these 
are preferred for selection as target lesions. 
 
Target lesions: All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, representative 
of all involved organs, should be identified as target lesions and recorded and measured at baseline. Target lesions 
should be selected on the basis of their size (lesions with the longest diameter), be representative of all involved 
organs, but in addition should be those that lend themselves to reproducible repeated measurements. It may be the 
case that, on occasion, the largest lesion does not lend itself to reproducible measurement in which circumstance 
the next largest lesion which can be measured reproducibly should be selected. For the purposes of response 
assessment, target lesions are disease sites that are measurable (non-nodal soft tissue mass ≥ 10 mm in longest 
dimension or lymph node ≥ 15 mm in short axis) and tracer avid OR are biopsy positive for neuroblastoma or 
ganglioneuroblastoma. The sum of diameters of target lesions is defined as the sum of the short axis of discrete 

                              
 
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lymph nodes (i.e., cervical, axillary nodes) added to the sum of the longest diameters of non-lymph node soft tissue 
metastases. The baseline sum diameters will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease.  
 
Non-target lesions: All other lesions (or sites of disease) including any measurable lesions over and above the 5 
target lesions should be identified as non-target lesions and should also be recorded at baseline. Measurements of 
these lesions are not required, but the presence, absence, or in rare cases unequivocal progression of each should be 
noted throughout follow-up. 
 
Bone lesions: Osteomedullary disease will be assessed using 123I-MIBG scans or FDG-PET scans. Technetium 
bone scans are no longer used as part of the revised INRC and are not included as part of disease reassessments 
during this trial. The extent of tracer avid disease will be evaluated using the Curie scoring system. SPECT may be 
used to confirm the presence or absence of lesions in a given segment of the body. The absolute Curie score should 
be reported at baseline. A relative score (Curie score at the time of disease assessment divided by baseline Curie 
score) should be recorded at the time of each disease evaluation.  
 
Bone marrow disease: Bilateral bone marrow aspirates and trephine biopsies are required at disease assessment time 
points (see Section 11). The extent of marrow involvement in all four samples should be recorded. Use of 
immunohistochemical staining for evaluation of trephine biopsies is strongly encouraged. The percentage of tumor 
infiltration of bone marrow space assessed by histologic evaluation of trephine/biopsies or counting the number of 
tumor cells in aspirates by cytology or immunocytology (recommended if available) divided by the number of 
hematopoietic/mononuclear cells evaluated to obtain a percentage involvement (methodology described by Burchill 
et al.)(Burchill et al., 2017). The bone marrow sample with the highest percentage of tumor infiltration is used for 
response assessment. If > 0% to ≤ 5% tumor infiltration is the highest percentage seen among samples obtained, the 
result should be recorded as minimal marrow disease. 
 
12.2.3 Response Criteria  
 
PRIMARY (SOFT TISSUE) TUMOR RESPONSE1 
 
RESPONSE 
ANATOMICAL IMAGING & MIBG (FDG-PET2) IMAGING 
Complete Response (CR) 
• 
< 10 mm residual soft tissue at primary site, 
AND 
• 
Complete resolution of MIBG or FDG-PET2 uptake (for MIBG 
non-avid tumors) at primary site  
Partial Response (PR) 
• 
≥ 30% decrease in longest diameter (LD) of primary site  
• 
MIBG or FDG-PET2 uptake at primary site stable, improved or 
resolved  
Progressive Disease (PD) 
• 
20% increase in longest diameter taking as reference the smallest 
sum on study (this includes the baseline sum if that is the smallest 
on study),  
AND  
• 
a minimum absolute increase of 5 mm in longest dimension3  
Stable Disease (SD) 
• 
Neither sufficient shrinkage for PR nor sufficient 
1 Not for use in assessment of metastatic sites 
2 For 123 I-MIBG non-avid tumors 
3 A mass that has not met PD measurement criteria but has fluctuating 123I-MIBG avidity will not be considered progressive 

                              
 
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disease. 
 
 
RESPONSE AT METASTATIC SOFT TISSUE AND BONE SITES 
 
RESPONSE 
ANATOMICAL IMAGING & MIBG (FDG-PET1) IMAGING 
Complete Response (CR) 
Resolution of all sites of disease defined as:  
• 
Non-primary target and non-target lesions measure < 10 mm  
AND  
• 
Lymph nodes identified as target lesions decrease to a short axis 
< 15 mm,  
AND  
• 
MIBG uptake or FDG-PET1 uptake (for MIBG non-avid tumors) 
of non-primary lesions resolves completely  
Partial Response (PR) 
• 
≥ 30% decrease in sum of diameters2 of non-primary target lesions 
compared to baseline, AND all of the following:  
o 
Non-target lesions may be stable or smaller in size AND  
o 
No new lesions AND  
o 
≥ 50% reduction in MIBG absolute bone score (Relative 
MIBG bone score ≥ 0.1 to ≤ 0.5) or ≥ 50% reduction in 
number of FDG-PET1 avid bone lesions3,4  
Progressive Disease (PD) 
Any of the following:  
• 
Any new soft tissue lesion detected by CT or MRI that is also 
MIBG avid or FDG-PET avid;  
• 
Any new soft tissue lesion seen on anatomic imaging that is 
biopsied and confirmed to be a neuroblastoma;  
• 
Any new bone site that is MIBG avid;  
• 
A new bone site that is FDG-PET1 avid (for MIBG non-avid 
tumors) AND has CT or MRI findings consistent with tumor OR 
has been confirmed histologically to be neuroblastoma;  
• 
> 20% increase in longest diameter taking as reference the 
smallest sum on study (this includes the baseline sum if that is the 
smallest on study), AND a minimum absolute increase of 5 mm 
in sum of diameters of target soft tissue lesions;  
• 
Relative MIBG score ≥ 1.24  
Stable Disease (SD) 
Neither sufficient shrinkage for PR nor sufficient increase for PD of non-
primary lesions  
1 Used for MIBG non-avid tumors  
2 Sum of diameters is defined as the sum of the short axis of discrete lymph nodes (i.e., cervical, axillary nodes) added to the sum of the 
longest diameters of non-lymph node soft tissue metastases. Masses of conglomerate non-discrete lymph nodes will be measured using 
longest diameter.  
3 For patients with soft tissue metastatic disease, resolution of MIBG and/or FDG-PET uptake at the soft tissue sites is not required; all 
size reduction criteria must be fulfilled.  
4 Relative Curie score is the absolute score for bone lesions at time of response assessment divided by the absolute score for bone lesions 
at entry onto a clinical trial. MIBG-SPECT or MIBG-SPECT/CT may be used for scoring purposes, but the same imaging methodology 
should be used for all evaluations. 
 
BONE MARROW RESPONSE 
  

                              
 
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RESPONSE 
BONE MARROW STATUS1 
Complete Response (CR) 
Bone marrow with no tumor infiltration upon reassessment, independent 
of baseline tumor involvement  
Progressive Disease (PD) 
Any of the following:  
• 
Bone marrow without tumor infiltration that becomes > 5% tumor 
infiltration upon reassessment; or  
• 
Bone marrow with tumor infiltration that increases by > 2-fold 
and has > 20% tumor infiltration upon reassessment.  
Minimal Disease (MD) 
Any of the following:  
• 
Bone marrow with ≤ 5% tumor infiltration and remains > 0-≤ 5% 
tumor infiltration upon reassessment; or  
• 
Bone marrow with no tumor infiltration that becomes ≤ 5% tumor 
infiltration upon reassessment; or  
• 
Bone marrow with >20% tumor infiltration that has > 0-≤ 5% 
tumor infiltration upon reassessment.  
Stable Disease (SD) 
Bone marrow with tumor infiltration that remains positive with > 5% 
tumor infiltration upon reassessment but does not meet CR, MD or PD 
criteria  
1 Immunohistochemistry strongly encouraged 
 
DETERMINATION OF OVERALL RESPONSE  
 
RESPONSE 
CRITERIA 
Complete Response (CR) 
All components meet criteria for CR  
 
Partial Response (PR) 
PR in at least one component and all other components are either CR, 
MD (Bone marrow), PR (Soft tissue or Bone) or Not involved (NI); no 
component with PD.  
 
Minor Response (MR) 
PR or CR in at least one component but at least one other component 
with SD; no component with PD.  
 
Stable Disease (SD) 
SD in one component with no better than SD or NI in any other 
component; no component with PD.  
 
Progressive Disease (PD) 
Any component with PD  
 
NI = Not involved, site not involved at study entry and remains not involved; MD = Minimal Disease, for bone marrow 
assessment only. 
 
12.2.4 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 recurrent or progressive disease is objectively 
documented (taking as reference for progressive disease the smallest measurements recorded since the treatment 
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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.  
 
13 
STUDY OVERSIGHT AND DATA REPORTING / REGULATORY REQUIREMENTS 
 
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 10 (Adverse Events: List and 
Reporting Requirements). 
 
13.1 
Data and Safety Monitoring Plan 
Data and safety is ensured by several integrated components including the Data and Safety Monitoring Committee. 
 
13.1.1 Data and Safety Monitoring Committee 
This study will be monitored in accordance with the Children’s Oncology Group PEP-CTN policy for data and 
safety monitoring of Phase 1 and 2 studies. In brief, the role of the COG PEP-CTN Data and Safety Monitoring 
Committee is to protect the interests of patients and the scientific integrity for all Phase 1 and 2 studies. The DSMC 
consists of a chair; a statistician external to COG; one external member; one consumer representative; the lead 
statistician of the PEP-CTN scientific committee; and a member from the NCI. The DSMC meets at least every 6 
months to review current study results, as well as data available to the DSMC from other related studies. 
Approximately 6 weeks before each meeting of the Phase 1 and 2 DSMC, study chairs will be responsible for 
working with the study statistician to prepare study reports for review by the DSMC. The DSMC will provide 
recommendations to the PEP-CTN Chair and the Group Chair for each study reviewed to change the study or to 
continue the study unchanged. Data and Safety Committee reports for institutional review boards can be prepared 
using the public data monitoring report as posted on the COG member’s Web site. 
 
13.1.2 Monitoring by the Study Chair and the Steering Committee 
The study chair will monitor the study regularly and enter evaluations of patients’ eligibility, evaluability, and dose 
limiting toxicities into the study database. In addition, study data and the study chair’s evaluations will be reviewed 
by the PEP-CTN Chair, Vice Chair and Statistician on a weekly conference call. 
 
 
13.2 
Data Submission / Data Reporting 
 
Data Mapping Utility (DMU) Reporting Complete 
Data for this study will be submitted via the Data Mapping Utility (DMU). Cumulative protocol- and patient-
specific data will be submitted weekly to CTEP electronically via the DMU.  DMU Complete reporting consists of 
Patient Demographics, Baseline Abnormalities, On/Off Treatment/Study Status, Treatment/Course/Dosing 
information, Adverse Events, Late Adverse Events, and Response data as applicable.  More information on the 
DMU is available on the CTEP Website: 
 https://ctep.cancer.gov/protocolDevelopment/dmu.htm. DMU reporting is not a responsibility of institutions 
participating in this trial. 
 
 
13.2.1 Data Quality Portal 
 

                              
 
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The Data Quality Portal (DQP) provides a central location for site staff to manage unanswered queries and form 
delinquencies, monitor data quality and timeliness, generate reports, and review metrics.  
The DQP is located on the CTSU members’ website under Data Management. The Rave Home section displays a 
table providing summary counts of Total Delinquencies and Total Queries. DQP Queries, DQP Delinquent Forms, 
DQP Form Status and the DQP Reports modules are available to access details and reports of unanswered queries, 
delinquent forms, forms with current status and timeliness reports. Review the DQP modules on a regular basis to 
manage specified queries and delinquent forms. 
The DQP is accessible by site staff who are rostered to a site and have access to the CTSU website. Staff who have 
Rave study access can access the Rave study via a direct link available in the DQP modules. 
CTSU Delinquency Notification emails are sent to primary contacts at sites twice a month. These notifications serve as 
alerts that queries and/or delinquent forms require site review, providing a summary count of queries and delinquent forms 
for each Rave study that a site is participating in. Additional site staff can subscribe and unsubscribe to these notifications 
using the CTSU Report and Information Subscription Portal on the CTSU members’ website. 
To learn more about DQP use and access, click on the Help Topics button displayed on the Rave Home, DQP 
Queries, DQP Delinquent Forms, DQP Form Status, and DQP Reports modules. 
 Central Monitoring (CM) Review is required for this protocol. CM allows Lead Protocol Organizations (LPOs) to remotely 
compare data entered in Rave to source documentation to ensure that sites are adhering to the protocol and central 
monitoring plan as well as accurately transcribing data from patients’ charts (i.e., source data verification).  
Sites can upload source documents required for CM Review as documented in the central monitoring plan using the Source 
Document Portal (SDP) application. This application is also available on the CTSU members’ website under Auditing & 
Monitoring and may also be accessed using a direct link within Rave on the CM Alert form. Site staff with any of the Rave 
roles on a relevant site roster can view and upload source documents. Prior to saving source documents on the SDP, each 
site is responsible for removing or redacting any Personally Identifiable Information (PII) (note that functionality to do this 
redaction exists within the SDP itself). Designated LPO staff will review each document after it has been loaded on the SDP 
to ensure the appropriate documents have been uploaded and to ensure PII is redacted. 
Additional information on the SDP is available on the CTSU SDP application under Browser > Document Repository in 
the Help Topics button or by contacting the CTSU Help Desk (1-888-823-5923 or ctsucontact@westat.com).   
 
13.2.2 Rave-CTEP AERS Integration 
 
The CTEP Adverse Event Reporting System (CTEP-AERS) integration enables evaluation of AEs entered in Rave to 
determine whether they require expedited reporting and facilitates entry in CTEP-AERS for those AEs requiring expedited 
reporting. Sites must initiate all AEs for this study in Medidata Rave.    
 
Treatment-emergent AEs: All AEs that occur after start of treatment are collected in Medidata Rave using the AE CRF, 
which is available for entry at each treatment course or reporting period and is used to collect AEs that start during the 
period or persist from the previous reporting period. AEs that occur 30 days after the last administration of the 
Investigational Agent/Intervention are collected using the Late Adverse Event form.  
 
Prior to sending AEs through the rule evaluation process, site staff should verify the following on the AE CRF in Rave: 
• 
The reporting period (course/cycle) is correct; and 
• 
AEs are recorded and complete (no missing fields) and the form is query free. Note: Fields added to the form during 
study build do not need to be query free for the integration call with CTEP-AERS to be a success. 
 
The CRA reports AEs in Rave at the time the Site Investigator learns of the event. If the CRA modifies an AE, it must be 

                              
 
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re-submitted for rules evaluation. 
 
Upon completion of AE entry in Medidata Rave, the CRA submits the AE for rules evaluation by completing the Expedited 
Reporting Evaluation Form (i.e., checking the box Send All AEs for Evaluation and save the form). Both NCI and protocol-
specific reporting rules evaluate the AEs submitted for expedited reporting. A report is initiated in CTEP-AERS using 
information entered in Medidata Rave for AEs that meet reporting requirements. The CRA completes the report by accessing 
CTEP-AERS via a direct link on the Medidata Rave Expedited Reporting Evaluation Form. Contact the CTSU Help Desk 
at 1-888-823-5923 or by email at ctsucontact@westat.com if you have any issues submitting an expedited report in CTEP-
AERS. 
 
In the rare occurrence that Internet connectivity is lost, a 24-hour notification is to be made to CTEP by telephone at 301-
897-7497. Once Internet connectivity is restored, the 24-hour notification that was phoned in must be entered immediately 
into CTEP-AERS using the deep link from Medidata Rave. 
 
Additional information about the CTEP-AERS integration is available on the CTSU member’s website: 
• 
Study specific documents: Protocols > Documents   
• 
Protocol Related Documents > Adverse Event Reporting; and  
• 
Additional resources: Resources > CTSU Operations Information> User Guides & Help Topics. 
 
NCI requirements for SAE reporting are available on the CTEP website:  
• 
“NCI 
Guidelines 
for 
Investigators: 
Adverse 
Event 
Reporting 
Requirements” 
is 
available 
at 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguidelines.pdf. 
 
13.2.3 Monitoring 
 
On-site, retrospective source data verification is completed by Theradex on an annual basis for 100% of COG PEP-
CTN patients enrolled in early phase clinical trials. 
 
This study will additionally include central monitoring as part of data review. Source documents will be uploaded 
via CTSU’s Central Monitoring Portal. (See Appendix W for details.)  
 
13.2.4 Categories of Research Records  
Research records for this study can be divided into three categories: 
 
1. Non-computerized Information: Therapy Delivery Maps (TDMs), Pathology Reports, Surgical 
Reports. These forms are uploaded into RAVE. 
 
2. Reference Labs, Biopathology Reviews, and Imaging Center data: These data accompany submissions 
to these centers, which forward their data electronically to the PEP-CTN Operations and Data/Statistics 
Center. 
 
3. Computerized Information Electronically Submitted: All other data will be entered in RAVE with the 
aid of schedules and worksheets (essentially paper copies of the OPEN and RAVE screens) provided 
in the case report form (CRF) packet. 
 
See separate CRF Packet, which includes submission schedule. 
13.3 
CTEP Multicenter Guidelines 
 

                              
 
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This protocol will adhere to the policies and requirements of the CTEP Multicenter Guidelines.  The specific responsibilities 
of the Principal Investigator and the Coordinating Center (Study Coordinator) and the procedures for auditing are presented 
in Appendix C. 
• 
The Principal Investigator/Coordinating Center is responsible for distributing all IND Action Letters or Safety 
Reports received from CTEP to all participating institutions for submission to their individual IRBs for action as 
required. 
 
• 
Except in very unusual circumstances, each participating institution will order DCTD-supplied agents directly from 
CTEP.  Agents may be ordered by a participating site only after the initial IRB approval for the site has been 
forwarded by the Coordinating Center to the CTEP PIO (PIO@ctep.nci.nih.gov) except for Group studies. 
 
 
13.4 
CRADA/CTA/CSA 
 
The agent(s) supplied by CTEP, DCTD, NCI used in this protocol is/are provided to the NCI under a Collaborative 
Agreement (CRADA, CTA, CSA) between the Pharmaceutical Company(ies) (hereinafter referred to as “Collaborator(s)”) 
and the NCI Division of Cancer Treatment and Diagnosis.  Therefore, the following obligations/guidelines, in addition to 
the provisions in the “Intellectual Property Option to Collaborator”  
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm) contained within the terms of award, apply to the 
use of the Agent(s) in this study: 
 
1. Agent(s) may not be used for any purpose outside the scope of this protocol, nor can Agent(s) be transferred or licensed 
to any party not participating in the clinical study.  Collaborator(s) data for Agent(s) are confidential and proprietary to 
Collaborator(s) and shall be maintained as such by the investigators.  The protocol documents for studies utilizing 
Agents contain confidential information and should not be shared or distributed without the permission of the NCI.  If 
a copy of this protocol is requested by a patient or patient’s family member participating on the study, the individual 
should sign a confidentiality agreement.  A suitable model agreement can be downloaded from: http://ctep.cancer.gov. 
 
2. For a clinical protocol where there is an investigational Agent used in combination with (an)other Agent(s), each the 
subject of different Collaborative Agreements, the access to and use of data by each Collaborator shall be as follows 
(data pertaining to such combination use shall hereinafter be referred to as "Multi-Party Data”): 
 
a. NCI will provide all Collaborators with prior written notice regarding the existence and nature of any agreements 
governing their collaboration with NCI, the design of the proposed combination protocol, and the existence of any 
obligations that would tend to restrict NCI's participation in the proposed combination protocol. 
 
b. Each Collaborator shall agree to permit use of the Multi-Party Data from the clinical trial by any other Collaborator 
solely to the extent necessary to allow said other Collaborator to develop, obtain regulatory approval or 
commercialize its own Agent. 
 
c. Any Collaborator having the right to use the Multi-Party Data from these trials must agree in writing prior to the 
commencement of the trials that it will use the Multi-Party Data solely for development, regulatory approval, and 
commercialization of its own Agent. 
 
3. Clinical Trial Data and Results and Raw Data developed under a Collaborative Agreement will be made available to 
Collaborator(s), the NCI, and the FDA, as appropriate and unless additional disclosure is required by law or court order 
as 
described 
in 
the 
IP 
Option 
to 
Collaborator 
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm).  Additionally, all Clinical Data and Results 

                              
 
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and Raw Data will be collected, used and disclosed consistent with all applicable federal statutes and regulations for the 
protection of human subjects, including, if applicable, the Standards for Privacy of Individually Identifiable Health 
Information set forth in 45 C.F.R. Part 164. 
 
4. When a Collaborator wishes to initiate a data request, the request should first be sent to the NCI, who will then notify 
the appropriate investigators (Group Chair for Cooperative Group studies, or PI for other studies) of Collaborator's wish 
to contact them. 
 
5. Any data provided to Collaborator(s) for Phase 3 studies must be in accordance with the guidelines and policies of the 
responsible Data Monitoring Committee (DMC), if there is a DMC for this clinical trial. 
 
6. Any manuscripts reporting the results of this clinical trial must be provided to CTEP by the Group office for Cooperative 
Group studies or by the principal investigator for non-Cooperative Group studies for immediate delivery to 
Collaborator(s) for advisory review and comment prior to submission for publication.  Collaborator(s) will have 30 days 
from the date of receipt for review. Collaborator shall have the right to request that publication be delayed for up to an 
additional 30 days in order to ensure that Collaborator’s confidential and proprietary data, in addition to 
Collaborator(s)’s intellectual property rights, are protected.  Copies of abstracts must be provided to CTEP for 
forwarding to Collaborator(s) for courtesy review as soon as possible and preferably at least three days prior to 
submission, but in any case, prior to presentation at the meeting or publication in the proceedings. Press releases and 
other media presentations must also be forwarded to CTEP prior to release. Copies of any manuscript, abstract and/or 
press release/ media presentation should be sent to: 
 
Email:  ncicteppubs@mail.nih.gov 
 
The Regulatory Affairs Branch will then distribute them to Collaborator(s). No publication, manuscript or other form of 
public disclosure shall contain any of Collaborator’s confidential/ proprietary information. 
 
 
 

                              
 
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14 REFERENCES 
 
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Brahmer, J. R., Lacchetti, C., Schneider, B. J., Atkins, M. B., Brassil, K. J., Caterino, J. M., . . . Ginex, P. (2018). 
Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American 
Society of Clinical Oncology Clinical Practice Guideline. Journal of clinical oncology: official journal of the American 
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Burchill, S. A., Beiske, K., Shimada, H., Ambros, P. F., Seeger, R., Tytgat, G. A., . . . Berthold, F. (2017). Recommendations 
for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the 
International Neuroblastoma Response Criteria Bone Marrow Working Group. Cancer, 123(7), 1095-1105.  
 
Ceschel, S., Casotto, V., Valsecchi, M. G., Tamaro, P., Jankovic, M., Hanau, G., . . . Cuttini, M. (2006). Survival after 
relapse in children with solid tumors: a follow-up study from the Italian off-therapy registry. Pediatr Blood Cancer, 47(5), 
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Chan, K. S., Espinosa, I., Chao, M., Wong, D., Ailles, L., Diehn, M., . . . Weissman, I. L. (2009). Identification, molecular 
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U S A, 106(33), 14016-14021. doi:10.1073/pnas.0906549106 
 
Chao, M. P., Alizadeh, A. A., Tang, C., Myklebust, J. H., Varghese, B., Gill, S., . . . Majeti, R. (2010). Anti-CD47 antibody 
synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell, 142(5), 699-713. 
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Chao, M. P., Jaiswal, S., Weissman-Tsukamoto, R., Alizadeh, A. A., Gentles, A. J., Volkmer, J., . . . Weissman, I. L. (2010). 
Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl 
Med, 2(63), 63ra94. doi:10.1126/scitranslmed.3001375 
 
Chao, M. P., Majeti, R., & Weissman, I. L. (2011). Programmed cell removal: a new obstacle in the road to developing 
cancer. Nat Rev Cancer, 12(1), 58-67. doi:10.1038/nrc3171 
 
Davis, K. L., Fox, E., Merchant, M. S., Reid, J. M., Kudgus, R. A., Liu, X., . . . Mackall, C. L. (2020). Nivolumab in children 
and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-
arm, phase 1-2 trial. Lancet Oncol, 21(4), 541-550. doi:10.1016/S1470-2045(20)30023-1 
 
Davis, R. J., Moore, E. C., Clavijo, P. E., Friedman, J., Cash, H., Chen, Z., . . . Allen, C. (2017). Anti-PD-L1 efficacy can 
be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kdelta/gamma. Cancer Res, 
77(10), 2607-2619. doi:10.1158/0008-5472.CAN-16-2534 
 
Dobrenkov, K., Ostrovnaya, I., Gu, J., Cheung, I. Y., & Cheung, N. K. (2016). Oncotargets GD2 and GD3 are highly 
expressed in sarcomas of children, adolescents, and young adults. Pediatr Blood Cancer, 63(10), 1780-1785. 
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Edris, B., Weiskopf, K., Volkmer, A. K., Volkmer, J. P., Willingham, S. B., Contreras-Trujillo, H., . . . van de Rijn, M. 
(2012). Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic leiomyosarcoma. Proc 
Natl Acad Sci U S A, 109(17), 6656-6661. doi:10.1073/pnas.1121629109 
 

                              
 
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Erbe, A. K., Wang, W., Carmichael, L., Kim, K., Mendonça, E. A., Song, Y., . . . Sondel, P. M. (2018). Neuroblastoma 
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Feng, M., Chen, J. Y., Weissman-Tsukamoto, R., Volkmer, J. P., Ho, P. Y., McKenna, K. M., . . . Weissman, I. L. (2015). 
Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. Proc Natl Acad Sci U S A, 
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Frost, J. D., Hank, J. A., Reaman, G. H., Frierdich, S., Seeger, R. C., Gan, J., . . . Sondel, P. M. (1997). A phase I/IB trial of 
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Gubin, M. M., Artyomov, M. N., Mardis, E. R., & Schreiber, R. D. (2015). Tumor neoantigens: building a framework for 
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Huang, Y., Ma, Y., Gao, P., & Yao, Z. (2017). Targeting CD47: the achievements and concerns of current studies on cancer 
immunotherapy. J Thorac Dis, 9(2), E168-E174. doi:10.21037/jtd.2017.02.30 
 
Jaiswal, S., Jamieson, C. H., Pang, W. W., Park, C. Y., Chao, M. P., Majeti, R., . . . Weissman, I. L. (2009). CD47 is 
upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell, 138(2), 271-285. 
doi:10.1016/j.cell.2009.05.046 
 
Keyel, M. E., & Reynolds, C. P. (2018). Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development 
and place in therapy. Biologics : targets & therapy, 13, 1-12. doi:10.2147/BTT.S114530 
Krampitz, G. W., George, B. M., Willingham, S. B., Volkmer, J. P., Weiskopf, K., Jahchan, N., . . . Weissman, I. L. (2016). 
Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors. Proc Natl Acad Sci U S A, 
113(16), 4464-4469. doi:10.1073/pnas.1600007113 
 
Lagmay, J. P., Krailo, M. D., Dang, H., Kim, A., Hawkins, D. S., Beaty, O., 3rd, . . . Janeway, K. A. (2016). Outcome of 
patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, Pediatric Oncology 
Group, and Children's Oncology Group: Learning from the past to move forward. J Clin Oncol, 34(25), 3031-3038. 
doi:10.1200/JCO.2015.65.5381 
 
Liu, J., Wang, L., Zhao, F., Tseng, S., Narayanan, C., Shura, L., . . . Majeti, R. (2015). Pre-clinical development of a 
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antibody 
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therapeutic 
potential. 
PloS 
one, 
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e0137345. 
doi:10.1371/journal.pone.0137345 
 
Liu, X., Kwon, H., Li, Z., & Fu, Y. X. (2017). Is CD47 an innate immune checkpoint for tumor evasion? J Hematol Oncol, 
10(1), 12. doi:10.1186/s13045-016-0381-z 
 
Liu, X., Pu, Y., Cron, K., Deng, L., Kline, J., Frazier, W. A., . . . Xu, M. M. (2015). CD47 blockade triggers T cell-mediated 
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Sikic, B. I., Lakhani, N., Patnaik, A., Shah, S. A., Chandana, S. R., Rasco, D., . . . Padda, S. K. (2019). First-in-human, first-
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(2013). Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell 
response. Proc Natl Acad Sci U S A, 110(27), 11103-11108. doi:10.1073/pnas.1305569110 
 
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doi:10.1172/JCI81603 
 
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APPENDIX A: PERFORMANCE STATUS CRITERIA 
 
Performance 
Status % 
Karnofsky Scale  
 (Age >16 years) 
Lansky Scale 
 (Age: <16 years) 
ECOG (Zubrod) 
100 
Normal, no complaints, no evidence of 
disease 
Fully active 
0 
Fully Active, able to carry on all pre-
disease 
performance 
without 
restrictions. 
90 
Able to carry on normal activity 
Minor restriction in physically strenuous 
play 
80 
Normal activity with effort 
Restricted in strenuous play, tires more 
easily, otherwise active 
1 
Restricted in physically strenuous 
activity but ambulatory, able to carry 
out light or sedentary work, e.g. light 
housework, office work. 
70 
Cares for self, unable to carry on normal 
activity or to do active work 
Both greater restrictions of, and less time 
spent in active play 
60 
Requires occasional assistance but is able 
to care for most needs 
Ambulatory up to 50% of time, limited 
active play with assistance/supervision 
2 
Ambulatory and capable of all self-care 
but unable to carry out any work 
activities. Up and about more than 50% 
of waking hours. 
50 
Requires considerable assistance and 
frequent medical care 
Considerable assistance required for any 
active play, fully able to engage in quiet play 
40 
Disabled, requires special care and 
assistance 
 Able to initiate quite activities 
3 
Capable of only limited self-care, 
confined to bed or chair more than 50% 
of waking hours. 
30 
Severely 
disabled, 
hospitalization 
indicated, although death not imminent 
Needs considerable assistance for quiet 
activity 
20 
Very sick, hospitalization necessary 
Limited to very passive activity initiated by 
others (e.g., TV) 
4 
Completely disabled. Cannot carry out 
any self-care. Totally confined to a bed 
or chair. 
10 
Moribund, fatal process progressing 
rapidly 
Completely disabled, not even passive play 
 
 

                              
 
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APPENDIX B: FORMULA TO ESTIMATE RENAL FUNCTION USING SERUM CREATININE 
 
Formulas to estimate renal function using serum creatinine provided by the NCI’s Investigational Drug 
Steering Committee (IDSC) Pharmacological Task Force in table below. 
 
1. Estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) (Levey et al., 2009). 
 
Formulae: 
 
Race and 
Sex 
Serum Creatinine (SCr), 
µmol/L (mg/dL) 
Equation 
Black 
 
 
Female 
≤62 (≤0.7) 
GFR = 166 × (SCr/0.7)−0.329 × (0.993)Age 
 
>62 (>0.7) 
GFR = 166 × (SCr/0.7)−1.209 × (0.993)Age 
Male 
≤80 (≤0.9) 
GFR = 163 × (SCr/0.9)−0.411 × (0.993)Age 
 
>80 (>0.9) 
GFR = 163 × (SCr/0.9)−1.209 × (0.993)Age 
 
 
 
White or 
other 
 
 
Female 
≤62 (≤0.7) 
GFR = 144 × (SCr/0.7)−0.329 × (0.993)Age 
 
>62 (>0.7) 
GFR = 144 × (SCr/0.7)−1.209 × (0.993)Age 
Male 
≤80 (≤0.9) 
GFR = 141 × (SCr/0.9)−0.411 × (0.993)Age 
 
>80 (>0.9) 
GFR = 141 × (SCr/0.9)−1.209 × (0.993)Age 
 
SCr in mg/dL; Output is in mL/min/1.73 m2 and needs no further conversions. 
 
2. eGFR using the Modification of Diet in Renal Disease (MDRD) Study (Levey et al., 2006). 
 
175 x SCr–1.154 × age–0.203 × 0.742 (if female) × 1.212 (if black) 
Output is in mL/min/1.73 m2 and needs no further conversions. 
3. Estimated creatinine clearance (ClCr) by the Cockcroft-Gault (C-G) equation (Cockcroft and 
Gault, 1976). 
 
 
Followed by conversion to a value normalized to 1.73 m2 with the patient’s body surface area 
(BSA). 
 
References 
1. Levey, A.S., L.A. Stevens, C.H. Schmid, et al.  (2009).  A new equation to estimate glomerular filtration 
rate.  Ann Inter Med.  150:604-612. 
2. Levey, A.S., J. Coresh, T. Greene, et al.  (2006).  Using standardized serum creatinine values in the 
modification of diet in renal disease study equation for estimating glomerular filtration rate.  Ann Intern 
Med.  145:247-254. 
3. Cockcroft, D.W. and M.H. Gault.  (1976).  Prediction of creatinine clearance from serum creatinine.  
Nephron.  16:31-41. 
 

                              
 
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APPENDIX C: CTEP MULTICENTER GUIDELINES 
 
If an institution wishes to collaborate with other participating institutions in performing a CTEP-sponsored research 
protocol, then the guidelines below must be followed. 
 
Responsibility of the Protocol Chair  
• 
The Protocol Chair will be the single liaison with the CTEP Protocol and Information Office (PIO).  The 
Protocol Chair is responsible for the coordination, development, submission, and approval of the protocol as 
well as its subsequent amendments.  The protocol must not be rewritten or modified by anyone other than the 
Protocol Chair.  There will be only one version of the protocol, and each participating institution will use that 
document.  The Protocol Chair is responsible for assuring that all participating institutions are using the correct 
version of the protocol. 
• 
The Protocol Chair is responsible for the overall conduct of the study at all participating institutions and for 
monitoring its progress.  All reporting requirements to CTEP are the responsibility of the Protocol Chair.  
• 
The Protocol Chair is responsible for the timely review of Adverse Events (AE) to assure safety of the patients. 
• 
The Protocol Chair will be responsible for the review of and timely submission of data for study analysis. 
 
Responsibilities of the Coordinating Center 
• 
Each participating institution will have an appropriate assurance on file with the Office for Human Research 
Protection (OHRP), NIH.  The Coordinating Center is responsible for assuring that each participating 
institution has an OHRP assurance and must maintain copies of IRB approvals from each participating site.  
• 
Prior to the activation of the protocol at each participating institution, an OHRP form 310 (documentation of 
IRB approval) must be submitted to the CTEP PIO. 
• 
The Coordinating Center is responsible for central patient registration.  The Coordinating Center is responsible 
for assuring that IRB approval has been obtained at each participating site prior to the first patient registration 
from that site. 
• 
The Coordinating Center is responsible for the preparation of all submitted data for review by the Protocol 
Chair. 
• 
The Coordinating Center will maintain documentation of AE reports.  There are two options for AE reporting: 
(1) participating institutions may report directly to CTEP with a copy to the Coordinating Center, or (2) 
participating institutions report to the Coordinating Center who in turn report to CTEP.  The Coordinating 
Center will submit AE reports to the Protocol Chair for timely review. 
• 
Audits may be accomplished in one of two ways:  (1) source documents and research records for selected 
patients are brought from participating sites to the Coordinating Center for audit, or (2) selected patient records 
may be audited on-site at participating sites.  If the NCI chooses to have an audit at the Coordinating Center, 
then the Coordinating Center is responsible for having all source documents, research records, all IRB 
approval documents, NCI Drug Accountability Record forms, patient registration lists, response assessments 
scans, x-rays, etc., available for the audit. 
 
Inclusion of Multicenter Guidelines in the Protocol 
• 
The protocol must include the following minimum information:  
➢ The title page must include the name and address of each participating institution and the name, telephone 
number and e-mail address of the responsible investigator at each participating institution. 
➢ The Coordinating Center must be designated on the title page. 
➢ Central registration of patients is required.  The procedures for registration must be stated in the protocol. 
➢ Data collection forms should be of a common format.  Sample forms should be submitted with the 
protocol.  The frequency and timing of data submission forms to the Coordinating Center should be stated. 

                              
 
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➢ Describe how AEs will be reported from the participating institutions, either directly to CTEP or through 
the Coordinating Center. 
➢ Describe how Safety Reports and Action Letters from CTEP will be distributed to participating 
institutions. 
 
Agent Ordering 
• 
Except in very unusual circumstances, each participating institution will order DCTD-supplied investigational 
agents directly from CTEP.  Investigational agents may be ordered by a participating site only after the initial 
IRB approval for the site has been forwarded by the Coordinating Center to the CTEP PIO.  

                              
 
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APPENDIX D: PRE-BIOPSY ASSESSMENT 
 
A pre-biopsy lesion assessment can increase trial safety and efficiency. By agreement between all investigators, an attempt 
at biopsy will be made if the clinical trial team determines that a biopsy poses minimal relative risk, provides potential 
clinical gain to the participant, and will likely yield sufficient tissue for analysis.   
 
Pre-biopsy assessments will be reported and tracked through a trial-specific CRF within the CTEP Medidata Rave system. 
Additional information can be found in the Investigational Radiology SOP available at:   
https://ctep.cancer.gov/initiativesPrograms/docs/ETCTN_IR_Research_Biopsy_SOP.pdf.  
 
Individual Patient Pre-Biopsy Assessment  
IR co-investigators are encouraged to apply this pre-biopsy scoring and correlation system to assist in the determination of 
biopsy appropriateness. 
 
IR co-investigators assign a subjective score of 1-3 based on likelihood of success due to lesion characteristics.  
 
1.  Biopsy should not be done  
a) Due to safety concerns 
b) Due to lack of suitable lesion for biopsy 
 
2.  Uncertainty about success  
a) Due to access path to lesion 
b) Due to lesion characteristics  
 
3.  Likely successful  
• 
Lesion characteristics to be considered 
• 
Size (small) (<2 cm) 
• 
Location/path to lesion 
• 
Morphologic features (necrosis, sub-solid, sclerosis, ill-defined/infiltrative) 
• 
PET (+/-), avidity  
• 
Organ/site (sclerotic bone is low yield; fine needle aspiration to be used) 
 
 
 
 
 

                              
 
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APPENDIX E: PATIENT CLINICAL TRIAL WALLET CARD 
 
 
 
 
CLINICAL TRIAL WALLET CARD 
Show this card to all of your healthcare 
providers and keep it with you in case you 
go to the emergency room. 
Patient Name:        
Diagnosis:        
Study Doctor:       
Study Doctor Phone #:       
NCI Trial #:        
Study Drug(S):        
 
 
 
 
For more information: 1-800-4-CANCER 
 
 
 
 

                              
 
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APPENDIX F: YOUTH INFORMATION SHEETS 
 
INFORMATION SHEET REGARDING RESEARCH STUDY PED-CITN-03 
(for children from 7 through 13 years of age) 
We want to tell you all about this study. You and your family can decide if you want to be in it. Ask questions if 
you don’t understand. 
 
 
1. What is the name of the study? Testing the combination of two immunotherapy drugs (magrolimab and 
dinutuximab) in children, adolescents, and young adults with relapsed/refractory neuroblastoma or relapsed 
osteosarcoma 
 
2. Who is in charge of the study? The study is being done by PEP-CTN and is being done at other hospitals. 
 
3. What is this study about? We are asking you to take part in a research study because you have osteosarcoma or 
neuroblastoma that has come back or has not gotten better with other treatments. Osteosarcoma is a type of bone 
cancer. Neuroblastoma is a type of cancer that grows in several areas of the body, including the abdomen and in the 
chest, neck, and near the spine. After doing tests, we have found that you have one of these types of cancer. A 
research study is when doctors work together to try out new ways to help people who are sick. We will still take 
care of you no matter what you decide.   
 
This study is testing two immune drugs called Hu5F9-G4 (or magrolimab) and dinutuximab in people with cancer 
like you. Doctors want to see what effects (both good and bad) these drugs have on people and their cancer.   
 
4. What will happen to me in this study? Children who are part of this study will go to the study doctor’s office every 
week for about 8-9 weeks and then every other week, to be given the magrolimab. Every 3 weeks, starting with 
Cycle 1, you will stay in the hospital for about 4 days and be given the dinutuximab. You will get the research drugs 
for about 9 months if they make your cancer better or if your cancer does not get worse.You will have some tests 
and check-ups done more often than if you weren’t part of this study. Some of these tests will require extra needle 
sticks for blood collection. We will follow your health after you finish the study treatment. 
 
The following would be done at the study visits:  
 
• 
You will be asked questions about your health and look at your past doctor visits and use information about 
your care. 
 
• 
We will take some blood by putting a needle in your arm. This blood will be used for research tests and to 
monitor your safety and health. The blood will be taken when you first join the study, while you are taking the 
research drugs, and when you stop taking the research drugs.  
 
• 
We will check your temperature, breathing, and heartbeat at most visits.   
 
• 
A doctor or a nurse will give you the research drugs with a needle in your arm. 
 
• 
Scans or exams of your body will be done to learn more about your cancer.  
 
 

                              
 
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• 
When you first join this study, we will do research tests on a piece of your cancer. This piece may be left over 
from a test or surgery you already had for your cancer care or a new piece from a test or surgery if you have 
this before you start taking the research drugs. 
 
If you have a test or surgery for your cancer care after you start taking the research drugs, we will take a piece of 
your cancer from this procedure and do research tests on it as well. The tests on your cancer pieces and bone marrow 
are to learn how magrolimab and dinutuximab can be used to help other children with cancer like you. You and 
your study doctor will not receive the results of these tests.  
 
Sometimes good things can happen to people when they are in a research study. These good things are called 
“benefits”.We hope that a benefit to you of being part of this study is a better chance at getting rid of your 
neuroblastoma or osteosarcoma, but we don’t know for sure if there is any benefit of being part of this study. 
 
 
Sometimes bad things can happen to people when they are in a research study. These bad things are called “risks”. 
The risks to you from this study are: 
 
• 
The needle that we use to take your blood may hurt. Sometimes the needle can leave a bruise on the skin.  We 
can put a cream on your skin before we take blood. This cream will numb your skin so the needle won’t hurt as 
much. If you have a catheter (plastic tube) put in a large vein, your blood may be taken through this catheter, 
so we won’t have to put in a needle to take your blood. This catheter may also be used to give you medicines. 
 
• 
The study drugs can make you feel hot or cold, sick to your stomach, head hurt, and more tired than usual. You 
could also get a rash or cough.  
 
• 
The study drugs can make you feel strange or different. You must tell your parents and the study doctor if you 
feel sick when taking the study drugs. 
 
• 
You may not be able to go to school or play or take part in activities for a little while. 
 
• 
Other things may happen to you that we don’t yet know about. You can say ‘no’ to what we ask you to do for 
the research at any time and we will stop.   
 
5. Do I have to be in the study? Your family can choose to be part of this study or not. You and your family can also 
decide to stop being in this study at any time once you start. The doctors and nurses will still take care of you. There 
may be other treatments for your illness that your doctor can tell you about.  Make sure to ask your doctors any 
questions that you have. 
 
6. We are asking your permission to collect additional tumor tissue, bone marrow, and blood samples. We want to see 
if there are ways to tell how the cancer will respond to treatment. The tumor tissue and bone marrow samples will 
be taken at the same time as for your other procedures, so there would be no extra procedures. The blood samples 
will be taken at the same times that blood is collected for your other procedures so there will be no extra needle 
sticks. You can still take part in this study even if you don't allow us to collect extra tumor tissue, bone marrow, or 
blood samples for research.  
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 129 
 
 
INFORMATION SHEET REGARDING RESEARCH STUDY PED-CITN-03 
(for teens from 14 through 17 years of age) 
We want to tell you all about this study. You and your family can decide if you want to be in it. Ask questions if 
you don’t understand. 
 
1. What is the name of the study?  Testing the combination of two immunotherapy drugs (magrolimab and 
dinutuximab) in children, adolescent, and young adults with relapsed/refractory neuroblastoma or relapsed 
osteosarcoma 
 
2. Who is in charge of the study? The study is being done by PEP-CTN and is being done at other hospitals. 
 
3. What is this study about? We are asking you to take part in a research study because you have osteosarcoma or 
neuroblastoma that has come back or has not gotten better with other treatments. Osteosarcoma is a type of bone 
cancer. Neuroblastoma is a type of cancer that grows in several areas of the body, including the abdomen and in the 
chest, neck, and near the spine. After doing tests, we have found that you have one of these types of cancer. A 
research study is when doctors work together to try out new ways to help people who are sick. We will still take 
care of you no matter what you decide.   
 
This study is testing two immune drugs called Hu5F9-G4 (or magrolimab) and dinutuximab in people with cancer 
like you. Doctors want to see what effects (both good and bad) these drugs have on people and their cancer.   
 
4. What will happen to me in this study? Children who are part of this study will go to the study doctor’s office every 
week for about 8-9 weeks and then every other week, to be given the magrolimab. Every 3 weeks, starting with 
Cycle 1, you will stay in the hospital for about 4 days and be given the dinutuximab. You will get the research drugs 
for about 9 months if they make your cancer better or if your cancer does not get worse. You will have some tests 
and check-ups done more often than if you weren’t part of this study. Some of these tests will require extra needle 
sticks for blood collection. We will follow your health after you finish the study treatment. 
 
The following would be done at the study visits:  
 
• 
You will be asked questions about your health and look at your past doctor visits and use information about 
your care. 
 
• 
We will take some blood by putting a needle in your arm. This blood will be used for research tests and to 
monitor your safety and health. The blood will be taken when you first join the study, while you are taking the 
research drugs, and when you stop taking the research drugs.  
 
• 
We will check your temperature, breathing, and heartbeat at most visits.   
 
• 
A doctor or a nurse will give you the research drugs with a needle in your arm. 
 
• 
Scans or exams of your body will be done to learn more about your cancer. 
 
 
• 
When you first join this study, we will do research tests on a piece of your cancer. This piece may be left over 
from a test or surgery you already had for your cancer care or a new piece from a test or surgery if you have 
this before you start taking the research drugs. 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 130 
 
 
If you have a test or surgery for your cancer care after you start taking the research drugs, we will take a piece of 
your cancer from this procedure and do research tests on it as well. The tests on your cancer pieces and bone marrow 
are to learn how magrolimab and dinutuximab can be used to help other children with cancer like you. You and 
your study doctor will not receive the results of these tests.  
 
Sometimes good things can happen to people when they are in a research study. These good things are called 
“benefits”. We hope that a benefit to you of being part of this study is a better chance at getting rid of your 
neuroblastoma or osteosarcoma, but we don’t know for sure if there is any benefit of being part of this study. 
 
 
Sometimes bad things can happen to people when they are in a research study. These bad things are called “risks”. 
The risks to you from this study are: 
 
• 
The needle that we use to take your blood may hurt. Sometimes the needle can leave a bruise on the skin.  We 
can put a cream on your skin before we take blood. This cream will numb your skin so the needle won’t hurt as 
much. If you have a catheter (plastic tube) put in a large vein, your blood may be taken through this catheter, 
so we won’t have to put in a needle to take your blood. This catheter may also be used to give you medicines. 
 
• 
The study drugs can make you feel hot or cold, sick to your stomach, head hurt, and more tired than usual. You 
could also get a rash or cough.  
 
• 
The study drugs can make you feel strange or different. You must tell your parents and the study doctor if you 
feel sick when taking the study drugs. 
 
• 
You may not be able to go to school or play or take part in activities for a little while. 
 
• 
Other things may happen to you that we don’t yet know about. You can say ‘no’ to what we ask you to do for 
the research at any time and we will stop.   
 
5. Will I be paid to be in this study? You will not be paid for being in this study. 
 
 
6.  Do I have to be in the study? You and your family can choose to be part of this study or not. You and your family 
can also decide to stop being in this study at any time once you start. The doctors and nurses will still take care of 
you.There may be other treatments for your illness that your doctor can tell you about.  Make sure to ask your 
doctors any questions that you have.  
 
7. We are asking your permission to collect additional tumor tissue, bone marrow, and blood samples. We want to 
see if there are ways to tell how the cancer will respond to treatment. The tumor tissue and bone marrow samples 
will be taken at the same time as for your other procedures, so there would be no extra procedures. The blood 
samples will be taken at the same times that blood is collected for your other procedures so there will be no extra 
needle sticks. You can still take part in this study even if you don't allow us to collect extra tumor tissue, bone 
marrow, or blood samples for research.  
 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 131 
 
 
APPENDIX G: PHARMACOKINETIC WORKSHEET FOR MAGROLIMAB, ARM A 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Serum samples for PK analysis should be obtained according to instructions in Section 5.0 
 
Record the exact date and time the sample is drawn 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
1 
Priming (Safety 
Lead-In), Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Priming 
(Safety Lead-
In), Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
 
Infusion Stop Time: |__|__| : |__|__| 
 
  
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
 2 
Safety Lead-In, 
Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Safety Lead-In, 
Day 8  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
 
Infusion Stop 
Time: |__|__| 
: |__|__| 
 
Dose on  
Safety Lead-In, Day 
1  
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
3 
Safety Lead-In, 
Day 15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Safety Lead-In, 
Day 15  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 132 
 
 
4 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
5 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day 8  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
6 
Cycle 1, Day 15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day 
15  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
7 
Cycle 2, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 2, Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
8 
Cycle 3, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 3, Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 133 
 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
9 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 5, Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
10 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 7, Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
11 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 9, Day 1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
12 
Cycle 11, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 11, Day 
1  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample Collected 
(24-hr clock) 
13 
End of Therapy 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Last dose given  
 
Date:___/___/___ 
 
Infusion Start Time: |__|__| : 
 
Infusion Stop Time: |__|__| : |__|__| 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 134 
 
 
|__|__| 
 
One copy of this Pharmacokinetic Form should be uploaded into RAVE. A second copy should be sent with the samples to the address 
listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 135 
 
 
APPENDIX H: PHARMACOKINETIC WORKSHEET FOR MAGROLIMAB, ARM B 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Serum samples for PK analysis should be obtained according to instructions in Section 5.0.  
 
Record the exact date and time the sample is drawn  
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
1 
Priming, Day 1 
Prior to Hu5F9-G4 
(magrolimab) infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Priming, Day 1 
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
2 
Cycle 1, Day 1 
Prior to Hu5F9-G4 
(magrolimab) infusion 
___/___/___ 
|__|__| : |__|__| 
Dose on  
Cycle 1, Day 1   
Date:___/___/
___ 
Infusion Start Time: |__|__| : 
|__|__| 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
3 
Cycle 1, Day 8 
Prior to Hu5F9-G4 
(magrolimab) infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day 8  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
4 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 
(magrolimab) infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day  
15   
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 136 
 
 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
5 
Cycle 1, Day 
22 
Prior to Hu5F9-G4 
(magrolimab) infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day  
22   
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
6 
Cycle 2, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 2, Day 1  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
7 
Cycle 3, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 3, Day 1  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
8 
Cycle 5, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 5, Day 1  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 137 
 
 
9 
Cycle 7, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 7, Day 1  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
10 
Cycle 9, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 9, Day 1  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
11 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 11, Day 
1  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time Sample 
Collected 
(24-hr clock) 
12 
Last dose given 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Last dose given  
 
Date:___/___/
___ 
 
Infusion Start Time: |__|__| : 
|__|__| 
 
Infusion Stop Time: |__|__| : |__|__| 
 
One copy of this Pharmacokinetic Form should be uploaded into RAVE. A second copy should be sent with the samples to the address 
listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 138 
 
 
APPENDIX I: ANTI-DRUG ANTIBODY (ADA) WORKSHEET FOR MAGROLIMAB 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg         
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Serum samples will be collected in consenting patients in red top tubes at the timepoints listed in Section 5.0. 
 
Record the exact date and time the sample is drawn.  
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
1 
Priming, Day 1 
Prior to Hu5F9-G4 (magrolimab)  
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Priming, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
2 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 1, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
3 
Cycle 2, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 2, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
4 
Cycle 3, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 3, Day 1  
 
Date:___/___/_
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 139 
 
 
__ 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
5 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 5, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
6 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 7, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
7 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 9, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
8 
Cycle 11, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Cycle 11, Day 1  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 140 
 
 
9 
End of Therapy 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Last dose given  
 
Date:___/___/_
__ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
The copy of this ADA Form should be uploaded into RAVE. A second copy should be sent with the samples to the address listed in 
Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 141 
 
 
 
APPENDIX J: FCR RECEPTOR POLYMORPHISM WORKSHEET FOR ARM A 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
PBMC samples for FcR receptor polymorphism analysis should be obtained according to instructions in Section 5.0.  
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
1 
Priming (Safety 
Lead-In), Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
The copy of this FcR Receptor Polymorphism Form should be uploaded into RAVE. A second copy should be sent with the samples to 
the address listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 142 
 
 
APPENDIX K: FCR RECEPTOR POLYMORPHISM WORKSHEET FOR ARM B 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
PBMC samples for FcR receptor polymorphism analysis should be obtained according to instructions in Section 5.0.  
 
Record the exact date and time the sample is drawn. 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
1 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
The copy of this FcR Receptor Polymorphism Form should be uploaded into RAVE. A second copy should be sent with the samples to 
the address listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 143 
 
 
APPENDIX L:  KIR PHENOTYPING WORKSHEET FOR ARM A 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
PBMC samples for KiR phenotyping should be obtained according to instructions in Section 5.0.  
 
Record the exact date and time the sample is drawn):  
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
1 
Priming (Safety 
Lead-In), day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
The copy of this KiR Phenotyping Form should be uploaded into RAVE. A second copy should be sent with the samples to the address 
listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 144 
 
 
APPENDIX M: KIR PHENOTYPING WORKSHEET FOR ARM B 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
PBMC samples for KiR receptor polymorphism analysis should be obtained according to instructions in Section 5.0.  
 
Record the exact date and time the sample is drawn. 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
1 
Cycle 1, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
 
The copy of this KiR Phenotyping Form should be uploaded into RAVE. A second copy should be sent with the samples to the address 
listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 145 
 
 
APPENDIX N: HUMAN ANTI-CHIMERA ANTIBODIES (HACA) TESTING WORKSHEET FOR 
ARM A  
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg         
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Serum samples will be collected in red top tubes at the timepoints listed in Section 5.0. 
 
Record the exact date and time the sample is drawn.  
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
1 
Cycle 1, Day 1 
Prior to dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
2 
Cycle 1, Day 5 
Immediately after dinutuximab 
infusion  
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
3 
Cycle 2, Day 1 
Prior to dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
4 
Cycle 2, Day 5 
Immediately after dinutuximab 
infusion  
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
5 
Cycle 4, Day 1 
Prior to dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 4, Day 5 
Immediately after dinutuximab 
infusion  
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
7 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
 
One copy of this HACA Form should be uploaded into RAVE. A second copy should be sent with the samples to the address listed in 
Section 5.0,, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 146 
 
 
APPENDIX O: HUMAN ANTI-CHIMERA ANTIBODIES (HACA) TESTING WORKSHEET FOR 
ARM B  
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg         
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Serum samples will be collected in consenting patients in red top tubes at the timepoints listed in Section 5.0. 
 
Record the exact date and time the sample is drawn.  
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
1 
Cycle 1, Day 8 
Prior to dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
2 
Cycle 1, Day 12 
Immediately after dinutuximab 
infusion  
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
3 
Cycle 2, Day 1 
Prior to dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
4 
Cycle 2, Day 5 
Immediately after dinutuximab 
infusion  
 
 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
5 
Cycle 4, Day 1 
Prior to dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 4, Day 5 
Immediately after dinutuximab 
infusion  
___/___/___ 
|__|__| : |__|__| 
 
 
 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample Collected 
(24-hr clock) 
7 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
 
One copy of this HACA Form should be uploaded into RAVE. A second copy should be sent with the samples to the address listed in 
Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 147 
 
 
APPENDIX P:  LUMINEX FOR PERIPHERAL CYTOKINES WORKSHEET FOR ARM A 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Plasma will be collected according to instructions in Section 5.0. 
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
1 
Priming (Safety 
Lead-In), Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
2 
Safety Lead-In, 
Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
3 
Safety Lead In, 
Day 15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Priming (Safety 
Lead-In), Week 1 
Day 1  
 
Date:___/___/
___ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
4 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
5 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 1, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
7 
Cycle 2, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 148 
 
 
8 
Cycle 2, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
9 
Cycle 2, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 2, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
10 
Cycle * 3, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 3, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
11 
Cycle 4, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 4, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
12 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 5, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
13 
Cycle 6, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 6, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 149 
 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
14 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 7, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
15 
Cycle 8, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 8, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
16 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 9, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
17 
Cycle 10, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 10, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
18 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
 
Date:___/___/
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 150 
 
 
Cycle 11, Day 1 
___ 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
19 
Cycle 12, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 12, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample 
Collected 
(24-hr clock) 
20 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
End of Therapy  
 
Date:___/___/___ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
*Fill out for as many cycles patient is on treatment  
 
One copy of this Luminex for Peripheral Cytokines Form should be uploaded into RAVE. A second copy should be sent with the samples 
to the address listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 151 
 
 
APPENDIX Q:  LUMINEX FOR PERIPHERAL CYTOKINES WORKSHEET FOR ARM B 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Plasma will be collected according to instructions in Section 5.0. 
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
1 
Priming, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
Priming, Week 1 
Day 1  
 
Date:___/___/
___ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
2 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
3 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
4 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 1, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
5 
Cycle 2, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 2, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
7 
Cycle 2, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
 
Date:___/___/
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
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Cycle 2, Day 1 
___ 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
8 
Cycle * 3, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 3, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
9 
Cycle 4, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 4, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
10 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 5, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
11 
Cycle 6, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 6, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
12 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 

                              
 
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Version Date: 02/02/2024 
 
 
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Dose on 
Cycle 7, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
13 
Cycle 8, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 8, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
14 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 9, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
15 
Cycle 10, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 10, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
16 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 11, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
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17 
Cycle 12, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Dose on 
Cycle 12, Day 1 
 
Date:___/___/
___ 
Infusion Start Time: 
|__|__| : |__|__| 
Infusion Stop Time: 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample 
Collected 
(24-hr clock) 
18 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
End of Therapy  
 
Date:___/___/___ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
*Fill out for as many cycles patient is on treatment  
 
One copy of this Luminex for Peripheral Cytokines Form should be uploaded into RAVE. A second copy should be sent with the samples 
to the address listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 
 
 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 155 
 
 
APPENDIX R:  CYTOF FOR PERIPHERAL IMMUNE SUBSETS WORKSHEET FOR ARM A  
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Mononuclear cells from blood will be collected according to instructions in Section 5.0. 
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
1 
Priming (Safety 
Lead-In), Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
2 
Safety Lead-In, 
Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
3 
Safety Lead In, 
Day 15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
4 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
5 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
7 
Cycle 2, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
8 
Cycle 2, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
9 
Cycle 2, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
Page 156 
 
 
(24-hr clock) 
10 
Cycle * 3, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
11 
Cycle 4, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
12 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
13 
Cycle 6, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
14 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
15 
Cycle 8, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
16 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Actual Time 
Sample 

                              
 
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Version Date: 02/02/2024 
 
 
Page 157 
 
 
Collected 
Collected 
(24-hr clock) 
17 
Cycle 10, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
18 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
19 
Cycle 12, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample 
Collected 
(24-hr clock) 
20 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
 
Dose on  
End of Therapy  
 
Date:___/___/___ 
Infusion Start Time: 
 |__|__| : |__|__| 
Infusion Stop Time: 
 |__|__| : |__|__| 
*Fill out for as many cycles patient is on treatment  
 
One copy of this CyTOF Form should be uploaded into RAVE. A second copy should be sent with the samples to the address listed in 
Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 158 
 
 
APPENDIX S:  CYTOF FOR PERIPHERAL IMMUNE SUBSETS WORKSHEET FOR ARM B  
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
Mononuclear cells from blood will be collected according to instructions in Section 5.0. 
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
1 
Priming, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
2 
Cycle 1, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
3 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
4 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
5 
Cycle 2, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 2, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
7 
Cycle 2, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
8 
Cycle * 3, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Actual Time 
Sample 

                              
 
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Version Date: 02/02/2024 
 
 
Page 159 
 
 
Collected 
Collected 
(24-hr clock) 
9 
Cycle 4, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
10 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
11 
Cycle 6, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
12 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
13 
Cycle 8, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
14 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
15 
Cycle 10, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
Time Point 
Scheduled Collection Time 
Actual Date 
Actual Time 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
Page 160 
 
 
No. 
Sample 
Collected 
Sample 
Collected 
(24-hr clock) 
16 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
17 
Cycle 12, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample 
Collected 
(24-hr clock) 
18 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
*Fill out for as many cycles patient is on treatment  
 
One copy of this CyTOF Form should be uploaded into RAVE. A second copy should be sent with the samples to the address listed in 
Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 161 
 
 
APPENDIX T: SAMPLE BANKING WORKSHEET FOR ARM A 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
PBMC will be collected according to instructions in Section 5.0. 
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
1 
Priming, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
2 
Safety Lead-In, 
Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
3 
Safety Lead In, 
Day 15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
4 
Cycle 1, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
5 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
7 
Cycle 2, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
8 
Cycle 2, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
9 
Cycle 2, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
Page 162 
 
 
10 
Cycle * 3, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
11 
Cycle 4, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
12 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
13 
Cycle 6, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
14 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
15 
Cycle 8, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
16 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 

                              
 
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Version Date: 02/02/2024 
 
 
Page 163 
 
 
(24-hr clock) 
17 
Cycle 10, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
18 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
19 
Cycle 12, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample 
Collected 
(24-hr clock) 
20 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
*Fill out for as many cycles patient is on treatment  
 
One copy of this Sample Banking Form should be uploaded into RAVE. A second copy should be sent with the samples to the address 
listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 

                              
 
PED-CITN-03  
 
                       
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Version Date: 02/02/2024 
 
 
Page 164 
 
 
APPENDIX U: SAMPLE BANKING WORKSHEET FOR ARM B 
COG Pt ID # _______________ 
 
                 
Please do not write patient names on this form or on samples. 
 
Patient Weight: ______kg          height ______cm.    
Hu5F9-G4 (Magrolimab) Dose: ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
Dinutuximab Dose:  
         ________ mg/kg  
  
 
Total Daily Dose: __________ mg IV infusion 
 
PBMC will be collected according to instructions in Section 5.0. 
 
Record the exact date and time the sample is drawn. 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time  
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
1 
Priming, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
2 
Cycle 1, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
3 
Cycle 1, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
4 
Cycle 1, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
5 
Cycle 2, Day 1 
Prior to Hu5F9-G4 
(magrolimab)/dinutuximab infusion 
___/___/___ 
|__|__| : |__|__| 
6 
Cycle 2, Day 8 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
7 
Cycle 2, Day 
15 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
8 
Cycle * 3, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Actual Time 
Sample 

                              
 
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Version Date: 02/02/2024 
 
 
Page 165 
 
 
Collected 
Collected 
(24-hr clock) 
9 
Cycle 4, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
10 
Cycle 5, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
11 
Cycle 6, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
12 
Cycle 7, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
13 
Cycle 8, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
14 
Cycle 9, Day 1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
15 
Cycle 10, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
Time Point 
Scheduled Collection Time 
Actual Date 
Actual Time 

                              
 
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Version Date: 02/02/2024 
 
 
Page 166 
 
 
No. 
Sample 
Collected 
Sample 
Collected 
(24-hr clock) 
16 
Cycle 11, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected 
Actual Time 
Sample 
Collected 
(24-hr clock) 
17 
Cycle 12, Day 
1 
Prior to Hu5F9-G4 (magrolimab) 
infusion 
___/___/___ 
|__|__| : |__|__| 
 
Blood Sample 
No. 
Time Point 
Scheduled Collection Time 
Actual Date 
Sample 
Collected  
Actual Time 
Sample 
Collected 
(24-hr clock) 
18 
End of Therapy  
 
___/___/___ 
|__|__| : |__|__| 
*Fill out for as many cycles patient is on treatment  
 
One copy of this Sample Banking Form should be uploaded into RAVE. A second copy should be sent with the samples to the address 
listed in Section 5.0, in addition to detailed guidelines for packaging and shipping samples. 
If this form will be used as a source document, the site personnel who collected the samples must sign and date this form below: 
Signature: _________________________________________               
 
        Date:___________________                         
(site personnel responsible for collection of samples) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                              
 
PED-CITN-03  
 
                       
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY 
 
Version Date: 02/02/2024 
 
 
Page 167 
 
 
 
APPENDIX V: CENTRAL MONITORING PLAN 
Central monitoring will be required for all patients enrolled at each site. All documents must be uploaded with 2 weeks of 
the corresponding time point or cycle. 
 
Monitored 
Data 
Protocol 
Section 
CRF 
Question/ 
Data 
Element 
Monitoring 
Conditionality 
Source 
document 
CTSU Document 
Type 
Time point 
Eligibility 
Confirmation 
of 
eligible 
diagnosis 
3.1.1 
Pending final 
CRFs 
Required 
E.g., Pathology 
report, 
CT 
report, 
MRI 
report, etc. 
Pathology Report 
and 
Radiology 
Report 
Enrollment 
Performance 
Status 
3.1.6 
Pending final 
CRFs 
Required 
E.g., 
clinical 
note, eligibility 
checklist 
Clinical Note or 
Eligibility 
Determination 
Checklist 
Adequate 
Bone 
Marrow 
function 
3.1.7 
Pending final 
CRFs 
Required 
Laboratory test 
report 
Laboratory 
Report 
Adequate 
Organ 
function 
3.1.7 
Pending final 
CRFs 
Required 
Laboratory test 
report 
Laboratory 
Report 
Adequate 
Cardiac 
Function 
3.1.16 
Pending final 
CRFs 
Required 
E.g., 
Echocardiogra
m, 
MUGA, 
Cardiac MRI 
Echocardiogram 
or Scan Report(s) 
Informed 
Consent 
3.1.15 
Pending final 
CRFs 
Required 
Informed 
consent 
(redacted 
signature pages 
with dates) 
Informed consent 
Drug Administration Elements 
Total 
Hu5F9-G4 
(magrolima
b) dose 
6.0 
Pending final 
CRFs 
Required 
Medication 
Administration 
Record (MAR) 
Treatment 
Administration 
Document 
Cycle 2 
Cycle 4 
Disease Evaluation Elements 
Tumor 
Disease 
Evaluation 
12.0 
Pending final 
CRFs 
Required 
E.g., CT report, 
MRI 
report, 
PET-CT report 
Scan Report(s) 
Cycle 2 
Cycle 4 

                              
 
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Labs/reports 
documenting 
protocol 
specific 
CTEP-AERS 
reportable 
events 
10.0 
Pending final 
CRFs 
Conditional:  
If response is 
YES, 
CM 
is 
required 
E.g., 
hospital 
admission 
report, 
laboratory 
reports, etc. 
Relevant 
Document 
Cycle 2 
Cycle 4 
 
Addressing Monitoring Findings 
In the event that this monitoring identifies unacceptable procedures or significant deviations from protocol procedures, then 
the site will need to submit a corrective action plan to COGRegComp@childrensoncologygroup.org within two weeks. 
 
In the event of significant repeated major deviations from the protocol, COGQA, in consultation with the study chair, may 
recommend that COG leadership suspend accrual at the site.