Study of Magrolimab (Hu5F9-G4) in Combination With Avelumab in Solid Tumor Participants and Checkpoint-Inhibitor-Naive Ovarian Cancer Participants Who Progress Within 6 Months of Prior Platinum Chemotherapy

A Phase 1b Trial of Hu5F9-G4 in Combination With Avelumab in Solid Tumor Patients and Checkpoint-Inhibitor-Naive Ovarian Cancer Patients Who Progress Within 6 Months of Prior Platinum Chemotherapy

The primary objectives of this study are to investigate the safety and tolerability of magrolimab in combination with avelumab in participants with advanced solid tumors and to confirm the safety and tolerability of this combination and evaluate the anti-tumor activity in participants with checkpoint inhibitor-naive ovarian cancer, fallopian tube cancer, and primary peritoneal carcinoma who have previously progressed within 1-6 months of receiving platinum chemotherapy.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Magrolimab; Drug: Avelumab

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Health Sciences Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Safety Run-in Cohort: Pathologically confirmed advanced solid tumors.

• Ovarian Cancer Expansion Cohort: Histologically or cytologically confirmed, epithelial ovarian, fallopian tube, or peritoneal cancer.

  • Checkpoint inhibitor naive participants.
  • Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy.
• Adequate performance status. Adequate hematological, liver, and kidney functions.
• Availability of pre-treatment tumor tissue to evaluate programmed cell death-ligand 1(PD-L1) expression.

Key Exclusion Criteria:

• Individuals with symptomatic or untreated central nervous system (CNS) metastases.
• Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) targeting agents.
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV).
• Red blood cell transfusion dependence.
• Prior organ transplantation requiring immunosuppression or active autoimmune disease.
• Significant medical diseases and/or history of uncontrolled intercurrent illness or other serious medical condition.
• Pregnancy or active breast feeding.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magrolimab 30 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in); Participants with solid tumors will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 30 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 15, 22, and 29 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Avelumab; Administered intravenously; Other Names: BAVENCIO®
Experimental: Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in); Participants with solid tumors will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Avelumab; Administered intravenously; Other Names: BAVENCIO®
Experimental: Magrolimab 45 mg/kg + Avelumab 800 mg (Part 2, Ovarian Cancer Expansion); Participants with checkpoint inhibitor-naïve ovarian cancer will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Avelumab; Administered intravenously; Other Names: BAVENCIO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in (Part 1)	A DLT was defined as a ≥ Grade 3 AE that was assessed as related to either magrolimab or avelumab that occurred during the 5-week DLT assessment period with protocol-defined allowed exceptions. Any treatment-emergent adverse event (TEAE) that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.	From the first dose date up to 5 weeks
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Treatment-emergent AEs were defined as those AEs that worsened or occurred during or after a participant's first dose of any study treatment and those existing AEs that worsened during the study and within 30 days after the last administration of any study treatment or initiation of subsequent anticancer therapy, whichever occurred first.	First dose date up to last dose plus 30 days (maximum treatment duration 18.3 months)
Percentage of Participants With Objective Response (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 in Participants With Ovarian Cancer	Objective response was defined as the percentage of participants with objective response which consisted of complete response (CR)+ partial response (PR) determined by RECIST v 1.1. CR: Disappearance of all target and all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From screening until 26.2 months (assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose and Schedule (RP2DS) of Magrolimab in Combination With Avelumab	The RP2DS was the dose of magrolimab in combination with avelumab with DLT rate less than 33% in at least 6 evaluable participants in Part 1. A DLT was defined as a ≥ Grade 3 AE that was assessed as related to either magrolimab or avelumab that occurred during the 5-week DLT assessment period with protocol-defined allowed exceptions. Any TEAE that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.	From the first dose date up to 5 weeks
Serum Concentrations of Magrolimab - Safety Run-in (Part 1)	Serum concentrations will be drawn at pre-study drug infusion (within 12 hours) on Day (D) 1 and 22 in Cycle (C) 1; Days 1 and 15 in Cycle 2; Day 1 in Cycles 3 and 4; every 3rd cycle on Day 1 until Cycle 13; 1 hour post-magrolimab infusion on Days 1 and 8 in Cycle 1; 24 hours post magrolimab infusion (Part 1 only) on Days 1 and 8 in Cycle 1; pre-study drug infusion on Day 1 in Cycles 5 and 11 (Part 1 Magrolimab 45 mg/kg only); End of Treatment (EOT) visit (up to Cycle 13); Safety Follow-up Visit (30 days after last dose of magrolimab, maximum treatment duration 18.3 months). Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days.	Predose: (C1D1, C1D22, C2D1,C2D15, C3D1, C4D1, C5D1 [only for 45 mg/kg Part 1], C7D1, C10D1, C11D1 [only for 45 mg/kg Part 1], C13D1, EOT, Safety Follow-up); 1 hour postdose: (C1D1, C1D8); 24 hours postdose: (C1D1, C1D8)
Percentage of Participants With Transient Anti-Drug Antibody to Magrolimab - Safety Run-in (Part 1)		From Day 1 of Cycle 1 up to Safety Follow-up (30 days after last dose of magrolimab, maximum treatment duration 18.3 months); Cycle 1: 35 days, subsequent Cycles: 28 days.
Percentage of Participants With Objective Response According to Gynecologic Cancer InterGroup (GCIG) Criteria in Ovarian Cancer	Objective response was defined as participants with a CR or a PR as assessed per GCIG criteria. The GCIG proposed use of both the RECIST and cancer antigen 125 (CA-125) criteria. A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Participants can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the upper limit of normal (ULN) and within 2 weeks prior to starting treatment. According to RECIST 1.1, CR was defined as disappearance of all target and all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters.	From Screening until 26.2 months (assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days)
Duration of Response (DOR) as Per GCIG Criteria in Participants With Ovarian Cancer	DOR: time from initial response (CR or PR) until disease progression. Disease progression was defined according to RECIST 1.1 but can also be based on serum CA-125. Progression based on serum CA-125 levels was defined as (1) elevated CA-125 pretreatment and normalization of CA-125 with evidence of CA-125 ≥2x ULN on 2 occasions at least 1 week apart or; (2) elevated CA-125 pretreatment, which never normalizes, with evidence of CA-125 ≥2x nadir value on 2 occasions at least 1 week apart or; (3) CA-125 in normal range pretreatment with evidence of CA-125 ≥2x ULN on 2 occasions at least 1 week apart. Progression per RECIST 1.1: At least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum measured while on study (this included baseline sum if that was smallest). In addition to relative increase of 20%, sum must also demonstrate absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesion.	From initial response until disease progression or maximum time on study (26.2 months); assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days
Progression-free Survival (PFS) in Participants With Ovarian Cancer	PFS was defined as the duration of time from dose initiation to the first date of objectively documented disease progression per RECIST 1.1 or death, whichever occurred at first. Progression as per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was 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. Unequivocal progression of existing non-target lesions. Participants who did not have documented disease progression and did not die were censored at their last tumor assessment date. Kaplan-Meier estimate was used for analysis	From first dose date to disease progression, death or maximum time on study (26.2 months); assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days
Overall Survival (OS) in Participants With Ovarian Cancer	OS was defined as the duration of time from dose initiation to the date of death due to any cause. Participants who did not die were censored at their last known alive date. Kaplan-Meier estimate was used for analysis.	From first dose date to death or maximum time on study (26.2 months)
Percent Change of Immune Cells by Immunohistochemistry in Participants With Ovarian Cancer	Paired tumor biopsies from participants with ovarian cancer were analyzed by CD68 immunohistochemistry staining to evaluate the impact of magrolimab in combination with avelumab on macrophage frequency in the tumor microenvironment.	Screening and Day 1 Cycle 3 (Cycle 3 duration: 28 days)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Lakhani NJ, Patnaik A, Liao JB, et al. A phase 1b study of the anti-CD47 antibody magrolimab with the PD-L1 inhibitor avelumab in solid tumor & ovarian cancer patients [Abstract]. American Society of Clinical Oncology (ASCO)-Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Symposium; 2020 06-08 February. Orlando, FL.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2018
• Primary Completion (Actual): December 3, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: May 30, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab; Magrolimab
• Other Study ID Numbers: 5F9006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No