Trial 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
Study Details
Study Description
Brief Summary
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 based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Eisenhauer 2009) 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Magrolimab + Avelumab (Part 1, Safety Run-in) Dose Level 1: Participants with solid tumors will be given a starting priming dose of 1 mg/kg magrolimab in Week 1, followed by 30 mg/kg weekly for 4 doses (Cycle 1). Starting in Cycle 2, magrolimab 30 mg/kg will be given every 2 weeks. The magrolimab dose will be combined with avelumab 800 mg given once every 2 weeks. Based on Dose Limiting Toxicities (DLTs) assessment in Dose Level 1 Cycle 1; additional participants will be enrolled and administered Dose Level 2. Dose Level 2: Participants with solid tumors will be given a starting priming dose of 1 mg/kg magrolimab in Week 1, followed by 45 mg/kg on Days 8,11,15, 22 and 29 for Cycle 1, continuing weekly in Cycle 2 on Days 1, 8, 15 and 22. Starting in Cycle 3, magrolimab 45 mg/kg will be given every 2 weeks. The magrolimab dose will be combined with avelumab 800 mg given once every 2 weeks. Additional lower or higher dose levels may be explored after reviewing all available clinical data. |
Drug: Magrolimab
Administered intravenously
Other Names:
Drug: Avelumab
Administered intravenously
Other Names:
|
| Experimental: Magrolimab + Avelumab (Part 2, Ovarian Cancer Expansion) After Part 1 Safety Run-in has completed and the recommended expansion dose(s) for magrolimab is determined, participants with ovarian cancer will be administered the recommended magrolimab dose(s) combined with avelumab 800 mg given once every 2 weeks. |
Drug: Magrolimab
Administered intravenously
Other Names:
Drug: Avelumab
Administered intravenously
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in Cohort [Up to 5 Weeks]
A DLT is defined as any Grade 3 or greater adverse event (AE) that is assessed as related to at least 1 study drug that occurs during the 5-week DLT Assessment Period, defined as the first 5 weeks of treatment for each participant.
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events [First dose date up to 20 months plus 30 days]
- Objective Response Rate (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) [Up to 20 months]
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Secondary Outcome Measures
- Serum concentrations of Magrolimab [C1D1 & D22; C2D1 & D15; C3&C4 D1 & every third cycle, D1 after C4 until C13; EOT (up to C13+14D); SFU (30±7D after last dose of magrolimab); at 1h(±15 min) after magrolimab infusion for C1D1 & D8; at 24 h(±15 min) after magrolimab infusion for C1D2 & D9]
Serum concentrations will be drawn at pre-study drug (magrolimab and avelumab) infusion for Cycle 1 Days 1 & 22, Cycle 2 Days 1 & 15, Cycles 3 and 4, Day 1, and every third cycle, Day 1 after Cycle 4 until Cycle 13, End of Treatment (EOT) (up to Cycle 13 + 14 days), and Safety Follow-up Visit (SFU) (30 days ± 7 days after last dose of magrolimab); at 1 hour (± 15 minutes) after magrolimab infusion for Cycle 1 Days 1 & 8; at 24 hours (± 15 minutes) after magrolimab infusion for Cycle 1 Days 2 & 9. Cycle 1 length is 35 days Cycles 2-13 length is 28 days C=Cycle D=day(s) h=hours min=minutes
- Anti-magrolimab Antibody Positivity Occurence Rate [Days 1 for Cycles 1, 2, 3, & 4 & every third cycle after Cycle 4 until Cycle 13; EOT (up to Cycle 13+14 days); SFU (30±7 days after last dose of magrolimab); Cycle 1 length is 35 days and Cycles 2-13 length is 28 days]
Anti-magrolimab antibody positivity will be assessed at pre-study drug (magrolimab and avelumab) infusion Day 1 for Cycles 1, 2, 3 and 4, and then every third cycle after Cycle 4 until Cycle 13, End of Treatment (EOT) (up to Cycle 13 + 14 days), and Safety Follow-up Visit (SFU) (30 days ± 7 days after last dose of magrolimab).
- ORR Assessed by Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST) [Up to 20 months]
ORR is defined according to Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST, Bohnsack 2014)
- ORR Assessed by Gynecologic Cancer InterGroup (GCIG) [Up to 20 months]
ORR is defined according to Gynecologic Cancer InterGroup (GCIG) response criteria (Rustin 2011)
- Duration of Response (DOR) [Up to 20 months]
DOR is defined as the time from the initial response until confirmed tumor progression.
- Time to Tumor Progression (TTP) [Up to 20 months]
TTP is defined as the length of time from first dose of treatment combination to confirmed tumor progression.
- Progression-free Survival (PFS) [Up to 20 months]
PFS is defined as the time from first dose of treatment combination to confirmed tumor progression or death, whichever occurs first.
- Overall Survival (OS) [Up to 30 months]
OS is defined as the time from first dose of treatment combination until death.
- Rate of Immune Cells by Immunohistochemistry [Screening and Day 1 Cycle 3. Cycle 1 length is 35 days and Cycles 2-13 length is 28 days.]
Eligibility Criteria
Criteria
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.
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Checkpoint inhibitor naive participants.
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Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy.
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Adequate performance status. Adequate hematological, liver, and kidney functions.
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Availability of pre-treatment tumor tissue to evaluate programmed cell death-ligand 1(PD-L1) expression.
Key Exclusion Criteria:
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Individuals with symptomatic or untreated central nervous system (CNS) metastases.
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Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents.
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Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV).
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Red blood cell transfusion dependence.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 2 | START Midwest | Grand Rapids | Michigan | United States | 49546 |
| 3 | Oklahoma University Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 4 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75235 |
| 5 | South Texas Accelerated Research Therapeutics, LLC | San Antonio | Texas | United States | 78229 |
| 6 | University of Washington | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Gilead Sciences
- Merck KGaA, Darmstadt, Germany
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 5F9006