Description:
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.
Title
- Brief Title: 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
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
5F9006
- NCT ID:
NCT03558139
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Magrolimab | Hu5F9-G4 | Magrolimab + Avelumab (Part 1, Safety Run-in) |
| Avelumab | BAVENCIO® | Magrolimab + Avelumab (Part 1, Safety Run-in) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Magrolimab + Avelumab (Part 1, Safety Run-in) | Experimental | 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. | |
| Magrolimab + Avelumab (Part 2, Ovarian Cancer Expansion) | Experimental | 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. | |
Eligibility 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.
- 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 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in Cohort |
| Time Frame: | Up to 5 Weeks |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Serum concentrations of Magrolimab |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Anti-magrolimab Antibody Positivity Occurence Rate |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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). |
| Measure: | ORR Assessed by Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST) |
| Time Frame: | Up to 20 months |
| Safety Issue: | |
| Description: | ORR is defined according to Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST, Bohnsack 2014) |
| Measure: | ORR Assessed by Gynecologic Cancer InterGroup (GCIG) |
| Time Frame: | Up to 20 months |
| Safety Issue: | |
| Description: | ORR is defined according to Gynecologic Cancer InterGroup (GCIG) response criteria (Rustin 2011) |
| Measure: | Duration of Response (DOR) |
| Time Frame: | Up to 20 months |
| Safety Issue: | |
| Description: | DOR is defined as the time from the initial response until confirmed tumor progression. |
| Measure: | Time to Tumor Progression (TTP) |
| Time Frame: | Up to 20 months |
| Safety Issue: | |
| Description: | TTP is defined as the length of time from first dose of treatment combination to confirmed tumor progression. |
| Measure: | Progression-free Survival (PFS) |
| Time Frame: | Up to 20 months |
| Safety Issue: | |
| Description: | PFS is defined as the time from first dose of treatment combination to confirmed tumor progression or death, whichever occurs first. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Up to 30 months |
| Safety Issue: | |
| Description: | OS is defined as the time from first dose of treatment combination until death. |
| Measure: | Rate of Immune Cells by Immunohistochemistry |
| Time Frame: | Screening and Day 1 Cycle 3. Cycle 1 length is 35 days and Cycles 2-13 length is 28 days. |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Gilead Sciences |
Last Updated
July 27, 2021
