Back to resultsTrial 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
Primary Purpose
Ovarian Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Magrolimab
Avelumab
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer
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.
Sites / Locations
- University of Chicago
- START Midwest
- Oklahoma University Health Sciences Center
- University of Texas Southwestern Medical Center
- South Texas Accelerated Research Therapeutics, LLC
- University of Washington
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Magrolimab + Avelumab (Part 1, Safety Run-in)
Magrolimab + Avelumab (Part 2, Ovarian Cancer Expansion)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in Cohort
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
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST)
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
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
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)
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)
ORR is defined according to Gynecologic Cancer InterGroup (GCIG) response criteria (Rustin 2011)
Duration of Response (DOR)
DOR is defined as the time from the initial response until confirmed tumor progression.
Time to Tumor Progression (TTP)
TTP is defined as the length of time from first dose of treatment combination to confirmed tumor progression.
Progression-free Survival (PFS)
PFS is defined as the time from first dose of treatment combination to confirmed tumor progression or death, whichever occurs first.
Overall Survival (OS)
OS is defined as the time from first dose of treatment combination until death.
Rate of Immune Cells by Immunohistochemistry
Full Information
NCT ID
NCT03558139
First Posted
May 30, 2018
Last Updated
July 26, 2021
Sponsor
Gilead Sciences
Collaborators
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT03558139
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
May 23, 2018 (Actual)
Primary Completion Date
December 3, 2020 (Actual)
Study Completion Date
December 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
Merck KGaA, Darmstadt, Germany
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Magrolimab + Avelumab (Part 1, Safety Run-in)
Arm Type
Experimental
Arm Description
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.
Arm Title
Magrolimab + Avelumab (Part 2, Ovarian Cancer Expansion)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Magrolimab
Other Intervention Name(s)
Hu5F9-G4
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Avelumab
Other Intervention Name(s)
BAVENCIO®
Intervention Description
Administered intravenously
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in Cohort
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.
Time Frame
Up to 5 Weeks
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame
First dose date up to 20 months plus 30 days
Title
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST)
Description
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.
Time Frame
Up to 20 months
Secondary Outcome Measure Information:
Title
Serum concentrations of Magrolimab
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
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
Title
Anti-magrolimab Antibody Positivity Occurence Rate
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).
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
Title
ORR Assessed by Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST)
Description
ORR is defined according to Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST, Bohnsack 2014)
Time Frame
Up to 20 months
Title
ORR Assessed by Gynecologic Cancer InterGroup (GCIG)
Description
ORR is defined according to Gynecologic Cancer InterGroup (GCIG) response criteria (Rustin 2011)
Time Frame
Up to 20 months
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the initial response until confirmed tumor progression.
Time Frame
Up to 20 months
Title
Time to Tumor Progression (TTP)
Description
TTP is defined as the length of time from first dose of treatment combination to confirmed tumor progression.
Time Frame
Up to 20 months
Title
Progression-free Survival (PFS)
Description
PFS is defined as the time from first dose of treatment combination to confirmed tumor progression or death, whichever occurs first.
Time Frame
Up to 20 months
Title
Overall Survival (OS)
Description
OS is defined as the time from first dose of treatment combination until death.
Time Frame
Up to 30 months
Title
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
START Midwest
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49546
Country
United States
Facility Name
Oklahoma University Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
South Texas Accelerated Research Therapeutics, LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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