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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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ClinicalTrials.gov Identifier: NCT03558139
Recruitment Status : Completed
First Posted : June 15, 2018
Last Update Posted : July 27, 2021
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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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
Ovarian Cancer Drug: Magrolimab Drug: Avelumab Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2018
Actual Primary Completion Date : December 3, 2020
Actual Study Completion Date : December 3, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Avelumab

Arms and Interventions
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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 Name: Hu5F9-G4

Drug: Avelumab
Administered intravenously
Other Name: BAVENCIO®
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 Name: Hu5F9-G4

Drug: Avelumab
Administered intravenously
Other Name: BAVENCIO®


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in Cohort [ Time Frame: 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.

  2. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 20 months plus 30 days ]
  3. Objective Response Rate (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: 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 :
  1. 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 ]

    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

  2. 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 ]
    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).

  3. 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 ]
    ORR is defined according to Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-related Response Criteria (irRECIST, Bohnsack 2014)

  4. ORR Assessed by Gynecologic Cancer InterGroup (GCIG) [ Time Frame: Up to 20 months ]
    ORR is defined according to Gynecologic Cancer InterGroup (GCIG) response criteria (Rustin 2011)

  5. Duration of Response (DOR) [ Time Frame: Up to 20 months ]
    DOR is defined as the time from the initial response until confirmed tumor progression.

  6. Time to Tumor Progression (TTP) [ Time Frame: Up to 20 months ]
    TTP is defined as the length of time from first dose of treatment combination to confirmed tumor progression.

  7. Progression-free Survival (PFS) [ Time Frame: 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.

  8. Overall Survival (OS) [ Time Frame: Up to 30 months ]
    OS is defined as the time from first dose of treatment combination until death.

  9. 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. ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03558139


Locations
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United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Michigan
START Midwest
Grand Rapids, Michigan, United States, 49546
United States, Oklahoma
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Gilead Sciences
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Gilead Study Director Gilead Sciences
More Information
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03558139    
Other Study ID Numbers: 5F9006
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: July 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
 Urogenital Neoplasms
Genital Diseases
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Avelumab
Magrolimab
Antineoplastic Agents, Immunological
Antineoplastic Agents