Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE May 30, 2018
First Posted Date  ICMJE June 15, 2018
Last Update Posted Date July 27, 2021
Actual Study Start Date  ICMJE May 23, 2018
Actual Primary Completion Date December 3, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • 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.
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 20 months plus 30 days ]
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 13, 2018)
  • Dose-Limiting Toxicities [ Time Frame: 35-Days ]
    Number of participants with dose-limiting toxicities and treatment-related adverse events as assessed by CTCAE v4.03.
  • Objective Response Rate [ Time Frame: 8 Weeks ]
    Evaulate anti-tumor activity based on RECIST v1.1, irRECIST, and Gynecologic Cancer Intergroup (GCIG) response criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • 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
  • 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).
  • 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)
  • 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)
  • Duration of Response (DOR) [ Time Frame: Up to 20 months ]
    DOR is defined as the time from the initial response until confirmed tumor progression.
  • 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.
  • 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.
  • Overall Survival (OS) [ Time Frame: Up to 30 months ]
    OS is defined as the time from first dose of treatment combination until death.
  • 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. ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Drug: Magrolimab
    Administered intravenously
    Other Name: Hu5F9-G4
  • Drug: Avelumab
    Administered intravenously
    Other Name: BAVENCIO®
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Magrolimab
    • Drug: Avelumab
  • 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.
    Interventions:
    • Drug: Magrolimab
    • Drug: Avelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2020)
34
Original Estimated Enrollment  ICMJE
 (submitted: June 13, 2018)
32
Actual Study Completion Date  ICMJE December 3, 2020
Actual Primary Completion Date December 3, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03558139
Other Study ID Numbers  ICMJE 5F9006
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP