Clinical trial NCT03558139: Study 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2018-06-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 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.


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 cluster of differentiation 47 (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.

Primary outcomes:
measure: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in (Part 1)
timeFrame: From the first dose date up to 5 weeks
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to last dose plus 30 days (maximum treatment duration 18.3 months)
measure: Percentage of Participants With Objective Response (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 in Participants With Ovarian Cancer
timeFrame: From screening until 26.2 months (assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days)
Secondary outcomes:
measure: Recommended Phase 2 Dose and Schedule (RP2DS) of Magrolimab in Combination With Avelumab
timeFrame: From the first dose date up to 5 weeks
measure: Serum Concentrations of Magrolimab - Safety Run-in (Part 1)
timeFrame: Predose: (C1D1, C1D22, C2D1,C2D15, C3D1, C4D1, C5D1 [only for 45 mg/kg Part 1], C7D1, C10D1, C11D1 [only for 45 mg/kg Part 1], C13D1, EOT, Safety Follow-up); 1 hour postdose: (C1D1, C1D8); 24 hours postdose: (C1D1, C1D8)
measure: Percentage of Participants With Transient Anti-Drug Antibody to Magrolimab - Safety Run-in (Part 1)
timeFrame: From Day 1 of Cycle 1 up to Safety Follow-up (30 days after last dose of magrolimab, maximum treatment duration 18.3 months); Cycle 1: 35 days, subsequent Cycles: 28 days.
measure: Percentage of Participants With Objective Response According to Gynecologic Cancer InterGroup (GCIG) Criteria in Ovarian Cancer
timeFrame: From Screening until 26.2 months (assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days)
measure: Duration of Response (DOR) as Per GCIG Criteria in Participants With Ovarian Cancer
timeFrame: From initial response until disease progression or maximum time on study (26.2 months); assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days
measure: Progression-free Survival (PFS) in Participants With Ovarian Cancer
timeFrame: From first dose date to disease progression, death or maximum time on study (26.2 months); assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days
measure: Overall Survival (OS) in Participants With Ovarian Cancer
timeFrame: From first dose date to death or maximum time on study (26.2 months)
measure: Percent Change of Immune Cells by Immunohistochemistry in Participants With Ovarian Cancer
timeFrame: Screening and Day 1 Cycle 3 (Cycle 3 duration: 28 days)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center
state: Oklahoma
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Lakhani NJ, Patnaik A, Liao JB, et al. A phase 1b study of the anti-CD47 antibody magrolimab with the PD-L1 inhibitor avelumab in solid tumor & ovarian cancer patients [Abstract]. American Society of Clinical Oncology (ASCO)-Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Symposium; 2020 06-08 February. Orlando, FL.