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

NCT03558139 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 5F9006
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 6

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in (Part 1)

  A DLT was defined as a ≥ Grade 3 AE that was assessed as related to either magrolimab or avelumab that occurred during the 5-week DLT assessment period with protocol-defined allowed exceptions. Any treatment-emergent adverse event (TEAE) that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.

  From the first dose date up to 5 weeks

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

  An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Treatment-emergent AEs were defined as those AEs that worsened or occurred during or after a participant's first dose of any study treatment and those existing AEs that worsened during the study and within 30 days after the last administration of any study treatment or initiation of subsequent anticancer therapy, whichever occurred first.

  First dose date up to last dose plus 30 days (maximum treatment duration 18.3 months)

• Percentage of Participants With Objective Response (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 in Participants With Ovarian Cancer

  Objective response was defined as the percentage of participants with objective response which consisted of complete response (CR)+ partial response (PR) determined by RECIST v 1.1. CR: Disappearance of all target and all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  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 (8)

• Recommended Phase 2 Dose and Schedule (RP2DS) of Magrolimab in Combination With Avelumab

  From the first dose date up to 5 weeks

• Serum Concentrations of Magrolimab - Safety Run-in (Part 1)

  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)

• Percentage of Participants With Transient Anti-Drug Antibody to Magrolimab - Safety Run-in (Part 1)

  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.

• Percentage of Participants With Objective Response According to Gynecologic Cancer InterGroup (GCIG) Criteria in Ovarian Cancer

  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)

• Duration of Response (DOR) as Per GCIG Criteria in Participants With Ovarian Cancer

  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

Study Arms (3)

Magrolimab 30 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in)

EXPERIMENTAL

Participants with solid tumors will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 30 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 15, 22, and 29 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Drug: Magrolimab; Drug: Avelumab

Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in)

EXPERIMENTAL

Participants with solid tumors will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Drug: Magrolimab; Drug: Avelumab

Magrolimab 45 mg/kg + Avelumab 800 mg (Part 2, Ovarian Cancer Expansion)

EXPERIMENTAL

Participants with checkpoint inhibitor-naïve ovarian cancer will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Drug: Magrolimab; Drug: Avelumab

Interventions

Magrolimab DRUG

Administered intravenously

Also known as: Hu5F9-G4

Magrolimab 30 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in); Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in); Magrolimab 45 mg/kg + Avelumab 800 mg (Part 2, Ovarian Cancer Expansion)

Avelumab DRUG

Administered intravenously

Also known as: BAVENCIO®

Magrolimab 30 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in); Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in); Magrolimab 45 mg/kg + Avelumab 800 mg (Part 2, Ovarian Cancer Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (6)

University of Chicago

Chicago, Illinois, 60637, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  RESULT

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

magrolimab; avelumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: June 15, 2018
• Study Start: May 23, 2018
• Primary Completion: December 3, 2020
• Study Completion: December 3, 2020
• Last Updated: April 1, 2024
• Results First Posted: April 1, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)