Study of Magrolimab (Hu5F9-G4) in Combination With Cetuximab in Participants With Solid Tumors and Advanced Colorectal Cancer

NCT ID: NCT02953782

Last Updated: 2021-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-02
• Study Completion Date: 2020-02-10

Brief Summary

The primary objectives of this study are: (Phase 1b) to investigate the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) for magrolimab in combination with cetuximab; and (Phase 2) to evaluate overall response rate (ORR) of magrolimab in combination with cetuximab in participants with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutant and KRAS wild-type colorectal cancer (CRC).

Conditions

Solid Tumor; Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2

Participants with solid tumor will receive a priming dose of magrolimab 1 mg/kg of body weight by intravenous (IV) infusion (approximately 3 hours infusion) on Day 1 followed by a maintenance dose of magrolimab 10 mg/kg of body weight by IV infusion (approximately 2 hours infusion) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 300 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 200 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. After Cycle 1 and thereafter, weekly maintenance dose for both magrolimab and cetuximab, will start on Day 1. Each cycle will consist of 4 weeks (28 days). Cetuximab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented progressive disease (PD).

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2

Participants with solid tumor will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approximately 3 hours infusion) on Day 1 followed by a maintenance dose of magrolimab 10 mg/kg of body weight by IV infusion (approximately 2 hours infusion) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. After Cycle 1 and thereafter, weekly maintenance dose for both magrolimab and cetuximab, will start on Day 1. Each cycle will consist of 4 weeks (28 days). Cetuximab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2

Participants with solid tumor will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approximately 3 hours infusion) on Day 1 followed by a maintenance dose of magrolimab 20 mg/kg of body weight by IV infusion (approximately 2 hours infusion) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. After Cycle 1 and thereafter, weekly maintenance dose for both magrolimab and cetuximab, will start on Day 1. Each cycle will consist of 4 weeks (28 days). Cetuximab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2

Participants with solid tumor will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approximately 3 hours infusion) on Day 1 followed by a maintenance dose of magrolimab 30 mg/kg of body weight by IV infusion (approximately 2 hours infusion) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. After Cycle 1 and thereafter, weekly maintenance dose for both magrolimab and cetuximab, will start on Day 1. Each cycle will consist of 4 weeks (28 days). Cetuximab will be administered 1 hour prior to magrolimab infusion on days when both were given. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2

Participants with solid tumor will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approximately 3 hours infusion) on Day 1 followed by a maintenance dose of magrolimab 45 mg/kg of body weight by IV infusion (approximately 2 hours infusion) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. Participants will also receive a loading dose of magrolimab 45 mg/kg on Day 11 of Cycle 1. After Cycle 1, maintenance dose for both magrolimab and cetuximab will start on Day 1 with weekly dose in Cycle 2 and bi-weekly dose in Cycle 3 onwards for magrolimab. Each cycle will consist of 4 weeks. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 2 Cohort 1 (KRASwt): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2

Participants with advanced colorectal cancer (CRC) who are KRAS wild type (KRASwt) and are refractory to anti-EGFRmAb therapy will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approximately 3 hours) on Day 1 followed by a maintenance dose of magrolimab 30 mg/kg of body weight by IV infusion (approximately 2 hours) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. After Cycle 1, maintenance dose for both magrolimab and cetuximab will start on Day 1; Days 8 and 22 are removed from Cycle 2 onwards for magrolimab. Each cycle will consist of 4 weeks. Cetuximab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2

Participants with advanced CRC with KRAS mutation (KRASm) who have progressed or are not candidates for oxaliplatin or irinotecan-based therapy will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approximately 3 hours infusion) on Day 1 followed by a maintenance dose of magrolimab 30 mg/kg of body weight by IV infusion (approximately 2 hours infusion) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. After Cycle 1, maintenance dose for both magrolimab and cetuximab will start on Day 1; Days 8 and 22 are removed from Cycle 2 onwards for magrolimab. Each cycle will consist of 4 weeks. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2

Participants with advanced CRC with KRASm who have progressed or are not candidates for oxaliplatin or irinotecan-based therapy will receive a priming dose of magrolimab 1 mg/kg of body weight by IV infusion (approx. 3 hours) on Day 1 followed by a maintenance dose of magrolimab 45 mg/kg of body weight by IV infusion (approx. 2 hours) weekly starting on Day 8 followed by Days 15 and 22 in combination with cetuximab at a loading dose of 400 mg/m\^2 infused over 120-minutes on Day 8 followed by a weekly maintenance dose of 250 mg/m\^2 infusions given over 60 minutes on Days 15 and 22, in Cycle 1. Participants will also receive a loading dose of magrolimab 45 mg/kg of body weight on Day 11 of Cycle 1. After Cycle 1, maintenance dose for both magrolimab and cetuximab will start on Day 1; Days 8 and 22 are removed from Cycle 3 onwards for magrolimab. Each cycle will consist of 4 weeks. Treatment will be administered until unacceptable toxicity, voluntary withdrawal, or documented PD.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Cetuximab

Intervention Type: DRUG

Administered intravenously

Interventions

Magrolimab

Administered intravenously

Intervention Type: DRUG

Cetuximab

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

Hu5F9-G4; ERBITUX®

Eligibility Criteria

Inclusion Criteria

• Histological Diagnosis

• Phase 1b only: Advanced solid malignancy with an emphasis on colorectal cancer (CRC), head and neck, breast, pancreatic and ovarian cancers who have been treated with at least one regimen of prior systemic therapy, or who refuse systemic therapy, and for which there is no curative therapy available.
• Phase 2:
• KRAS Mutant CRC: Advanced KRAS mutant CRC who have progressed or are ineligible for both irinotecan and oxaliplatin based chemotherapy
• KRAS Wild-Type CRC: Advanced KRAS wild type CRC who have progressed or are ineligible for fluoropyrimidine, irinotecan, and oxaliplatin based chemotherapy and who are relapsed or refractory to at least 1 prior systemic therapy that included an anti-epidermal growth factor receptor (EGFR) antibody, such as cetuximab, panitumumab or others.
• Adequate performance status and hematological, liver, and kidney function
• Phase 2 only: Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy

Exclusion Criteria

• Active brain metastases
• Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) targeting agents.
• Phase 2 only: second malignancy within the last 3 years.
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV)
• Pregnancy or active breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

California Institute for Regenerative Medicine (CIRM)

OTHER

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

UCLA

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

Wayne State University

Detroit, Michigan, United States

START Midwest

Grand Rapids, Michigan, United States

UPENN

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Md Anderson

Houston, Texas, United States

START Center for Cancer Care

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

5F9004

Identifier Type: -

Identifier Source: org_study_id