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

Gilead Sciences

Status and phase: Completed; Phase 2; Phase 1

Conditions: Solid Tumor; Colorectal Cancer

Treatments: Drug: Magrolimab; Drug: Cetuximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02953782

5F9004

Details and patient eligibility

About

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).

Enrollment: 78 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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78 participants in 8 patient groups

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

Experimental group

Description:

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).

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab

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

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: Magrolimab