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

NCT02953782 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 5F9004
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 8

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

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Dose Limiting Toxicities (DLT)

  DLT was defined as any Grade (GR) 3 or greater adverse event (AE) that was assessed as related to study treatment with the exceptions of: GR 3: anemia (hemolytic anemia that is medically significant tis considered a DLT), indirect/unconjugated hyperbilirubinemia, electrolyte abnormalities, elevation in alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase that resolved to ≤ Grade 2 with supportive care within 1 week and is not associated with other clinically significant consequences; nausea, vomiting, or diarrhea that resolved to ≤ Grade 2 with supportive care within 72 hours; fatigue that resolved to ≤ Grade 2 within 2 weeks on study; drug-related infusion reactions in the absence of an optimal pretreatment regimen; tumor lysis syndrome or electrolyte disturbances, hypomagnesemia, that resolved to ≤ Grade 2 or baseline within 1 week; GR 3 or 4: lymphopenia or leukopenia.

  From first dose up to Day 28

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

  An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product. A TEAE was defined as AEs worsening or occurring during or after a participant's first exposure to study drug and within 30 days after the last administration of study drug or initiation of new anticancer therapy, whichever occurred first.

  From first dose date up to last dose date plus 30 days (maximum: 15.3 months)

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Objective response rate 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 38.89 months (assessed on Day 1 of Cycle 3 then every 8 weeks [Q8W] from Cycle 5 onwards up to 38.89 months; 1 cycle = 4 weeks)

Secondary Outcomes (9)

• Pharmacokinetic (PK) Parameter: Cmax of Magrolimab

  Pre-magrolimab dose (within 12 hours) and 1-hour post-magrolimab dose (infusion duration = approximately 3 hours on Day 1 and 2 hours on other days) on Days 1 (Cycle 1 Day 1), 8 (Cycle 1 Day 8), and 29 (Cycle 2 Day 1) (1 cycle = 4 weeks)

• PK Parameter: Tmax of Magrolimab

  Pre-magrolimab dose (within 12 hours) and 1-hour post-magrolimab dose (infusion duration = approximately 3 hours on Day 1 and 2 hours on other days) on Days 8 (Cycle 1 Day 8) and 29 (Cycle 2 Day 1) (1 cycle = 4 weeks)

• PK Parameter: AUClast of Magrolimab

  Pre-magrolimab dose (within 12 hours) and 1-hour post-magrolimab dose (infusion duration = approximately 3 hours on Day 1 and 2 hours on other days) on Days 8 (Cycle 1 Day 8) and 29 (Cycle 2 Day 1) (1 cycle = 4 weeks)

• PK Parameter: AUCtau of Magrolimab

  Pre-magrolimab dose (within 12 hours) and 1-hour post-magrolimab dose (infusion duration = approximately 3 hours on Day 1 and 2 hours on other days) on Days 8 (Cycle 1 Day 8) and 29 (Cycle 2 Day 1) (1 cycle = 4 weeks)

• Percentage of Participants With Anti-drug Antibodies (ADA)

  Baseline; post-treatment (assessed continuously up to 30 days after last dose; maximum 15.3 months )

Study Arms (8)

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

EXPERIMENTAL

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).

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

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

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Cetuximab

Interventions

Magrolimab DRUG

Administered intravenously

Also known as: Hu5F9-G4

Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2; Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2; Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2; Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2; Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2; Phase 2 Cohort 1 (KRASwt): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2; Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2; Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2

Cetuximab DRUG

Administered intravenously

Also known as: ERBITUX®

Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2; Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2; Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2; Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2; Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2; Phase 2 Cohort 1 (KRASwt): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2; Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2; Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (8)

UCLA

Los Angeles, California, 90404, United States

Location

Stanford University

Palo Alto, California, 94305-5757, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

START Midwest

Grand Rapids, Michigan, 49503, United States

Location

UPENN

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Md Anderson

Houston, Texas, 77030, United States

Location

START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

magrolimab; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: November 1, 2016
• First Posted: November 3, 2016
• Study Start: November 2, 2016
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: March 1, 2021
• Results First Posted: March 1, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)