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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02953782
Recruitment Status : Completed
First Posted : November 3, 2016
Last Update Posted : October 22, 2020
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Gilead Sciences

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).

Condition or disease Intervention/treatment Phase
Solid Tumor Colorectal Cancer Drug: Magrolimab Drug: Cetuximab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Trial of Hu5F9-G4 in Combination With Cetuximab in Patients With Solid Tumors and Advanced Colorectal Cancer
Actual Study Start Date : November 2, 2016
Actual Primary Completion Date : February 10, 2020
Actual Study Completion Date : February 10, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: Magrolimab + Cetuximab (Phase 1b, Dose escalation)

Participants with advanced solid tumors will be given a starting priming dose of 1 mg/kg magrolimab on Day 1 followed by 10 mg/kg maintenance doses on Days 8, 15, and 22. Cetuximab will be given at a reduced dose of 300 mg/m^2 on Day 8 followed by 200 mg/m^2 on Days 15 and 22. Magrolimab and cetuximab will continue to be given weekly during subsequent cycles.

Based on dose limiting toxicities (DLTs) observed, additional participants will be enrolled and administered priming dose of 1 mg/kg magrolimab followed by escalating maintenance doses of up to 45 mg/kg + cetuximab up to 250 mg/m^2 to determine the recommended Phase 2 dose (RP2D) for magrolimab in combination with cetuximab.

Drug: Magrolimab
Administered intravenously
Other Name: Hu5F9-G4

Drug: Cetuximab
Administered intravenously
Other Name: ERBITUX®

Experimental: Magrolimab + Cetuximab (Phase 2, KRAS Wild-Type)
After the dose escalating phase (Phase 1b) has completed and an RP2D for magrolimab in combination with cetuximab is determined, participants with advanced CRC who have KRAS wild-type tumors will receive the RP2D of magrolimab in combination with cetuximab 400 mg/m^2 on Day 8 followed by 250 mg/m^2 weekly.
Drug: Magrolimab
Administered intravenously
Other Name: Hu5F9-G4

Drug: Cetuximab
Administered intravenously
Other Name: ERBITUX®

Experimental: Magrolimab + Cetuximab (Phase 2, KRAS Mutant)
After the RP2D tolerability is confirmed in the KRAS wild-type cohort, participants with advanced CRC who have KRAS mutant will receive the RP2D of magrolimab in combination with cetuximab 400 mg/m^2 on Day 8 followed by 250 mg/m^2 weekly.
Drug: Magrolimab
Administered intravenously
Other Name: Hu5F9-G4

Drug: Cetuximab
Administered intravenously
Other Name: ERBITUX®




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Phase 1b [ Time Frame: Up to 4 Weeks ]
    A DLT is defined as any Grade 3 or greater adverse event (AE) that is assessed as related to study treatment that occurs during the 4-week DLT observation period, defined as the first 4 weeks of treatment.

  2. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 39 months plus 30 days ]
  3. Objective Response Rate (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Up to 33 months ]
    ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.


Secondary Outcome Measures :
  1. Serum Concentrations of Magrolimab [ Time Frame: Up to 33 months plus 30 days ]

    Phase 1b: Pre-magrolimab infusion (within 12 h): C1 Days 1,8,15 & 22, C2 Days 1,8,15 & 22, C3 Days 1 & 8, C4 to C5 Day 1, every other cycle Day 1 after C5 until C13, End of Treatment (EOT) (up to cycle 13+7 days), Safety Follow-up (SFU) (30±7 days after last dose of magrolimab); 1 h (±15 min) after magrolimab infusion: C1 Days 1,8,15 & 22, C2 Days 1 & 8, C3 Days 1 & 8, C4 to C5 Day 1, every other cycle Day 1 after C5 until C13; 24 h (±8h) after magrolimab infusion: C1 Day 9, C2 Day 2; 72 h (±12 h) after magrolimab infusion: C1 Day 11, C2 Day 4;

    Phase 2: Pre-magrolimab infusion (within 12 h): C1 Days 1,8 & 15, C2 Days 1 & 15, C3 to C5 Day 1, every fourth cycle, Day 1 after C5 until C13, EOT, SFU; 1 h (±15 min) after magrolimab infusion: C1 Days 1,8 & 15, C2 Days 1 & 15, C3 to C5 Day 1, every fourth cycle, Day 1 after C5 until C13, EOT, SFU

    C=Cycle, h=hours, min=minutes, Cycle length is 28 Days


  2. Anti-magrolimab Antibody Positivity Occurence Rate [ Time Frame: Pre- drug infusion (magrolimab + cetuximab) for Cycle 1 Days 1 & 8, Cycles 2 to 13 Days 1, End of Treatment (up the Cycle 13 + 7 days), and SFU (30 days ± 7 days after last dose of magrolimab); cycle length = 28 days ]
  3. Anti-cetuximab Antibody Positivity Occurence Rate [ Time Frame: Pre-study drug infusion (magrolimab + cetuximab) for Cycle 1 Days 1 & 8, Cycles 2 to 13 Days 1, End of Treatment (up the Cycle 13 + 7 days), and SFU (30 days ± 7 days after last dose of cetuximab); cycle length = 28 days ]
  4. Disease Control Rate (DCR) [ Time Frame: Up to 34 months ]
    Disease control is defined as CR+PR+ stable disease (SD) determined by RECIST v 1.1.

  5. Duration of Response (DOR) [ Time Frame: Up to 33 months ]
    DOR is measured from when the first (objective) response is met (i.e., CR or PR) until the first date of objectively documented progressive disease.

  6. Progression-free Survival (PFS) [ Time Frame: Up to 33 months ]
    PFS is measured from dose initiation until the first date of objectively documented progression disease or death.

  7. Overall Survival (OS) [ Time Frame: Up to 39 months ]
    OS is measured from dose initiation until death.

  8. Time to Progression (TTP) [ Time Frame: Up to 33 months ]
    TTP is measured from dose initiation until the first date of objectively documented progressive disease.

  9. Objective Response Rate (ORR) Assessed the Response Evaluation Criteria in Solid Tumors Guidelines for Use in Trials Testing Immunotherapeutics (iRECIST) [ Time Frame: Up to 33 months ]
    ORR is defined as the proportion of participants who achieve immune complete response (iCR) + immune partial response (iPR) determined by Response Evaluation Criteria in Solid Tumors guidelines for use in trials testing immunotherapeutics (iRECIST)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 both 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 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 HIV
  • Pregnancy or active breastfeeding

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953782


Locations
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United States, California
UCLA
Los Angeles, California, United States, 90404
Stanford University
Palo Alto, California, United States, 94305-5757
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
START Midwest
Grand Rapids, Michigan, United States, 49503
United States, Pennsylvania
UPENN
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Md Anderson
Houston, Texas, United States, 77030
START Center for Cancer Care
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Gilead Sciences
California Institute for Regenerative Medicine (CIRM)
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02953782    
Other Study ID Numbers: 5F9004
First Posted: November 3, 2016    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Hu5F9-G4
Antineoplastic Agents, Immunological
Antineoplastic Agents