Clinical trial NCT02953782: Study of Magrolimab (Hu5F9-G4) in Combination With Cetuximab in Participants With Solid Tumors and Advanced Colorectal Cancer
Official title: A Phase 1b/2 Trial of Hu5F9-G4 in Combination With Cetuximab in Patients With Solid Tumors and Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Colorectal Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2016-11-03
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Dose Limiting Toxicities (DLT)
timeFrame: From first dose up to Day 28
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose date up to last dose date plus 30 days (maximum: 15.3 months)
measure: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: 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:
measure: Pharmacokinetic (PK) Parameter: Cmax of Magrolimab
timeFrame: 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)
measure: PK Parameter: Tmax of Magrolimab
timeFrame: 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)
measure: PK Parameter: AUClast of Magrolimab
timeFrame: 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)
measure: PK Parameter: AUCtau of Magrolimab
timeFrame: 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)
measure: Percentage of Participants With Anti-drug Antibodies (ADA)
timeFrame: Baseline; post-treatment (assessed continuously up to 30 days after last dose; maximum 15.3 months )
measure: Disease Control Rate (DCR) as Assessed by RECIST v1.1
timeFrame: From Screening until 38.89 months (assessed on Cycle 3 Day 1 then every 8 weeks from Cycle 5 onwards up to 38.89 months; 1 cycle = 4 weeks)
measure: Duration of Response (DOR) as Assessed by RECIST v1.1
timeFrame: From first objective response until documented PD (assessed on Cycle 3 Day 1 then every 8 weeks from Cycle 5 onwards up to 38.89 months; 1 cycle = 4 weeks)
measure: Progression Free Survival (PFS) as Assessed by RECIST v1.1
timeFrame: From first dose until documented PD/death (assessed on Cycle 3 Day 1 then every 8 weeks from Cycle 5 onwards up to 38.89 months; 1 cycle = 4 weeks)
measure: Overall Survival (OS)
timeFrame: From first dose until death (assessed on Cycle 3 Day 1 then every 8 weeks from Cycle 5 onwards up to 38.89 months; 1 cycle = 4 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Philadelphia
country: United States
facility: UPENN
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Md Anderson
state: Texas
city: San Antonio
country: United States
facility: START Center for Cancer Care
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: