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Solid TumorPhase 1/2NCT02953782

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

A Phase 1/2 study testing Magrolimab and Cetuximab in people with Solid Tumor and Colorectal Cancer, run by Gilead Sciences at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Colorectal Cancer
What is being tested?
Magrolimab and Cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
8 sitesUnited States
Study dates
2 Nov 2016to 10 Feb 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Wayne State University

    Detroit, Michigan, 48201

  • START Midwest

    Grand Rapids, Michigan, 49503

  • Md Anderson

    Houston, Texas, 77030

  • UCLA

    Los Angeles, California, 90404

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Stanford University

    Palo Alto, California, 94305-5757

  • UPENN

    Philadelphia, Pennsylvania, 19104

  • START Center for Cancer Care

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase 1b/2 Trial of Hu5F9-G4 in Combination With Cetuximab in Patients With Solid Tumors and Advanced Colorectal Cancer

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).

Being tested
Magrolimab, Cetuximab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MagrolimabDrug

    Also called Hu5F9-G4

    Administered intravenously

  • CetuximabDrug

    Also called ERBITUX®

    Administered intravenously

Study groups in NCT02953782
Study groupRoleWhat they receive
Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2ExperimentalParticipants 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).
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 2 Cohort 1 (KRASwt): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab
Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From first dose up to Day 28

  2. 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.

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

  3. 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.

    Measured: 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)

  1. Pharmacokinetic (PK) Parameter: Cmax of Magrolimab

    Cmax is defined as the maximum concentration of drug.

    Measured: 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)

  2. PK Parameter: Tmax of Magrolimab

    Tmax is defined as the time (observed time point) of Cmax.

    Measured: 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)

  3. PK Parameter: AUClast of Magrolimab

    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

    Measured: 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)

  4. PK Parameter: AUCtau of Magrolimab

    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

    Measured: 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)

  5. Percentage of Participants With Anti-drug Antibodies (ADA)

    Percentage of Participants With Positive ADA at any timepoint was reported.

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

  6. Disease Control Rate (DCR) as Assessed by RECIST v1.1

    DCR was defined as the percentage of participants with disease control which consisted of CR+PR+SD. CR: Disappearance of all target lesions. 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. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters measured while on study. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions.

    Measured: 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)

  7. Duration of Response (DOR) as Assessed by RECIST v1.1

    DOR was measured from when the first (objective) response was met (i.e., CR or PR) until the first date of objectively documented PD. Participants who did not have objectively PD was censored at their last documented progression-free date. CR: Disappearance of all target lesions. 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. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Kaplan Meier estimate was used for analysis.

    Measured: 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)

  8. Progression Free Survival (PFS) as Assessed by RECIST v1.1

    PFS was measured from first dose until the first date of objectively documented PD or death. Participants who did not have objectively documented PD and not died was censored at their last documented progression-free date. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Kaplan Meier estimate was used for analysis.

    Measured: 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)

  9. Overall Survival (OS)

    OS was measured from first dose until death. Participants who did not die were censored at their last known alive date. Kaplan Meier estimate was used for analysis.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2016 (estimated)
  2. Study start2 Nov 2016
  3. Primary completion10 Feb 2020
  4. Study completion10 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02953782
Sponsor's protocol ID
5F9004
Status last verified
Feb 2021
First submitted
1 Nov 2016
Last updated
1 Mar 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Magrolimab and Cetuximab in people with Solid Tumor and Colorectal Cancer, run by Gilead Sciences at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Dose Limiting Toxicities (DLT) (time frame: From first dose up to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02953782.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2021.

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