Colorectal Cancer, Solid Tumor
Conditions
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).
Interventions
DRUGMagrolimab
Administered intravenously
DRUGCetuximab
Administered intravenously
Sponsors
California Institute for Regenerative Medicine (CIRM)
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLT) | From first dose up to Day 28 | 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. |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | From first dose date up to last dose date plus 30 days (maximum: 15.3 months) | 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. |
| Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline; post-treatment (assessed continuously up to 30 days after last dose; maximum 15.3 months ) | Percentage of Participants With Positive ADA at any timepoint was reported. |
| Disease Control Rate (DCR) as Assessed by RECIST v1.1 | 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) | 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. |
| 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) | Cmax is defined as the maximum concentration of drug. |
| Progression Free Survival (PFS) as Assessed by RECIST v1.1 | 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) | 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. |
| Overall Survival (OS) | 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) | 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. |
| Duration of Response (DOR) as Assessed by RECIST v1.1 | 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) | 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. |
| 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) | Tmax is defined as the time (observed time point) of Cmax. |
| 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) | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United States. The first participant was screened on 02 November 2016. The last study visit occurred on 10 February 2020.
Pre-assignment details
105 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 Participants with solid tumor received 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 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, started on Day 1. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 6 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 Participants with solid tumor received 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, started on Day 1. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 3 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 Participants with solid tumor received 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, started on Day 1. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 9 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 Participants with solid tumor received 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, started on Day 1. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 8 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 Participants with solid tumor received 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 also received 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 started on Day 1 with weekly dose in Cycle 2 and bi-weekly dose in Cycle 3 onwards for magrolimab. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 6 |
| Phase 2 Cohort 1 (KRASwt): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 Participants with advanced CRC who were KRASwt and were refractory to anti-EGFRmAb therapy received 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 started on Day 1; Days 8 and 22 were removed from Cycle 2 onwards for magrolimab. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 16 |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 Participants with advanced CRC with KRASm who had progressed or were not candidates for oxaliplatin or irinotecan-based therapy received 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 started on Day 1; Days 8 and 22 were removed from Cycle 2 onwards for magrolimab. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 15 |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 Participants with advanced CRC with KRASm who had progressed or were not candidates for oxaliplatin or irinotecan-based therapy received 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 also received 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 started on Day 1; Days 8 and 22 were removed from Cycle 3 onwards for magrolimab. Each cycle consisted of 4 weeks (28 days). Cetuximab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until unacceptable toxicity, voluntary withdrawal, or documented PD. | 15 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1b (Maximum Duration: 14.3 Months) | Death | 5 | 2 | 6 | 6 | 4 | 0 | 0 | 0 |
| Phase 1b (Maximum Duration: 14.3 Months) | Discontinued by Sponsor | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 |
| Phase 1b (Maximum Duration: 14.3 Months) | Participant placed in hospice care | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Phase 1b (Maximum Duration: 14.3 Months) | Withdrawal by Subject | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 |
| Phase 2 (Maximum Duration: 11.1 Months) | Death | 0 | 0 | 0 | 0 | 0 | 14 | 11 | 8 |
| Phase 2 (Maximum Duration: 11.1 Months) | Discontinued by Sponsor | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 4 |
| Phase 2 (Maximum Duration: 11.1 Months) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Phase 2 (Maximum Duration: 11.1 Months) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | 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 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 6.72 | 68.6 years STANDARD_DEVIATION 11.39 | 57.3 years STANDARD_DEVIATION 7.05 | 52.4 years STANDARD_DEVIATION 10.97 | 63.6 years STANDARD_DEVIATION 9.5 | 59.7 years STANDARD_DEVIATION 14.38 | 58.9 years STANDARD_DEVIATION 14.41 | 57.4 years STANDARD_DEVIATION 5.8 | 58.9 years STANDARD_DEVIATION 11.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants | 8 Participants | 5 Participants | 12 Participants | 13 Participants | 11 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 3 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 7 Participants | 8 Participants | 6 Participants | 8 Participants | 10 Participants | 8 Participants | 55 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants | 8 Participants | 5 Participants | 27 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants | 6 Participants | 4 Participants | 10 Participants | 7 Participants | 10 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 9 | 8 / 10 | 30 / 36 | 14 / 20 | 3 / 3 |
| other Total, other adverse events | 9 / 9 | 10 / 10 | 36 / 36 | 20 / 20 | 3 / 3 |
| serious Total, serious adverse events | 3 / 9 | 6 / 10 | 10 / 36 | 5 / 20 | 1 / 3 |
Outcome results
Primary
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.
Time frame: 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)
Population: Participants in All Treated with available data were analyzed. Efficacy results were planned to be reported separately for all CRC participants with KRASwt and KRASm tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 6.3 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0.0 percentage of participants |
Primary
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.
Time frame: From first dose date up to last dose date plus 30 days (maximum: 15.3 months)
Population: All Treated included all participants who received at least 1 dose of any study drugs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Magrolimab Priming Dose Only | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
Primary
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.
Time frame: From first dose up to Day 28
Population: DLT Evaluable Analysis Set included participants who received at least 1 dose of any study drugs during Phase 1b if the participant either experienced a DLT any time during the DLT assessment period (the first 4 weeks of treatment) or completed at least 4 infusions of magrolimab and 2 infusions of cetuximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Percentage of Participants With Dose Limiting Toxicities (DLT) | 16.7 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Dose Limiting Toxicities (DLT) | 0.0 percentage of participants |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Dose Limiting Toxicities (DLT) | 0.0 percentage of participants |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Dose Limiting Toxicities (DLT) | 14.3 percentage of participants |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Dose Limiting Toxicities (DLT) | 0.0 percentage of participants |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Dose Limiting Toxicities (DLT) | 0.0 percentage of participants |
Secondary
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.
Time frame: 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)
Population: Participants in All Treated with available data were analyzed. Efficacy results were planned to be reported separately for all CRC participants with KRASwt and KRASm tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Disease Control Rate (DCR) as Assessed by RECIST v1.1 | 50.0 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Disease Control Rate (DCR) as Assessed by RECIST v1.1 | 38.1 percentage of participants |
Secondary
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.
Time frame: 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)
Population: Participants in All Treated with available data were analyzed. Efficacy results were planned to be reported separately for all CRC participants with KRASwt and KRASm tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Duration of Response (DOR) as Assessed by RECIST v1.1 | 9.7 months |
Secondary
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.
Time frame: 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)
Population: Participants in All Treated with available data were analyzed. Efficacy results were planned to be reported separately for all CRC participants with KRASwt and KRASm tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Overall Survival (OS) | 9.5 months |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Overall Survival (OS) | 7.6 months |
Secondary
Percentage of Participants With Anti-drug Antibodies (ADA)
Percentage of Participants With Positive ADA at any timepoint was reported.
Time frame: Baseline; post-treatment (assessed continuously up to 30 days after last dose; maximum 15.3 months )
Population: Immunogenicity Analysis Set included participants with at least one reported ADA result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 0.00 percentage of participants |
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 33.3 percentage of participants |
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 33.3 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 0.00 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 0.00 percentage of participants |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 0.00 percentage of participants |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 0.00 percentage of participants |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 0.00 percentage of participants |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 0.00 percentage of participants |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 0.00 percentage of participants |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 14.3 percentage of participants |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 14.3 percentage of participants |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 0.00 percentage of participants |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 0.00 percentage of participants |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 0.00 percentage of participants |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 12.5 percentage of participants |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 6.3 percentage of participants |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 6.3 percentage of participants |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 13.3 percentage of participants |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 13.3 percentage of participants |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 0.00 percentage of participants |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Baseline ADA | 0.00 percentage of participants |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Post-Treatment ADA | 0.00 percentage of participants |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Percentage of Participants With Anti-drug Antibodies (ADA) | Overall ADA | 0.00 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter: Cmax of Magrolimab
Cmax is defined as the maximum concentration of drug.
Time frame: 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)
Population: Participants in the PK Analysis Set (participants who received any amount of magrolimab with at least one detectable post-treatment serum concentration of magrolimab) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 209 μg/mL | Standard Deviation 82 |
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 312 μg/mL | Standard Deviation 121 |
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 1.04 μg/mL | Standard Deviation 0.769 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 230 μg/mL | Standard Deviation 54.6 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.629 μg/mL | Standard Deviation 0.437 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 352 μg/mL | Standard Deviation 68.4 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 728 μg/mL | Standard Deviation 207 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.662 μg/mL | Standard Deviation 0.374 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 455 μg/mL | Standard Deviation 105 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 558 μg/mL | Standard Deviation 168 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.432 μg/mL | Standard Deviation 0.173 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 982 μg/mL | Standard Deviation 182 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.517 μg/mL | Standard Deviation 0.311 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 1100 μg/mL | Standard Deviation 287 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 2140 μg/mL | Standard Deviation 590 |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.479 μg/mL | Standard Deviation 0.17 |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 513 μg/mL | Standard Deviation 148 |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.559 μg/mL | Standard Deviation 0.254 |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 616 μg/mL | Standard Deviation 121 |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 775 μg/mL | Standard Deviation 110 |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 901 μg/mL | Standard Deviation 131 |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 1790 μg/mL | Standard Deviation 49.5 |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | Pharmacokinetic (PK) Parameter: Cmax of Magrolimab | Day 1 (Cycle 1 Day 1) | 0.525 μg/mL | Standard Deviation 0.296 |
Secondary
PK Parameter: AUClast of Magrolimab
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time frame: 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)
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 29 (Cycle 2 Day 1) | 1420 day*μg/mL | Standard Deviation 711 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 8 (Cycle 1 Day 8) | 676 day*μg/mL | Standard Deviation 75.3 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 29 (Cycle 2 Day 1) | 1560 day*μg/mL | Standard Deviation 413 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 29 (Cycle 2 Day 1) | 3330 day*μg/mL | Standard Deviation 1270 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 8 (Cycle 1 Day 8) | 1530 day*μg/mL | Standard Deviation 513 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 29 (Cycle 2 Day 1) | 4480 day*μg/mL | Standard Deviation 1220 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 8 (Cycle 1 Day 8) | 2140 day*μg/mL | Standard Deviation 726 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 29 (Cycle 2 Day 1) | 7340 day*μg/mL | Standard Deviation 2380 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 8 (Cycle 1 Day 8) | 2920 day*μg/mL | Standard Deviation 600 |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUClast of Magrolimab | Day 8 (Cycle 1 Day 8) | 1930 day*μg/mL | — |
Secondary
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).
Time frame: 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)
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 29 (Cycle 2 Day 1) | 1640 day*μg/mL | Standard Deviation 604 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 29 (Cycle 2 Day 1) | 1560 day*μg/mL | Standard Deviation 413 |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 8 (Cycle 1 Day 8) | 676 day*μg/mL | Standard Deviation 75.3 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 8 (Cycle 1 Day 8) | 1630 day*μg/mL | Standard Deviation 649 |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 29 (Cycle 2 Day 1) | 3630 day*μg/mL | Standard Deviation 1040 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 8 (Cycle 1 Day 8) | 2140 day*μg/mL | Standard Deviation 726 |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 29 (Cycle 2 Day 1) | 4480 day*μg/mL | Standard Deviation 1220 |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 29 (Cycle 2 Day 1) | 8770 day*μg/mL | Standard Deviation 1120 |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: AUCtau of Magrolimab | Day 8 (Cycle 1 Day 8) | 1930 day*μg/mL | — |
Secondary
PK Parameter: Tmax of Magrolimab
Tmax is defined as the time (observed time point) of Cmax.
Time frame: 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)
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.10 days |
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.94 days |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.12 days |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.13 days |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.12 days |
| Phase 1b Cohort 3: Magrolimab 20 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.13 days |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.13 days |
| Phase 1b Cohort 4: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.14 days |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.13 days |
| Phase 1b Cohort 5: Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.12 days |
| Phase 2 Cohort 1 Safety Run-in: Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.12 days |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.13 days |
| Phase 2 Cohort 2 (KRASm): Magrolimab 30 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.14 days |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 29 (Cycle 2 Day 1) | 0.12 days |
| Phase 2 Cohort 3 (KRASm): Magrolimab 45 mg/kg + Cetuximab 250 mg/m^2 | PK Parameter: Tmax of Magrolimab | Day 8 (Cycle 1 Day 8) | 0.12 days |
Secondary
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.
Time frame: 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)
Population: Participants in All Treated with available data were analyzed. Efficacy results were planned to be reported separately for all CRC participants with KRASwt and KRASm tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Cohort 1: Magrolimab 10 mg/kg + Cetuximab 200 mg/m^2 | Progression Free Survival (PFS) as Assessed by RECIST v1.1 | 3.6 months |
| Phase 1b Cohort 2: Magrolimab 10 mg/kg + Cetuximab 250 mg/m^2 | Progression Free Survival (PFS) as Assessed by RECIST v1.1 | 1.9 months |