Study of Magrolimab Given Together With FOLFIRI/Bevacizumab (BEV) in Participants With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)

PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD) as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1), or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is 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. Kaplan-Meier (KM) estimates were used in outcome measure analysis.

Time frame: Up to 83.4 weeks

Population: Participants in the Randomized Cohorts in the Intent-to-treat Analysis Set were analyzed. Intent-to-treat Analysis Set included all participants who were randomized in the study.

DLT was defined as any, * Grade 3 or higher hematologic toxicity including, serious hemolytic anemia, grade 4 neutropenia lasting \> 7 days * An event meeting Hy's Law criteria: * Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (≥ 3 x ULN) and, * Treatment-emergent total bilirubin elevation (\> 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase \< 2 x ULN), and * No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases, hemolysis)) * Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT-assessment period * Grade 3 fatigue lasting \> 7 days * In the opinion of the investigator, the AE was at least possibly related to magrolimab

Time frame: First dose date up to 28 days

Population: Participants in DLT-Evaluable Analysis Set were analyzed. DLT-Evaluable Analysis Set was defined as all participants in Safety Run-in cohort who met one of the following criteria in the DLT-evaluable period (defined as the first 28 days):~* Participant experienced a DLT at any time after initiation of first infusion of magrolimab.~* Participant did not experience a DLT and completes at least 3 infusions of magrolimab and at least 2 doses of bevacizumab and FOLFIRI in Safety Run-in Cohort.

Treatment-emergent adverse events (TEAEs) were defined as any AE that begun on or after the date of first dose of study drug up to the date of last dose of study treatment plus 30 days or the day before initiation of subsequent anticancer therapy, whichever came first. An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily have a causal relationship with the treatment.

Time frame: First dose date up to last dose date (up to 36 weeks) plus 30 days

Population: Participants in the Safety Run-in Cohort in the Safety Analysis Set were analyzed. The Safety Analysis Set included all participants who took at least 1 dose of any study drug.

Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade after the date of first dose of study drug up to the date of last dose of study treatment plus 30 days or the day before initiation of subsequent anticancer therapy, whichever came first.

Time frame: First dose date up to last dose date (up to 36 weeks) plus 30 days

Population: Participants in the Safety Run-in Cohort in the Safety Analysis Set were analyzed.

The EQ-VAS recorded the participants' self-rated health on a vertical VAS, where the end points were labeled the best health you can imagine and the worst health you can imagine. The scale range from 0 to 100, where '100' rating denotes the best health and '0' rating denotes the worst health. The EQ-VAS is used as a quantitative measure of health outcome that reflects the participants' own judgment.

Time frame: Baseline, Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle is of 28 days)

Population: Participants in the Randomized Cohort in the Intent-to-treat Analysis Set with available data were analyzed.

EORTC QLQ-C30 is a quality of life (QOL) questionnaire for cancer participants, that has 30 items. 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, and financial difficulties). Scoring of the QLQ-C30 was performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicated a higher level of symptoms (i.e. a worse state of the participant).

Time frame: Baseline, Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle was of 28 days)

Population: Participants in the Randomized cohort in the Intent-to-treat Analysis Set with available data were analyzed. Data was collected until Cycle 8.

The FCSI was a set of brief, clinically relevant, colorectal cancer symptoms for assessing symptomatic response. It comprised the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions were combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items were scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items was transformed to a 0-100 scale, and the average for each of the 3 subscales was calculated; high scores illustrated an improved state.

Time frame: Baseline, Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle is of 28 days)

Population: Participants in the Randomized Cohort in the Intent-to-Treat Analysis Set with available data were analyzed.

DOR was defined as time from first documentation of CR or PR to the earliest date of documented disease progression as determined by investigator assessment, per RECIST V1.1, or death from any cause, whichever occurred first. PD was defined in outcome measure #4. CR and PR were defined in outcome measure #5. KM estimates were used in outcome measure analysis.

Time frame: Up to 83.4 weeks

Population: Participants in the Randomized Cohorts in the Intent-to-Treat Analysis Set with objective response were analyzed.

EQ-5D-5L was an instrument for use as a measure of health outcome. The EQ-5D-5L consisted of 2 sections: EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). EQ-5D comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Number of participants per category were reported.

Time frame: Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle is of 28 days)

Population: Participants in the Randomized Cohort in the Intent-to-treat Analysis Set with available data were analyzed.

ORR was defined as the percentage of participants who achieve complete response (CR) or partial response (PR) that was confirmed at least 4 weeks after initial documentation of response, as determined by investigator assessment per RECIST, Version 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.

Time frame: Up to 83.4 weeks

Population: Participants in the Randomized Cohorts in the Intent-to-Treat Analysis Set were analyzed.

OS was defined as time from date of randomization to death from any cause. KM estimates were used in outcome measure analysis.

Time frame: Up to 83.4 weeks

Population: Participants in the Randomized Cohort in the Intent-to-Treat Analysis Set were analyzed.

Time frame: Predose: Day 15, 29, 57, 113 and 169; Postdose: Day 57 (1 hour)

Population: Participants in the Pharmacokinetic (PK) Analysis Set with available data were analyzed. The PK Analysis Set was defined as all participants who received any amount of magrolimab and have at least 1 measurable posttreatment serum concentration of magrolimab.

Time frame: Up to 36 weeks

Population: Participants in the Immunogenicity Analysis Set with available data were analyzed. Immunogenicity Analysis Set included all participants who received any amount of magrolimab and had at least 1 evaluable anti-drug antibody test result.