Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma

PFS was defined as the time from the date of randomization until the earliest date of documented disease progression, as assessed by investigator assessment, or death from any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included 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. (Note: the appearance of one or more new lesions is also considered progression). Kaplan-Meier (KM) estimates were used in outcome measure analysis.

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 1, Arms A and B in the ITT analysis set were analyzed.

ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as determined by investigator assessment. CR is 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 is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 3 in the mITT Analysis Set with available data were analyzed.

A DLT was defined as any Grade 3 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity that had worsened in severity from pretreatment baseline during the DLT assessment period and, in the opinion of the investigator, the AE was related to magrolimab and the relationship of the AE with the combination partner regimen can be ruled out.

Time frame: First dose date up to 21 days

Population: DLT Evaluable Analysis Set was defined as all participants in the safety run-in evaluations who meet either of the following criteria during the DLT assessment period: The participants experienced a DLT at any time after initiation of the first infusion of magrolimab. The participant didn't experience a DLT and completed at least 2 infusions of magrolimab and at least 1 dose of pembrolizumab, platinum, and 5-FU for Safety Run-in Cohort 1; at least 1 dose of docetaxel for Safety Run-in Cohort 2.

Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point up to and including last dose date of study drug plus 30 days (or last dose date of zimberelimab plus 90 days) and prior to the day of initiation of subsequent anti-cancer therapy.

Time frame: First dose date up to 73 weeks plus 30 days

Population: Safety Run-in Cohorts 1 and 2: The Safety Analysis Set included all participants who took at least 1 dose of any study drug.

DOR was defined as the time from first documentation of CR or PR to the earliest date of documented disease progression or death from any cause, whichever occurs first. Disease progression is defined in OM#2 and CR and PR are defined in OM#3.

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 1, Arms A, B and C in the ITT and participants in Phase 2 Cohort 3 in the mITT analysis set who achieved overall response were analyzed.

OS was defined as the time from the date of randomization (Phase 2 Cohorts 1) or time from the date of dose initiation (Phase 2) to death from any cause. KM estimates were used in outcome measure analysis.

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 1, Arms A, B and C in the ITT and participants in Phase 2 Cohort 3 in the mITT analysis set were analyzed.

ORR was defined as the percentage of participants who achieved a CR or PR as determined by investigator assessment. CR and PR are defined in OM#3.

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 1, Arms A, B and C in the ITT Analysis Set were analyzed.

PFS was defined as the time from the date of randomization (Phase 2 Cohorts 1) or date of dose initiation (Phase 2 Cohorts 2 and 3) until the earliest date of documented disease progression as determined by investigator assessment per RECIST, version 1.1, or death from any cause, whichever occurs first. Disease progression is defined in OM#2. KM estimates were used in outcome measure analysis.

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 1 Arms B and C in the ITT Analysis Set were analyzed.

PFS was defined as the time from the date of dose initiation (Phase 2 Cohort 3) until the earliest date of documented disease progression as determined by investigator assessment per RECIST, version 1.1, or death from any cause, whichever occurs first. Disease progression is defined in OM#2. KM estimates were used in outcome measure analysis

Time frame: Up to 129 weeks

Population: Participants in Phase 2 Cohort 3 in the mITT Analysis Set were analyzed.

The H&N35 is a 35-item questionnaire for participants with H&N cancer. It includes 7 multi-item scales that assess pain (4 items), swallowing (4 items), senses (2 items), speech (3 items), social eating (4 items), social contact (5 items), and sexuality (2 items). There are also 11 single items: teeth, opening mouth, dry mouth, sticky saliva, coughing, felt ill, pain killers, nutritional supplements, feeding tube, weight loss, weight gain. All symptoms scales, scores were transformed in range of 0 to 100, where higher scores indicated more severe symptoms. A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 3, Week 6, Week 9, Week 12, Week 15, Week 18, Week 21, Week 24, Week 27, and Week 90

Population: Phase 2 Cohort 1: Participants in the Intent-to-Treat Analysis Set with available data were analyzed. Phase 2 Cohort 3: Participants in the Modified 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, Week 3, Week 6, Week 9, Week 12, Week 15, Week 18, Week 21, Week 24, Week 27 and Week 90

Population: Phase 2 Cohort 1: Participants in the Intent to Treat Analysis Set with available data were analyzed. Phase 2 Cohort 3: Participants in the Modified Intent-to-Treat analysis set with available data were analyzed.