A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 193
- 试验地点
- 87
- 主要终点
- Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
研究概览
简要总结
The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of the study drug, magrolimab in combination with other anticancer therapies in participants with head and neck squamous cell carcinoma (HNSCC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed metastatic or locally recurrent HNSCC that is considered incurable by local therapies.
- •Safety Run-in Cohort 1 and Phase 2 Cohorts 1
- •Should not have had prior systemic therapy administered in the recurrent or metastatic setting.
- •Eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx. Nasopharynx is not included.
- •HNSCC per protocol specified inclusion criteria regardless of PD-L1 status.
- •Safety Run-in Cohort 2 and Phase 2 Cohort 3
- •Histologically or cytologically confirmed locally advanced/mHNSCC regardless of PD-L1 status with at least 1 and no more than 2 lines of prior systemic anticancer therapy in the locally advanced/metastatic setting.
排除标准
- •Active central nervous system (CNS) disease (individuals with asymptomatic and stable, treated CNS lesions who have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks are not considered active).
- •History of (noninfectious) pneumonitis that required steroids or current pneumonitis.
- •Progressive disease within 6 months of completion of curatively intended treatment for locally advanced/mHNSCC.
- •Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable), and Phase 2 Cohorts 1 and 2
- •Prior treatment with any of the following:
- •Anti-programmed cell death protein 1 or anti-PD-L1 checkpoint inhibitors.
- •Anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitors.
- •Safety Run-in Cohort 2 and Phase 2 Cohort 3
- •Prior treatment with a taxane.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- pembrolizumab 200 mg on Day 1 of each cycle
- 5-fluorouracil (5-FU) 1000 mg/m^2/day Days 1-4 of each cycle (for up to 6 cycles)
- platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
干预措施: Magrolimab (Drug)
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- pembrolizumab 200 mg on Day 1 of each cycle
- 5-fluorouracil (5-FU) 1000 mg/m^2/day Days 1-4 of each cycle (for up to 6 cycles)
- platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
干预措施: Pembrolizumab (Drug)
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- pembrolizumab 200 mg on Day 1 of each cycle
- 5-fluorouracil (5-FU) 1000 mg/m^2/day Days 1-4 of each cycle (for up to 6 cycles)
- platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
干预措施: 5-FU (Drug)
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- pembrolizumab 200 mg on Day 1 of each cycle
- 5-fluorouracil (5-FU) 1000 mg/m^2/day Days 1-4 of each cycle (for up to 6 cycles)
- platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
干预措施: Cisplatin (Drug)
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- pembrolizumab 200 mg on Day 1 of each cycle
- 5-fluorouracil (5-FU) 1000 mg/m^2/day Days 1-4 of each cycle (for up to 6 cycles)
- platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
干预措施: Carboplatin (Drug)
Safety Run-in Cohort 2, Magrolimab + Docetaxel
Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- docetaxel 75 mg/m^2 on Day 1 of each cycle Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
干预措施: Magrolimab (Drug)
Safety Run-in Cohort 2, Magrolimab + Docetaxel
Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive the following:
- magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses
- docetaxel 75 mg/m^2 on Day 1 of each cycle Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
干预措施: Docetaxel (Drug)
Pre-expansion Safety Run-in Cohort, Magrolimab + Pembrolizumab
The pre-expansion safety run-in cohort may be conducted at the sponsor's discretion prior to the initiation of Phase 2 Cohort 2. Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days.
Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
干预措施: Magrolimab (Drug)
Pre-expansion Safety Run-in Cohort, Magrolimab + Pembrolizumab
The pre-expansion safety run-in cohort may be conducted at the sponsor's discretion prior to the initiation of Phase 2 Cohort 2. Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days.
Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
干预措施: Pembrolizumab (Drug)
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort
1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort
1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Pembrolizumab (Drug)
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort
1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: 5-FU (Drug)
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort
1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Cisplatin (Drug)
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort
1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Carboplatin (Drug)
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: 5-FU (Drug)
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Cisplatin (Drug)
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Carboplatin (Drug)
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5- FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5- FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: 5-FU (Drug)
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5- FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Cisplatin (Drug)
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5- FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Carboplatin (Drug)
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5- FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Zimberelimab (Drug)
Phase 2 Cohort 2, Magrolimab + Pembrolizumab
Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab at the RP2D determined in the Safety run-in cohort 1 and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 2, Magrolimab + Pembrolizumab
Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab at the RP2D determined in the Safety run-in cohort 1 and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days.
Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
干预措施: Pembrolizumab (Drug)
Phase 2 Cohort 3, Magrolimab + Docetaxel
Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive magrolimab at the RP2D determined in the Safety run-in cohort 2 and docetaxel 75 mg/m^2 on Day 1 of each cycle. Each cycle is 21 days.
Magrolimab and docetaxel will be continued until loss of clinical benefit, unacceptable toxicity, or death.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 3, Magrolimab + Docetaxel
Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive magrolimab at the RP2D determined in the Safety run-in cohort 2 and docetaxel 75 mg/m^2 on Day 1 of each cycle. Each cycle is 21 days.
Magrolimab and docetaxel will be continued until loss of clinical benefit, unacceptable toxicity, or death.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
时间窗: First dose date up to 21 days
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.
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities
时间窗: First dose date up to 73 weeks plus 30 days
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.
Phase 2 Cohort 1, Arms A and B: Progression-free Survival (PFS)
时间窗: Up to 129 weeks
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.
Phase 2 Cohort 3: Objective Response Rate (ORR)
时间窗: Up to 129 weeks
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.
次要结局
- Safety Run-in Cohort 1 and 2, Phase 2 Cohort 1 Arm A and Phase 2 Cohort 3: Serum Concentration of Magrolimab(Day 8 1-Hour Postdose; Days 15, 22, 43: Predose; Day 43 1-Hour Postdose; Day 71 1-Hour Postdose; Days 85,127, 190,197, 211, 253 Predose; Day 253 1-Hour Postdose)
- Safety Run-in Cohort 1 and 2, Phase 2 Cohort 1 Arm A, C and Phase 2 Cohort 3: Percentage of Participants Who Developed Antidrug Antibodies (ADAs) to Magrolimab(Up to end of treatment (up to approximately 73 weeks))
- Phase 2 Cohort 1, Arms B and C: Progression-free Survival (PFS)(Up to 129 weeks)
- Phase 2 Cohort 1, Arms A, B and C: Objective Response Rate (ORR)(Up to 129 weeks)
- Phase 2 Cohort 3: Progression-free Survival (PFS)(Up to 129 weeks)
- All Phase 2 Cohorts: Duration of Response (DOR)(Up to 129 weeks)
- All Phase 2 Cohorts: Overall Survival (OS)(Up to 129 weeks)
- Phase 2 Cohorts: Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) Score(Baseline, Week 3, Week 6, Week 9, Week 12, Week 15, Week 18, Week 21, Week 24, Week 27 and Week 90)
- Phase 2 Cohorts: Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life - Head and Neck Module (EORTC QLQ-H&N35)(Baseline, Week 3, Week 6, Week 9, Week 12, Week 15, Week 18, Week 21, Week 24, Week 27, and Week 90)
- Phase 2 Cohorts: Number of Participants With 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L) Score(Baseline, Week 3, Week 6, Week 9, Week 12, Week 15, Week 18, Week 21, Week 24, Week 27 and Week 90)
- Phase 2 Cohorts: Change From Baseline in the EuroQol Visual Analogue Scale (EQ-VAS) Score(Baseline, Week 3, Week 6, Week 9, Week 12, Week 15, Week 18, Week 21, Week 24, Week 27 and Week 90)