MedPath

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

Phase 2
Terminated
Conditions
Head and Neck Squamous Cell Carcinoma
Interventions
Registration Number
NCT04854499
Lead Sponsor
Gilead Sciences
Brief Summary

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 patients with head and neck squamous cell carcinoma (HNSCC).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
193
Inclusion Criteria
  • 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.

Key

Exclusion Criteria
  • 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + PlatinumPembrolizumabParticipants 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 * 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.
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum5-FUParticipants 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 * 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.
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + PlatinumCisplatinParticipants 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 * 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.
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + PlatinumCarboplatinParticipants 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 * 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.
Safety Run-in Cohort 2, Magrolimab + DocetaxelDocetaxelParticipants 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 * 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.
Pre-expansion Safety Run-in Cohort, Magrolimab + PembrolizumabPembrolizumabThe 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.
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)PembrolizumabParticipants 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.
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)5-FUParticipants 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.
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)CisplatinParticipants 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.
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)CarboplatinParticipants 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.
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)PembrolizumabParticipants 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.
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)5-FUParticipants 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.
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)CarboplatinParticipants 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.
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)CisplatinParticipants 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.
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)5-FUParticipants 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.
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)CisplatinParticipants 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.
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)ZimberelimabParticipants 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.
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)CarboplatinParticipants 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.
Phase 2 Cohort 2, Magrolimab + PembrolizumabPembrolizumabParticipants 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.
Phase 2 Cohort 3, Magrolimab + DocetaxelDocetaxelParticipants 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.
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + PlatinumMagrolimabParticipants 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 * 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.
Safety Run-in Cohort 2, Magrolimab + DocetaxelMagrolimabParticipants 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 * 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.
Pre-expansion Safety Run-in Cohort, Magrolimab + PembrolizumabMagrolimabThe 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.
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)MagrolimabParticipants 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.
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)MagrolimabParticipants 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.
Phase 2 Cohort 2, Magrolimab + PembrolizumabMagrolimabParticipants 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.
Phase 2 Cohort 3, Magrolimab + DocetaxelMagrolimabParticipants 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.
Primary Outcome Measures
NameTimeMethod
Safety Run-in Cohorts: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0First Dose up to 21 days
Phase 2 Cohorts 2 and 3: Objective Response Rate (ORR)Up to 9 months

ORR is defined as the proportion of participants who achieve 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.

Phase 2 Cohorts 1: Progression-free Survival (PFS)Up to 5 years

PFS is 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 occurs first.

Secondary Outcome Measures
NameTimeMethod
Safety Run-In and Phase 2 Cohorts: Serum Concentration of MagrolimabUp to end of treatment (approximately 24 months)
Safety Run-In and Phase 2 Cohorts: Percentage of Participants who Developed Antidrug Antibodies (ADAs) to MagrolimabUp to end of treatment (approximately 24 months)
Phase 2 Cohorts: Progression-free Survival (PFS)Up to 5 years

PFS is 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.

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) ScoreBaseline; up to 24 months

The EORTC QLQ-C30 questionnaire is a specific questionnaire for cancer, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is 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 indicate a higher level of symptoms (i.e. a worse state of the participant).

Phase 2 Cohorts: Overall Survival (OS)Up to 5 years

OS is defined as the time from the date of randomization (Phase 2 Cohorts 1) or time from the date of dose initiation (Phase 2 Cohorts 2 and 3) to death from any cause.

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; up to 24 months

The head \& neck cancer module is a 35-item questionnaire designed for use among a wide range of participants with head \& neck cancer, varying in disease stage and treatment modality. 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. Using a 4-point Likert scale, participants indicate the degree to which they have experienced symptoms. For all items and scales, high scores indicate more problems.

Phase 2 Cohorts: Change From Baseline in the 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)Baseline; up to 24 months

The EQ-5D-5L is a standard measure of health-related quality of life. The tool consists of the EQ-5D-5L descriptive part and the EQ visual analogue scale (VAS). The descriptive part comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each of these 5 dimensions has 5 levels (no problem, slight problems, moderate problems, severe problems, and extreme problems). Results for each of the 5 dimensions are combined into a 5-digit number to describe the participant's health state.

The EQ-VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating "the worst health you can imagine" and 100 indicating "the best health you can imagine." Higher scores of EQ VAS indicate better health.

Phase 2 Cohorts: Objective Response Rate (ORR)Up to 9 months

ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as determined by investigator assessment.

Phase 2 Cohorts: Duration of Response (DOR)Up to 5 years

DOR is 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.

Trial Locations

Locations (87)

UCLA Hematology/Oncology

🇺🇸

Los Angeles, California, United States

Memorial Healthcare System

🇺🇸

Hollywood, Florida, United States

Algemeen Ziekenhuis Klina

🇧🇪

Brasschaat, Belgium

Hospital de Braga

🇵🇹

Braga, Portugal

Avera Cancer Institute

🇺🇸

Sioux Falls, South Dakota, United States

Ironwood Cancer and Research Center

🇺🇸

Chandler, Arizona, United States

Torrance Memorial Physician Network - Cancer Care Associates

🇺🇸

Redondo Beach, California, United States

University Center and Blood Center,LLC.

🇺🇸

Athens, Georgia, United States

Ocala Oncology Center

🇺🇸

Ocala, Florida, United States

Virginia Piper Cancer Center (Alliant Health

🇺🇸

Minneapolis, Minnesota, United States

Washington University of Medicine- Siteman Cancer Center

🇺🇸

Saint Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital

🇺🇸

New York, New York, United States

Astera Cancer Care

🇺🇸

East Brunswick, New Jersey, United States

New York Cancer and Blood Specialists

🇺🇸

Port Jefferson Station, New York, United States

Sanford Roger Maris Cancer Center

🇺🇸

Fargo, North Dakota, United States

MD Anderson Cancer Center

🇪🇸

Madrid, Spain

Blacktown Hospital

🇦🇺

Westmead, New South Wales, Australia

Macquarie University

🇦🇺

Macquarie Park, New South Wales, Australia

University of the Sunshine Coast

🇦🇺

Sippy Downs, Queensland, Australia

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg

🇧🇪

Antwerpen, Belgium

Alfred Health

🇦🇺

Melbourne, Victoria, Australia

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

UZ Antwerpen

🇧🇪

Edegem, Belgium

AZ Sint-Maarten

🇧🇪

Mechelen, Belgium

Universitaire Ziekenhuis Leuven

🇧🇪

Leuven, Belgium

Institut Bergonie

🇫🇷

Bordeaux, France

CHU UCL Namur - Sainte-Elisabeth

🇧🇪

Namur, Belgium

Institut Curie

🇫🇷

Paris, France

Centre Georges François Leclerc

🇫🇷

Dijon, France

Centre Léon Bérard

🇫🇷

Lyon, France

Hopital de la Timone

🇫🇷

Marseille, France

Hopital Pitie-Salpetriere

🇫🇷

Paris, France

Civils de Lyon-Centre Hopitalier Lyon Sud

🇫🇷

Pierre-benite, France

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III

🇩🇪

Bonn, Germany

Institut Gustave Roussy

🇫🇷

Villejuif, France

Charite University Medicine

🇩🇪

Berlin, Germany

Hopital Foch

🇫🇷

Suresnes, France

Universitatsmedizin Gottingen

🇩🇪

GÃttingen, Germany

Kath. Marienkrankenhaus gGmbH

🇩🇪

Hamburg, Germany

Universitäres Krebszentrum Leipzig

🇩🇪

Leipzig, Germany

Queen Mary Hospital

🇭🇰

Hong Kong, Hong Kong

Azienda Ospedaliero - Universitaria Senese

🇮🇹

Siena, Italy

ASST degli Spedali Civili di Brescia

🇮🇹

Brescia, Italy

Princess Margaret Hospital

🇭🇰

Lai Chi Kok, Hong Kong

Ospedale San Luca Luca

🇮🇹

Lucca, Italy

Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy

🇵🇱

Bydgoszcz, Poland

Wielkopolskie Centrum Onkologii im. Marii Sklodowskiej-Curie, Oddzial Onkologii Klinicznej i Immunookologii z Poddoddzialem Dziennym i Izba Przyjec

🇵🇱

Poznan, Poland

Wojewodzki Szpital Specjalistyczny w Siedlcach

🇵🇱

Siedlce, Poland

Narodowy Instytut Onkologii im. M. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Glowy i Szyi

🇵🇱

Warsaw, Poland

Centro Hospitalar do Algarve

🇵🇹

Faro, Portugal

Centro Hospitalar Universitario do Porto

🇵🇹

Porto, Portugal

Instituto Portugues de Oncologia Do Porto Francisco Gentil,E.P.E.

🇵🇹

Porto, Portugal

Hospital De La Santa Creu I Sant Pau

🇪🇸

Barcelona, Spain

Hospital del Mar

🇪🇸

Barcelona, Spain

Royal Marsden NHS Foundation Trust, Royal Marsden - Sutton

🇬🇧

London, United Kingdom

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Lancaster General Hospital

🇺🇸

Lancaster, Pennsylvania, United States

Musgrove Park Hospital

🇬🇧

Taunton, United Kingdom

City of Hope

🇺🇸

Duarte, California, United States

Stanford Cancer Institute

🇺🇸

Palo Alto, California, United States

Indiana University Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

OU Health Stephenson Cancer Center

🇺🇸

Oklahoma City, Oklahoma, United States

Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

St. Vincent's Hospital Sydney

🇦🇺

Darlinghurst, New South Wales, Australia

Cairns Hospital

🇦🇺

Cairns, Queensland, Australia

Centre Hospitalizer De L'Ardenne

🇧🇪

Libramont-Chevigny, Belgium

Centre de Lutte Contre le Cancer (CLCC) - Centre Antoine Lacassagne (CAL) - Site Est

🇫🇷

Nice, France

Technische Universitat Munchen (TUM) - Klinikum Rechts der Isar

🇩🇪

Munich, Germany

Azienda Ospedaliero - Universitaria di Bologna - IRCCS

🇮🇹

Bologna, Italy

Azienda Ospedaliero-Universitaria di Modena - Policlinico

🇮🇹

Modena, Italy

Arcispedale Santa Maria Nuova

🇮🇹

Reggio Emilia, Italy

Fondazione IRCCS Istituto Nazionale Tumori Milano

🇮🇹

Milan, Italy

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie, Panstwowy Instytut Badawczy, Oddzial x Gliwicach

🇵🇱

Gliwice, Poland

Hospital CUF Descobertas

🇵🇹

Lisboa, Portugal

Unidade Local de Saude de Matosinhos EPE - Hospital Pedro Hispano SA

🇵🇹

Matosinhos, Portugal

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

Hospital Universitario de Jaen

🇪🇸

Jaen, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Regional Universitario de Malaga

🇪🇸

Malaga, Spain

Clinica Universidad de Navarra

🇪🇸

Pamplona, Spain

Hospital Universitari i Politecnic La Fe

🇪🇸

Valencia, Spain

Providence Medical Foundation

🇺🇸

Santa Rosa, California, United States

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Clínico Universitario de Valencia

🇪🇸

Valencia, Spain

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

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