Study of Novel Treatment Combination Therapies in Participants with Head and Neck Squamous Cell Carcinoma.

Phase 2

Not yet recruiting

• Conditions: Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: Domvanalimab; Drug: Zimberelimab; Drug: Paclitaxel; Drug: Carboplatin

• Registration Number: NCT06727565
• Lead Sponsor: Gilead Sciences

Brief Summary

Master protocol: The main goal of this master clinical study is to evaluate the efficacy and safety of multiple novel combination therapies in participants with head and neck squamous cell carcinoma (HNSCC) in various substudies.

Detailed Description

This platform study will begin with a substudy targeting first-line (1L) recurrent or metastatic (r/m) HNSCC regardless of programmed cell death ligand 1 (PD-L1) expression status (Substudy-01), and new substudies may be added in the future targeting different study populations of HNSCC. All substudies evaluating additional drugs will be added in a staggered...

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-12
• Study Start: 2024-12
• Study First Submitted: 2024-12-09
• Study First Submitted QC: 2024-12-09
• Last Update Submitted: 2024-12-09
• Study First Posted: 2024-12-11
• Last Update Posted: 2024-12-11
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Histologically or cytologically confirmed r/m squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.
• No prior systemic therapy for r/m HNSCC. Individuals who had disease progression or recurrence more than 6 months after the last dose of curative intent systemic platinum-containing therapy for locoregionally advanced disease are eligible.
• At least 1 measurable lesion by computed tomography or magnetic resonance imaging that qualifies as a RECIST v1.1 target lesion at baseline.
• Have adequate tumor tissue samples preferably from lesions not irradiated prior to biopsy (acceptable from irradiated lesions if disease progression has been demonstrated in such lesions) to submit for central testing.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Known results from human papillomavirus (HPV) status test (p16 expression) for oropharyngeal carcinoma defined as p16 testing.

Key

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Exclusion Criteria

• Individuals with nasopharyngeal cancer (any histology), squamous cell carcinoma of unknown primary tumors, skin (cutaneous squamous cell carcinoma), paranasal sinuses, and salivary gland.

• Have disease that is suitable for any local therapies with curative intent.

• Individuals who had disease progression or recurrence within 6 months after the last dose of curative intent systemic platinum-containing therapy for locoregionally advanced disease.

• Have a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

• Have an active autoimmune disease that required systemic treatment in the past 2 years. (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.

• Prior treatment with any of the following within the specific time frame prior to the first dose of study drug:

  • Major surgery for any cause or significant traumatic injury within 4 weeks prior to the first dose of study drug. Individuals must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study drug.
  • Any noninvestigational anticancer therapy (chemotherapy, biologic therapy, targeted therapy, hormone therapy, or immunotherapy, etc) within 4 weeks prior to the first dose of study drug. Concurrent use for noncancer related condition (eg, hormone replacement therapy) is acceptable.
  • Any investigational drugs (drugs not marketed for any indication) within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug.
  • Radiation therapy within 2 weeks prior to the first dose of study drug. Individuals must have recovered to Grade ≤ 1 from all radiation-related toxicities, not requiring corticosteroid, and have not experienced radiation pneumonitis.

• Received prior treatment with any anti-PD-1/PD-L1, anti-TIGIT, or other immune checkpoint inhibitors.

• Currently receiving chronic systemic steroids (> 10 mg/day prednisone or its equivalent). Use of topical, inhalational, intranasal, intraocular steroids, and use as premedication for hypersensitivity reactions (eg, IV contrast allergy) are permitted.

• Any unresolved toxicity (Grade ≥ 2) per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 from prior anticancer therapy or surgical intervention, with the exception of alopecia, vitiligo, and the laboratory toxicities if the laboratory thresholds defined in the inclusion criteria are met. Individuals with Grade ≤ 2 neuropathy are eligible for this study.

• Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.

• Have known active central nervous system (CNS) metastases. Individuals with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastasis and are not requiring use of steroid for at least 14 days prior to the first dose of study drugs.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Substudy-01:Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy	Domvanalimab	Participants will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).
Substudy-01:Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy	Zimberelimab	Participants will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).
Substudy-01:Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy	Paclitaxel	Participants will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).
Substudy-01:Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy	Carboplatin	Participants will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).
Substudy-01: Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy	Zimberelimab	Participants will receive ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).
Substudy-01: Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy	Paclitaxel	Participants will receive ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).
Substudy-01: Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy	Carboplatin	Participants will receive ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).

Primary Outcome Measures

Name	Time	Method
Substudy-01: Objective response rate (ORR)	Up to 36 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 using investigator assessments.
Substudy-01: Progression-free survival (PFS)	Up to 36 months	PFS is defined as the time from the date of randomization until the first date of documented progressive disease (PD) or death from any cause, whichever occurs first, as measured by RECIST v1.1 using investigator assessments.

Secondary Outcome Measures

Name	Time	Method
Substudy-01: Duration of Response (DOR)	Up to 36 months	DOR is defined as the time from the date of the first documented response until the first date of documented PD or death from any cause, whichever occurs first, as measured by RECIST v1.1 using investigator assessments.
Substudy-01: Progression-Free Survival at 6 Months (PFS6)	Up to 36 months	PFS6 is defined as the proportion of participants alive and PD-free from date of randomization until 6 months as measured by RECIST v1.1 using investigator assessments.
Substudy-01: Overall Survival (OS)	Up to 36 months	OS is defined as the time from the date of randomization until the date of death from any cause.
Substudy-01: Overall Survival at 6 Months (OS6)	Up to 36 months	OS6 is defined as the proportion of participants alive at 6 months from the date of randomization, respectively.
Substudy-01: Overall Survival at 12 Months (OS12)	Up to 36 months	OS12 is defined as the proportion of participants alive at 12 months from the date of randomization, respectively.
Substudy-01: Disease Control Rate (DCR)	Up to 36 months	DCR is defined as the proportion of participants who achieve a CR, PR, or stable disease (SD) as measured by RECIST v1.1 using investigator assessments.
Substudy-01: Time to Progression (TTP)	Up to 36 months	TTP, defined as the time from randomization until the first date of documented PD as measured by RECIST v1.1 using investigator assessments
Substudy-01: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Related TEAEs	First dose date up to 24 months plus 100 days
Substudy-01: Percentage of Participants Experiencing Clinical Laboratory Abnormalities	First dose date up to 24 months plus 100 days