Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status; Substudy-01

NCT06727565 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: GS-US-699-7184-012024-513121-22
• Study Type: interventional
• Target: 100
• Locations: 9 countries
• Sites: 23

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. Substudy-01 will evaluate the efficacy and safety of novel combination of treatment regimens, domvanalimab (DOM) and zimberelimab (ZIM) combined with chemotherapy vs ZIM combined with chemotherapy. The primary objective is to assess the efficacy of DOM and ZIM in combination with chemotherapy versus ZIM in combination with chemotherapy.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR)

  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.

  Up to 36 months

• Progression-free survival (PFS)

  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.

  Up to 36 months

Secondary Outcomes (9)

• Duration of Response (DOR)

  Up to 36 months

• Progression-Free Survival at 6 Months (PFS6)

  Up to 6 months

• Overall Survival (OS)

  Up to 36 months

• Overall Survival at 6 Months (OS6)

  Up to 6 months

• Overall Survival at 12 Months (OS12)

  Up to 12 months

Study Arms (2)

Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy

EXPERIMENTAL

Participants will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).

Drug: Domvanalimab; Drug: Zimberelimab; Drug: Paclitaxel; Drug: Carboplatin

Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy

EXPERIMENTAL

Participants will receive ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).

Drug: Zimberelimab; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Domvanalimab DRUG

Administered intravenously

Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy

Zimberelimab DRUG

Administered intravenously

Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy; Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy

Paclitaxel DRUG

Administered intravenously

Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy; Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy

Carboplatin DRUG

Administered intravenously

Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy; Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Gilead Sciences: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (23)

Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

Nashville, Tennessee, 37203, United States

Location

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

ICON Cancer Center

Kurralta Park, South Australia, 5037, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Sichuan Cancer Hospital

Chengdu, 610040, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310005, China

Location

Guangxi Medical University Cancer Hospital

Nanning, 530012, China

Location

Shanghai East Hospital

Shanghai, 200120, China

Location

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, 430030, China

Location

CHU de Bordeaux

Pessac, 33604, France

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131, Italy

Location

Sarawak General Hospital

Sarawak, 93586, Malaysia

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 40402, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan District, 33308, Taiwan

Location

Barts Health NHS Foundation Trust

London, EC1A 7BE, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW10 9NH, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

zimberelimab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 11, 2024
• Study Start: February 18, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4); MY (1); GB (2); US (3); ES (1); CN (5); AU (4); FR (1); IT (2)