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

Last updated: May 9, 2025
Sponsor: Gilead Sciences
Overall Status: Active - Recruiting

Phase

2

Condition

Head And Neck Cancer

Lung Cancer

Squamous Cell Carcinoma

Treatment

Zimberelimab

Domvanalimab

Carboplatin

Clinical Study ID

NCT06727565
GS-US-699-7184
2024-513121-22
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Key Inclusion Criteria:

  • Histologically or cytologically confirmed r/m squamous cell carcinoma of the oralcavity, oropharynx, hypopharynx, and larynx that is considered incurable by localtherapies.

  • No prior systemic therapy for r/m HNSCC. Individuals who had disease progression orrecurrence more than 6 months after the last dose of curative intent systemicplatinum-containing therapy for locoregionally advanced disease are eligible.

  • At least 1 measurable lesion by computed tomography or magnetic resonance imagingthat qualifies as a RECIST v1.1 target lesion at baseline.

  • Have adequate tumor tissue samples preferably from lesions not irradiated prior tobiopsy (acceptable from irradiated lesions if disease progression has beendemonstrated 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) fororopharyngeal carcinoma defined as p16 testing.

Exclusion

Key Exclusion Criteria:

  • Individuals with nasopharyngeal cancer (any histology), squamous cell carcinoma ofunknown 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 lastdose of curative intent systemic platinum-containing therapy for locoregionallyadvanced disease.

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

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

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

  • Major surgery for any cause or significant traumatic injury within 4 weeksprior to the first dose of study drug. Individuals must have recoveredadequately from the toxicity and/or complications from the intervention priorto starting study drug.

  • Any noninvestigational anticancer therapy (chemotherapy, biologic therapy,targeted therapy, hormone therapy, or immunotherapy, etc) within 4 weeks priorto 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 4weeks or 5 half-lives (whichever is longer) prior to the first dose of studydrug.

  • Radiation therapy within 2 weeks prior to the first dose of study drug.Individuals must have recovered to Grade ≤ 1 from all radiation-relatedtoxicities, not requiring corticosteroid, and have not experienced radiationpneumonitis.

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

  • Currently receiving chronic systemic steroids (> 10 mg/day prednisone or itsequivalent). Use of topical, inhalational, intranasal, intraocular steroids, and useas premedication for hypersensitivity reactions (eg, IV contrast allergy) arepermitted.

  • Any unresolved toxicity (Grade ≥ 2) per National Cancer Institute Common TerminologyCriteria for Adverse Events v5.0 from prior anticancer therapy or surgicalintervention, with the exception of alopecia, vitiligo, and the laboratorytoxicities 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 3years prior to enrollment.

  • Have known active central nervous system (CNS) metastases. Individuals withpreviously treated brain metastases may participate provided they have stable CNSdisease for at least 4 weeks prior to enrollment and all neurologic symptoms havereturned to baseline, have no evidence of new or enlarging brain metastasis and arenot requiring use of steroid for at least 14 days prior to the first dose of studydrugs.

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

Study Design

Total Participants: 100
Treatment Group(s): 4
Primary Treatment: Zimberelimab
Phase: 2
Study Start date:
February 18, 2025
Estimated Completion Date:
August 31, 2026

Study 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 manner when relevant nonclinical and/or clinical data become available. Additional drugs may also be added to Substudy-01 in the future.

(GS-US-699-7184-01) 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.

Substudy-01 planned enrollment is approximately 100.

Connect with a study center

  • Monash Health

    Clayton, Victoria 3168
    Australia

    Active - Recruiting

  • Alfred Health

    Melbourne, Victoria 3004
    Australia

    Active - Recruiting

  • ICON Cancer Center

    Kurralta Park, 5037
    Australia

    Active - Recruiting

  • Westmead Hospital

    Sydney, 2145
    Australia

    Active - Recruiting

  • Sichuan Cancer Hospital

    Chengdu, 610040
    China

    Active - Recruiting

  • Zhejiang Cancer Hospital

    Hangzhou, 310005
    China

    Active - Recruiting

  • Guangxi Medical University Cancer Hospital

    Nanning, 530012
    China

    Active - Recruiting

  • Shanghai East Hospital

    Shanghai, 200120
    China

    Active - Recruiting

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

    Wuhan, 430030
    China

    Active - Recruiting

  • CHU de Bordeaux

    Pessac, 33604
    France

    Active - Recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milano, 20133
    Italy

    Active - Recruiting

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Napoli, 80131
    Italy

    Active - Recruiting

  • Sarawak General Hospital

    Sarawak, 93586
    Malaysia

    Active - Recruiting

  • Hospital Universitario Virgen del Rocio

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital

    Kaohsiung, 833
    Taiwan

    Active - Recruiting

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City, 80756
    Taiwan

    Active - Recruiting

  • China Medical University Hospital

    Taichung, 40402
    Taiwan

    Active - Recruiting

  • National Taiwan University Hospital

    Taipei City, 100229
    Taiwan

    Active - Recruiting

  • Taipei Veterans General Hospital

    Taipei City, 11217
    Taiwan

    Active - Recruiting

  • Chang Gung Memorial Hospital, Linkou

    Taoyuan, 33308
    Taiwan

    Active - Recruiting

  • Barts Health NHS Foundation Trust

    London, EC1A 7BE
    United Kingdom

    Active - Recruiting

  • The Royal Marsden NHS Foundation Trust

    London, SW10 9NH
    United Kingdom

    Active - Recruiting

  • Siteman Cancer Center

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

    Nashville, Tennessee 37203
    United States

    Active - Recruiting

  • The University of Texas, MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

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