Evaluating new treatment combinations for head and neck cancer

A Phase 2 Platform Study of Novel Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma

This study is testing a new combination of treatments for people with advanced head and neck cancer to see if it works better than the current standard treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gilead Sciences (industry)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation, prednisone, domvanalimab, zimberelimab
• Locations: 25 sites (Saint Louis, Missouri and 24 other locations)
• Trial ID: NCT06727565 on ClinicalTrials.gov

What this trial studies

This clinical study aims to assess the efficacy and safety of novel combination therapies for patients with head and neck squamous cell carcinoma (HNSCC). It includes a master protocol with multiple substudies, starting with a focus on first-line treatment for recurrent or metastatic HNSCC. The primary comparison is between a combination of domvanalimab and zimberelimab with chemotherapy versus zimberelimab with chemotherapy alone. The study will enroll approximately 100 participants and may expand to include additional substudies targeting different populations within HNSCC.

Who should consider this trial

Good fit: Ideal candidates are individuals with recurrent or metastatic squamous cell carcinoma of the head and neck who have not received prior systemic therapy.

Not a fit: Patients with localized head and neck cancer that can be treated with local therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide new effective treatment options for patients with advanced head and neck cancer.

How similar studies have performed: Other studies have shown promise with combination therapies in similar cancer types, suggesting potential for success in this approach.

Eligibility criteria

Key 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 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.

Where this trial is running

Saint Louis, Missouri and 24 other locations

• Siteman Cancer Center — Saint Louis, Missouri, United States (RECRUITING)
• Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research — Nashville, Tennessee, United States (RECRUITING)
• The University of Texas, MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• Monash Health — Clayton, Victoria, Australia (RECRUITING)
• Alfred Health — Melbourne, Victoria, Australia (RECRUITING)
• ICON Cancer Center — Kurralta Park, Australia (RECRUITING)
• Westmead Hospital — Sydney, Australia (RECRUITING)
• Sichuan Cancer Hospital — Chengdu, China (RECRUITING)
• Zhejiang Cancer Hospital — Hangzhou, China (RECRUITING)
• Guangxi Medical University Cancer Hospital — Nanning, China (RECRUITING)
• Shanghai East Hospital — Shanghai, China (RECRUITING)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, China (RECRUITING)
• CHU de Bordeaux — Pessac, France (RECRUITING)
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milano, Italy (RECRUITING)
• Istituto Nazionale Tumori Fondazione G. Pascale — Napoli, Italy (RECRUITING)
• Sarawak General Hospital — Sarawak, Malaysia (RECRUITING)
• Hospital Universitario Virgen del Rocio — Sevilla, Spain (RECRUITING)
• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City, Taiwan (RECRUITING)
• Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital — Kaohsiung, Taiwan (RECRUITING)
• China Medical University Hospital — Taichung, Taiwan (RECRUITING)
• National Taiwan University Hospital — Taipei City, Taiwan (RECRUITING)
• Taipei Veterans General Hospital — Taipei City, Taiwan (RECRUITING)
• Chang Gung Memorial Hospital, Linkou — Taoyuan, Taiwan (RECRUITING)
• Barts Health NHS Foundation Trust — London, United Kingdom (RECRUITING)
• The Royal Marsden NHS Foundation Trust — London, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Gilead Clinical Study Information Center

Conditions: Head and Neck Squamous Cell Carcinoma