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

VELOCITY-HNSCC Substudy-01: A Phase 2 Study of Novel Combination Therapies in Participants With Previously Untreated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status

NCT06727565•Gilead Sciences

View on ClinicalTrials.gov

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.

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

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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.
•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.

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.
+2 more criteria

Locations (23)

Siteman Cancer Center

St Louis, Missouri, United States

Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

Nashville, Tennessee, United States

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Westmead Hospital

Sydney, New South Wales, Australia

ICON Cancer Center

Kurralta Park, South Australia, Australia

Monash Health

Clayton, Victoria, Australia

Alfred Health

Melbourne, Victoria, Australia

Sichuan Cancer Hospital

Chengdu, China

Zhejiang Cancer Hospital

Hangzhou, China

Guangxi Medical University Cancer Hospital

Nanning, China

Key Dates

Start Date

February 18, 2025

Primary Completion Date

August 1, 2026

Completion Date

August 1, 2026

Last Updated

March 2, 2026

Enrollment

100

ESTIMATED participants

Conditions

Head and Neck Squamous Cell Carcinoma

Interventions

Domvanalimab

DRUG

Zimberelimab

DRUG

Paclitaxel

DRUG

Carboplatin

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 2, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer

A Study to Test Whether Treatment With BI 770371 in Combination With Pembrolizumab With or Without Cetuximab Helps People With Head and Neck Cancer Compared With Pembrolizumab Alone

Dosing Study of Radiation Combined With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Cancer

Neoadjuvant Pembrolizumab and IO102-103 for Squamous Cell Carcinoma of the Head and Neck (SCCHN).

Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery