Study Details

OVERVIEW

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 (VELOCITY-HNSCC)

PROTOCOL 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.

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Head and Neck Squamous Cell Carcinoma

Gender

N/A

Date

February 2025 - August 2026

Study Type

INTERVENTIONAL

Study Phase

PHASE2

Product

Domvanalimab, Zimberelimab, Paclitaxel, Carboplatin

Eligibility Information

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.

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.

Locations

Locations (25)

Siteman Cancer Center

St Louis, Missouri, United States, 63110

Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

Nashville, Tennessee, United States, 37203

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States, 77030

Monash Health

Clayton, Victoria, Australia, 3168

Alfred Health

Melbourne, Victoria, Australia, 3004

ICON Cancer Center

Kurralta Park, Australia, 5037

Westmead Hospital

Sydney, Australia, 2145

Sichuan Cancer Hospital

Chengdu, China, 610040

Zhejiang Cancer Hospital

Hangzhou, China, 310005

Guangxi Medical University Cancer Hospital

Nanning, China, 530012

Shanghai East Hospital

Shanghai, China, 200120

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

Wuhan, China, 430030

CHU de Bordeaux

Pessac, France, 33604

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy, 20133

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy, 80131

Sarawak General Hospital

Sarawak, Malaysia, 93586

Hospital Universitario Virgen del Rocio

Seville, Spain, 41013

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan, 80756

Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan, 833

China Medical University Hospital

Taichung, Taiwan, 40402

National Taiwan University Hospital

Taipei, Taiwan, 100229

Taipei Veterans General Hospital

Taipei, Taiwan, 11217

Chang Gung Memorial Hospital, Linkou

Taoyuan District, Taiwan, 33308

Barts Health NHS Foundation Trust

London, United Kingdom, EC1A 7BE

The Royal Marsden NHS Foundation Trust

London, United Kingdom, SW10 9NH

Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status. (VELOCITY-HNSCC)