Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status; Substudy-01
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Objective response rate (ORR) — Up to 36 months 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.
Progression-free survival (PFS) — Up to 36 months 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.
Trial sites (23)
Facility
City
Region
Status
Siteman Cancer Center
St Louis
Missouri
Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research
Nashville
Tennessee
The University of Texas, MD Anderson Cancer Center
Houston
Texas
Westmead Hospital
Sydney
New South Wales
ICON Cancer Center
Kurralta Park
South Australia
Monash Health
Clayton
Victoria
Alfred Health
Melbourne
Victoria
Sichuan Cancer Hospital
Chengdu
China
Zhejiang Cancer Hospital
Hangzhou
China
Guangxi Medical University Cancer Hospital
Nanning
China
Shanghai East Hospital
Shanghai
China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan
China
CHU de Bordeaux
Pessac
France
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples
Italy
Sarawak General Hospital
Sarawak
Malaysia
Hospital Universitario Virgen del Rocio
Seville
Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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