Clinical trial NCT06727565: Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma.
Official title: A Phase 2 Platform Study of Novel Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Arcus Biosciences, Inc.
First posted: 2024-12-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

(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.

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.

Primary outcomes:
measure: Substudy-01: Objective response rate (ORR)
timeFrame: Up to 36 months
measure: Substudy-01: Progression-free survival (PFS)
timeFrame: Up to 36 months
Secondary outcomes:
measure: Substudy-01: Duration of Response (DOR)
timeFrame: Up to 36 months
measure: Substudy-01: Progression-Free Survival at 6 Months (PFS6)
timeFrame: Up to 6 months
measure: Substudy-01: Overall Survival (OS)
timeFrame: Up to 36 months
measure: Substudy-01: Overall Survival at 6 Months (OS6)
timeFrame: Up to 6 months
measure: Substudy-01: Overall Survival at 12 Months (OS12)
timeFrame: Up to 12 months
measure: Substudy-01: Disease Control Rate (DCR)
timeFrame: Up to 36 months
measure: Substudy-01: Time to Progression (TTP)
timeFrame: Up to 36 months
measure: Substudy-01: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Related TEAEs
timeFrame: First dose date up to 24 months plus 100 days
measure: Substudy-01: Percentage of Participants Experiencing Clinical Laboratory Abnormalities
timeFrame: First dose date up to 24 months plus 100 days
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research
state: Tennessee
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Kurralta Park
country: Australia
facility: ICON Cancer Center
city: Sydney
country: Australia
facility: Westmead Hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Pessac
country: France
facility: CHU de Bordeaux
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Sarawak
country: Malaysia
facility: Sarawak General Hospital
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: London
country: United Kingdom
facility: Barts Health NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: