N/A

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Feb 2025 → 17 Feb 2026

Decision date (initial)

2024-12-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy of domvanalimab and zimberelimab in combination with chemotherapy vs zimberelimab in combination with chemotherapy

Secondary objectives 2

1. To assess the effect of domvanalimab and zimberelimab in combination with chemotherapy vs zimberelimab in combination with chemotherapy on: Duration of response (DOR). PFS rate at 6 months (PFS6). Overall survival (OS). OS rate at 6 months and 12 months (OS6 and OS12). Disease control rate (DCR). Time to progression (TTP).
2. To assess the safety of domvanalimab and zimberelimab in combination with chemotherapy vs zimberelimab in combination with chemotherapy

Conditions and MedDRA coding

Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants must be 18 years of age or older and able to understand and give written informed consent.
2. Histologically or cytologically confirmed r/m squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.
3. No prior systemic therapy for r/m HNSCC. Participants 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.
4. At least 1 measurable lesion by computed tomography or magnetic resonance imaging that qualifies as a RECIST v1.1 target lesion at baseline. Note: tumor lesions located in a previously irradiated field may be considered measurable if disease progression has been demonstrated in such lesions.
5. 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 of PD-L1 status by investigational for stratification at randomization (Cohort 1 only) and biomarker assessment. Archived tumor tissue samples that were obtained preferably within 24 months prior to the initial dosing (Cycle 1 Day 1) are acceptable but newly acquired samples at baseline are required if archived samples are not available. A fresh biopsy should be taken per standard-of-care practices and only if the attending physician deems it safe. Note: in Cohort 1, PD-L1 expression will be monitored as participant accrual occurs, and if there is a significant difference from the published prevalence, certain PD-L1 expression groups may be prioritized to enroll in the study. Prioritizing certain PD-L1 expression groups will not be implemented until the proper approvals from the Health Authorities have been obtained (IVDR authorization). Note: newly acquired samples at baseline are required (archival tissue samples can be additionally submitted) in Cohort 2.
6. Known results from HPV status test (p16 expression) for oropharyngeal carcinoma defined as p16 testing with immunohistochemistry (IHC) assay. HPV testing by polymerase chain reaction (PCR) and in situ hybridization (ISH) can be accepted. If local results by above methods are not available, a tumor tissue sample must be submitted to the designated central laboratory to be tested and p16 status is required prior to randomization. Note: in Cohort 1, documentation of HPV p16 status is required prior to randomization.

Exclusion criteria 11

1. Individuals with nasopharyngeal cancer (any histology), squamous cell carcinoma of unknown primary tumors, skin (cutaneous squamous cell carcinoma), paranasal sinuses, and salivary gland.
2. Have disease that is suitable for any local therapies with curative intent.
3. 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.
4. Have a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
5. 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.
6. 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 oxicities, not requiring corticosteroid, and have not experienced radiation pneumonitis.
7. Received prior treatment with any anti-PD-1/PD-L1, anti-TIGIT, or other immune checkpoint inhibitors.
8. 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.
9. 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.
10. Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
11. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Objective response rate (ORR), 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 [Time Frame: Up to 36 months]
2. Progression-free survival (PFS), 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 [Time Frame: Up to 36 months]

Secondary endpoints 8

1. DOR, defined as the time from the date of the first documented response until the first date of documented PD or death from any cause, whichever occurs first, as measured by RECIST v1.1 using investigator assessments. [Time Frame: Up to 36 months]
2. PFS6, defined as the proportion of participants alive and PD-free from date of randomization until 6 months as measured by RECIST v1.1 using investigator assessments. [Time Frame: Up to 36 months]
3. OS, defined as the time from the date of randomization until the date of death from any cause. [Time Frame: Up to 36 months]
4. OS6 and OS12, defined as the proportion of participants alive at 6 months and 12 months from the date of randomization, respectively. [Time Frame: Up to 36 months]
5. DCR, defined as the proportion of participants who achieve a CR, PR, or stable disease (SD) as measured by RECIST v1.1 using investigator assessments. [Time Frame: Up to 36 months]
6. TTP, defined as the time from randomization until the first date of documented PD as measured by RECIST v1.1 using investigator assessments. [Time Frame: Up to 36 months]
7. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Related TEAEs. [Time Frame: First dose date up to 24 months plus 100 days]
8. Percentage of Participants Experiencing Clinical Laboratory Abnormalities. [Time Frame: First dose date up to 24 months plus 100 days]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 5

Locations

3 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications