A Comprehensive Multiomic Biomarker Evaluation Across Two Single-arm Cohorts to Elucidate Mechanisms of Response and Resistance in Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC)

NCT07408063 | Recruiting Phase 2 DMC

• 1 other identifier: BeeHive
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The BeeHive study is an investigator-initiated, single center, open-label phase II clinical trial that is designed to conduct a comprehensive multiomic biomarker evaluation across two single-arm cohorts to elucidate mechanisms of response and resistance in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). It is anticipated that about 20 patients will be enrolled in Cohort A and an additional of 10 patients will be enrolled in Cohort B.

Conditions

Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Determine molecular and immune biomarkers on pre and post-treatment tumor biopsies and longitudinal ctDNA kinetics as biomarkers for response or resistance to GSK5764227 and to GSK5764227 plus dostarlimab

  Find biomarkers (biopsy + ctDNA) linked to response/resistance to GSK5764227 with or without dostarlimab.

  3 years

Secondary Outcomes (3)

• Assess efficacy (e.g. Objective Response Rate, Progression-Free Survival, Overall Survival)

  3 years

• Determine safety and adverse event profiles of GSK5764227 in second- or third-line R/M HNSCC setting; and GSK5764227 plus dostarlimab in first-line R/M HNSCC setting

  3 years

• To evaluate the PK of GSK5764227 monotherapy and in combination with dostarlimab.

  3 years

Study Arms (2)

Arm A - GSK5764227

EXPERIMENTAL

All participants will receive GSK5764227 monotherapy at a starting dose of 8 mg/kg intravenously every 3 week (IV Q3W) in a 21-day treatment cycle.

Drug: GSK5764227

Arm B - GSK5764227 + Dostarlimab

EXPERIMENTAL

All participants will receive a combination of GSK5764227 (8 mg/kg IV Q3W) and dostarlimab (500 mg IV Q3W).

Drug: GSK5764227; Drug: Dostarlimab

Interventions

GSK5764227 DRUG

GSK5764227 is a new kind of drug known as an antibody drug conjugate (ADC). GSK5764227 works by recognizing and attaching to a substance known as B7-H3 that is found on the surface of certain tumor cells. Once GSK5764227 binds to B7-H3, it enters the tumor cell and releases a chemotherapy-type drug (known as GSK5757810) which has been shown to damage and kill tumor cells.

Arm A - GSK5764227; Arm B - GSK5764227 + Dostarlimab

Dostarlimab DRUG

Dostarlimab belongs to a class of drugs called PD-1 inhibitors that use your own immune system to treat cancer (immunotherapy). Dostarlimab is designed to help your immune system by attaching to a protein called PD-1 and stopping one of the signals that keeps your immune system from recognizing the cancer. This may help your immune system attack and destroy the cancer cells. Dostarlimab is approved in some countries to treat patients with endometrial cancer (cancer of the uterus) that is advanced or has relapsed. It is also approved in the United States for all solid cancers that have a particular tumor genetic characteristic and have worsened during or after previous treatment. Dostarlimab has not yet been approved by Health Canada to treat head and neck cancer.

Arm B - GSK5764227 + Dostarlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• At least 18 years old at the time of signing Informed Consent Form (ICF).
• Histologically or cytologically confirmed Head and Neck Squamous Cell Carcinoma (HNSCC) with evidence of metastatic or locally recurrent/advanced disease not amenable to curative local therapy (surgery or radiation). Eligible primary tumor locations include oral cavity, oropharynx (p16 positive or negative), hypopharynx and larynx. Patients with unknown primary HNSCC, SCC of nasopharynx or paranasal sinuses are excluded.
• For oropharyngeal cancer, documented Human Papillomavirus (HPV) status (p16 Immunohistochemistry (IHC) or HPV DNA/RNA) is required.
• At least one measurable lesion per RECIST v1.1
• ECOG performance status of 0 or 1.
• Life expectancy greater than 12 weeks.
• Cohort-Specific Criteria:
• Cohort A: R/M HNSCC in the second- or third-line setting, pretreated with an Immune Checkpoint Inhibitor (ICI) and progressed on platinum-based therapy in the R/M setting.
• Cohort B: R/M HNSCC in the first-line setting, systemic therapy-naïve in the R/M setting.
• Willingness and ability to undergo both a newly obtained, image-guided or surgical tumor biopsy during the screening period and a mandatory on-treatment tumor biopsy.
• No evidence of past or active hepatitis B infection, w/exception
• No evidence of active hepatitis C infection. Patients with undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) test are eligible.
• Participants must have no known history of HIV infection. HIV-1/2 testing is only required for patients with known risk factors.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other protocol requirements.

You may not qualify if:

• Participants with non-squamous histologies (e.g., adenocarcinoma, salivary gland carcinomas, and sarcomas) or HNSCC arising from the nasopharynx or paranasal sinuses are excluded. Participants with unknown primary tumors (even if squamous histology is confirmed) are also excluded.
• Has ongoing adverse reaction(s) from prior therapy that have not recovered to ≤Grade 1 or to the baseline status preceding prior therapy (excluding, for example, alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy), or that the Investigator, with the agreement of the Study PI, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• Any participation in another investigational study within 4 weeks prior to screening.
• Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
• Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
• \- For dostarlimab: Patients requiring chronic systemic immunosuppressive therapy within 30 days prior to first dose are excluded, except for those receiving low-dose corticosteroids (≤10 mg/day prednisone equivalent), inhaled/topical steroids, or physiological replacement therapy.
• Serious arteriovenous thromboembolic events (such as deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to the first dose (w/exceptions)
• Evidence of brain metastasis unless all the following criteria are met:
• Asymptomatic.
• Medically stable for at least 4 weeks prior to initial dosing.
• No steroid treatment required for at least 2 weeks prior to initial dosing.
• No imaging evidence of severe edema located around the tumor lesion.
• Also excluded are untreated progression due to brain metastasis during or after the last treatment prior to screening, evidence of meningeal/brainstem metastasis, or evidence of spinal cord compression (detected by radiographic examination, symptomatic or not).
• History of another primary solid tumor except for the following:
• Solid tumors that have been cured and inactive for ≥2 years before enrollment and at very low risk of recurrence.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Lillian Siu, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lillian Siu, MD

CONTACT

416-946-4501; tip@uhn.ca

Minge Xu

CONTACT

416-946-4501; minge.xu@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2026
• First Posted: February 12, 2026
• Study Start: April 27, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): March 1, 2031
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)