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.
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.
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.
Parallel
GSK5764227
DrugGSK5764227 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.
Dostarlimab
DrugDostarlimab 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.
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.
Assess efficacy (e.g. Objective Response Rate, Progression-Free Survival, Overall Survival)
Assess efficacy (e.g. Objective Response Rate, Progression-Free Survival, Overall Survival) by RECIST 1.1
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
Safety includes incidence and severity of treatment emergent AEs, SAEs, AESIs, AEs leading to dose modification according to CTCAE v5.0. Vital signs, body weight, laboratory tests (hematology, clinical chemistry, urinalysis, cardiac function (Electrocardiogram) and Eastern Cooperative Oncology Group (ECOG) performance status changes.
To evaluate the PK of GSK5764227 monotherapy and in combination with dostarlimab.
Observed PK concentrations of GSK5764227 (conjugated antibody and small molecule payload) during the first 3 cycles. PK analyses assess drug exposure for GSK5764227 (monotherapy and with dostarlimab) and relate it to PD biomarkers, clinical efficacy (ORR, PFS, OS), and safety outcomes.
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University Health Network, Toronto
Lead sponsor
GlaxoSmithKline
Collaborator
