This is a prospective, open-label, non-randomized, two-cohort, single-arm Phase 2 study in adults with unresectable or recurrent/metastatic head and neck squamous cell carcinoma, excluding nasopharyngeal carcinoma. The study will evaluate the efficacy and safety of Becotatug vedotin, an EGFR-targeted antibody-drug conjugate, in combination with an investigator-selected PD-1 inhibitor. Participants will enter one of two cohorts based on prior treatment: those who have not received prior systemic treatment for unresectable or recurrent/metastatic disease, and those who have received at least one prior line of treatment. Becotatug vedotin will be given once every 21 days with the PD-1 inhibitor. Treatment may continue until disease progression, unacceptable side effects, withdrawal of consent, death, or other protocol-defined reasons. The main purpose is to assess objective response rate, defined as the percentage of participants whose tumors have a complete or partial response. Other outcomes include safety, tolerability, progression-free survival, overall survival, disease control rate, and duration of response.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Becotatug vedotin will be administered at 2.0 mg/kg by intravenous infusion once every 3 weeks in combination with an investigator-selected PD-1 inhibitor. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, death, or other protocol-defined reasons for discontinuation.
Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by investigators according to RECIST v1.1. ORR will be evaluated separately in each cohort.
Time frame: From enrollment until disease progression, death, withdrawal of consent, start of new anti-cancer therapy, loss to follow-up, or end of study, up to 2 years.
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from enrollment to the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From enrollment to disease progression or death from any cause, up to 2 years.
1-Year and 2-Year Progression-Free Survival Rate
The 1-year and 2-year progression-free survival rates are defined as the percentage of participants who remain alive and free of disease progression at 1 year and 2 years after enrollment.
Time frame: At 1 year and 2 years after enrollment.
1-Year and 2-Year Overall Survival Rate
The 1-year and 2-year overall survival rates are defined as the percentage of participants who remain alive at 1 year and 2 years after enrollment.
Time frame: At 1 year and 2 years after enrollment.
Duration of Response (DoR)
Duration of response is defined as the time from the first documented CR or PR to the first documented disease progression or death from any cause, whichever occurs first. This measure will be evaluated in participants who achieve CR or PR.
Time frame: From the first documented CR or PR to disease progression or death from any cause, up to 2 years.
Disease Control Rate (DCR)
Disease control rate is defined as the percentage of participants who achieve CR, PR, or stable disease (SD) as assessed by investigators according to RECIST v1.1. DCR will be evaluated separately in each cohort.
Time frame: From enrollment until disease progression, death, withdrawal of consent, start of new anti-cancer therapy, loss to follow-up, or end of study, up to 2 years.
Incidence and Severity of Adverse Events
Adverse events (AEs), serious adverse events (SAEs), immune-related adverse events, adverse events of special interest, infusion-related reactions, laboratory abnormalities, vital signs, physical examination findings, electrocardiogram findings, and echocardiography findings will be evaluated and summarized by severity, relationship to study treatment, action taken, and outcome. AEs will be graded according to NCI-CTCAE v5.0 and coded using MedDRA.
Time frame: From signing informed consent to 90 days after the last dose of study treatment.
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