Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Becotatug Vedotin, PD-1 Inhibitor, EGFR-Targeted Antibody-Drug Conjugate, Objective Response Rate
Brief summary
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.
Interventions
DRUGBecotatug Vedotin Combined with PD-1 Inhibitor
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.
Sponsors
Feng Liu
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years. * Primary tumor of head and neck squamous cell carcinoma, excluding nasopharyngeal carcinoma. * Disease assessed as not suitable for complete surgical resection, or the participant refuses surgery despite being considered technically eligible for surgery. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * No obvious contraindications to immunotherapy, radiotherapy, or chemotherapy. * Adequate major organ function, defined as follows: * Hematologic function: white blood cell count (WBC) ≥4.0 × 10\^9/L, absolute neutrophil count (ANC) ≥1.5 × 10\^9/L, platelet count (PLT) ≥100 × 10\^9/L, and hemoglobin (Hb) ≥90 g/L without blood transfusion, blood products, G-CSF, or other hematopoietic growth factors within 14 days before testing. * Biochemical function: serum albumin ≥3.0 g/dL (30 g/L), total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, and blood urea nitrogen (BUN) and serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min calculated by the Cockcroft-Gault formula. * Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN. For participants receiving anticoagulant therapy, PT must be within the intended therapeutic range of the anticoagulant. * Women of childbearing potential must use reliable contraception, have a negative pregnancy test within 7 days before enrollment, and agree to use effective contraception during the study and for 2 months after the last dose of anti-PD-1 antibody. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 2 months after the last dose of anti-PD-1 antibody. * The participant voluntarily agrees to participate in the study, signs the informed consent form, and is willing and able to comply with study visits and follow-up.
Exclusion criteria
* Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection; active hepatitis B infection, defined as HBV-DNA ≥10\^4 copies/mL; or hepatitis C infection, defined as positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay. * Known allergy to the study drug or any of its excipients, or a history of severe hypersensitivity reaction to other monoclonal antibodies. * Any of the following within 6 months before the first dose of study treatment: myocardial infarction, severe or unstable angina, New York Heart Association (NYHA) class II or higher heart failure, or symptomatic congestive heart failure. * Receipt of a live vaccine within 4 weeks before the first dose of study treatment. Inactivated injectable vaccines for seasonal influenza are permitted, but intranasal live attenuated influenza vaccines are not permitted. * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. * Known history of psychotropic drug abuse or illicit drug use. * Pregnant or breastfeeding women. * Diagnosis of any other malignancy within 5 years before study entry, except for locally treated and cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma. * Any other serious physical or psychiatric illness or laboratory abnormality that may increase the risk of study participation, interfere with study results, or make the participant unsuitable for this study in the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From enrollment to disease progression or death from any cause, up to 2 years. | Progression-free survival is defined as the time from enrollment to the first documented disease progression or death from any cause, whichever occurs first. |
| 1-Year and 2-Year Progression-Free Survival Rate | At 1 year and 2 years after enrollment. | 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. |
| 1-Year and 2-Year Overall Survival Rate | At 1 year and 2 years after enrollment. | 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. |
| Duration of Response (DoR) | From the first documented CR or PR to disease progression or death from any cause, up to 2 years. | 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. |
| Disease Control Rate (DCR) | 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. | 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. |
| Incidence and Severity of Adverse Events | From signing informed consent to 90 days after the last dose of study treatment. | 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. |
Outcome results
None listed