Pucotenlimab Combined With Becotatug Vedotin in Advanced Cutaneous Squamous Cell Carcinoma

Study Design The study plans to enroll 38 patients. A Simon's two-stage design is employed. Based on historical data, the objective response rate (ORR) for patients meeting the inclusion criteria and receiving PD-1 inhibitor monotherapy is approximately 30%. The expected ORR for the combination of Pucotenlimab and Vebreltus is 55%. With a one-sided α=0.05 and 80% power, 9 patients will be enrolled in the first stage. If ≥2 patients achieve a partial response (PR) or complete response (CR), the study will proceed to the second stage. An additional 25 patients will be enrolled in the second stage, resulting in a total of 34 patients. If ≥15 patients in the total population achieve a PR, the study endpoint is considered met. Accounting for a 10% dropout rate, a total of 38 patients will be enrolled.

Study Procedures After providing full informed consent and passing screening, eligible subjects will receive treatment with Vebreltus 2.0 mg/kg and Pucotenlimab 200 mg. On the first day of each treatment cycle, patients will receive an intravenous infusion of Pucotenlimab (infusion duration: 60 min ± 15 min, with the first cycle infusion lasting no less than 60 minutes). At least 30 minutes after the completion of the Pucotenlimab infusion, the Vebreltus infusion will commence (infusion duration: 60 min ± 15 min, with the first cycle infusion lasting no less than 60 minutes). Patients will receive the combination therapy once every 3 weeks until completion of 2 years of treatment or until the occurrence of a protocol-defined treatment discontinuation event. Following the end of treatment, each subject will undergo a 30-day (+7 days) safety follow-up to monitor adverse events and clinically relevant events. Post-treatment survival follow-up will be conducted every 12 weeks (±7 days). For subjects who discontinue treatment for reasons other than disease progression/death and do not initiate new anti-cancer therapy, tumor imaging assessments will continue per the original schedule until disease progression, initiation of new anti-cancer therapy, withdrawal of consent, loss to follow-up, or death, whichever occurs first.

After enrollment, tumor response will be assessed according to RECIST v1.1 and iRECIST criteria. Imaging evaluations will be performed every 6 weeks (±7 days) from the first dose for the first 54 weeks, and then every 9 weeks (±7 days) thereafter (regardless of any delays in study drug administration), until iRECIST-confirmed progressive disease (iPD), initiation of new anti-cancer therapy, withdrawal of informed consent, loss to follow-up, or death, whichever occurs first.

Exploratory Analysis This study will analyze the correlation between biomarkers in patient tumor tissue/blood samples (e.g., EGFR expression, PD-L1 CPS score, TILs) collected before and after treatment and clinical efficacy endpoints (e.g., ORR, PFS, DoR).