This is a multicenter, single-arm, phase 2 clinical trial designed to evaluate the clinical efficacy of combination therapy with zanzalintinib and pembrolizumab in patients with locally advanced intermediate- to high-risk, high-risk, or resectable metastatic clear cell renal cell carcinoma.
The neoadjuvant treatment period consists of a total of 6 cycles; pembrolizumab is administered every 3 weeks, and zanzalintinib is administered orally once daily. A drug washout period of at least 21 days is required prior to the last dose before surgery.
Surgery will be performed after completion of the neoadjuvant treatment and following a drug washout period of at least 21 days.
The adjuvant treatment period begins at least 28 days after surgery, and pembrolizumab is administered every 3 weeks for a total of 11 cycles.
Radiologic response assessments are conducted at predefined time points during the neoadjuvant period, and pathologic response is evaluated using resected tissue obtained at the time of surgery.
* Study duration: Approximately 30 months (18 months for enrollment + 12 months for treatment and follow-up)
* Planned sample size: 48 patients (including an estimated 10% dropout rate) Tumor size and disease stage will be assessed using baseline imaging performed prior to treatment, and tumor response will be evaluated through predefined scheduled imaging assessments conducted during treatment. Tumor response will be evaluated during treatment via imaging at regular intervals per cycle. Surgery will be scheduled after the completion of 6 cycles, following a minimum 21-day washout period (±7 days at the investigator's discretion). If postoperative recovery is adequate (at least 28 days, ±14 days at the investigator's discretion), adjuvant Pembrolizumab treatment will commence.