Phase II clinical study of the safety and efficacy of sintilimab in combination with axitinib and stereotactic radiotherapy in the treatment of local-regional recurrent renal cell cancer.

e16511 Background: Currently, targeted agents and immunotherapy are applied to local-regional recurrent renal cell carcinoma (LRRCC). The combination with systemic therapy and stereotactic radiotherapy (SBRT) is worth exploring. In the present study, we aimed to investigate the efficacy and safety profile of sintilimab plus axitinib combined with SBRT in the treatment for LRRCC. Methods: This was a single-arm, phase II study enrolled LRRCC patients (pts), for whom the SBRT can be safety applied for all the recurrent lesions visible on imaging. Eligible pts received sintilimab (200mg, day 1) and axitinib (5mg, bid, day 1-21) in a 21d cycle. SBRT (35-45Gy/5 fractions) was performed before the third administration of sintilimab. The primary endpoint was progression-free survival (PFS). Results: From Oct 2021 to Jan 2024, 19 pts with a median age of 58 (range: 33-74) were enrolled. Among them, 9 (47.37%) pts had clear cell carcinoma. Nine (47.37%) pts were IMDC intermediate (7 pts) or high risk, and 8 (42.11%) pts recurred in less than 1 year after surgery. Seven(36.84%) pts received at least one prior systemic therapy. Four (21.05%) pts had recurrence in the renal fossa, while 3(15.79%) pts in retroperitoneal lymph node, 2(10.53%) pts in retroperitoneal lymph node with renal fossa and 10(52.63%) pts in intra-abdominal soft tissue. With a median follow-up of 9.5 months (range: 3.0-27.1m), 18 pts were evaluable for response. The median tumor volume was 37.47cc (range: 2.44-493.19cc). The overall response rate was 55.56% with 4 complete responses and 6 partial responses per RECIST v1.1. The median time-to-response was 5 months. The local control rate and the disease control rate were 100% and 94.44%, respectively. The median PFS was not reached, and the 9-month PFS rate was 94.44%. All 19 pts were evaluable for toxicity. Any-grade treatment-related adverse events (TRAEs) occurred in 16(84.21%) pts. The most common TRAEs were albuminuria (8/19; 42.11%), nausea (8/19; 42.11%), hypertension (7/19; 36.84%), and diarrhea (7/19; 36.84%). Grade 3 or higher TRAEs occurred in 6/19(31.58%). Conclusions: Sintilimab plus axitinib combined with SBRT showed promising antitumor activity and manageable toxicity in pts with LRRCC. Clinical trial information: ChiCTR2100049523 .