A phase II clinical study of camrelizumab plus apatinib in combination with stereotactic body radiotherapy (SBRT) for advanced non-clear cell renal cell carcinoma (nccRCC).

557 Background: The efficacy of targeted therapy alone in the treatment of advanced nccRCC remains unsatisfactory, but its combination with immunotherapy and/or SBRT is worth exploring. In this study, we aimed to investigate the safety and efficacy of camrelizumab plus apatinib combined with SBRT for advanced nccRCC. Methods: This is a single-arm, phase Ⅱ study enrolling recurrent/metastatic nccRCC patients (pts), for whom the cytoreductive SBRT (defined as the lesions receiving SBRT≥50% of the tumor burden) can be safety applied (ChiCTR2000034727). No liver or brain metastasis was allowed. Eligible pts received camrelizumab (200mg, day 1) (for wgt <= 40kg, 3mg/kg) and apatinib (250mg, once daily, day 1-14) in a 2-week cycle. Cytoreductive SBRT (20-45 Gy, 1-5 fractions) was performed between the 1 st and the 3 rd administration of camrelizumab. The primary endpoint of this study was the objective response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), safety, and quality of life. Results: From Oct. 26, 2020, and Sep. 6, 2024, a total of 37 pts were enrolled, and 32 pts were evaluable for efficacy after SBRT. Among them, 11 (34.4%) had Xp11.2 translocation, 10 (31.3%) pts had papillary, 5 (15.6%) had fumarate hydratase-deficient, 2 (6.3%) had chromophobe, 1 (3.1%) had collecting duct, 1 (3.1%) had sarcomatoid, and 2 (6.3%) had unclassified histology. 3 (9.4%) pts were local-reginal recurrent, whereas 14 (43.8%) were oligometastatic, and 15 (46.9%) were multiple metastatic. 31 (96.9%) pts were IMDC intermediate or high risk, and 10 (31.3%) pts received at least one prior systemic therapy. With a median follow-up time of 18.9 months, 23 (71.9%) pts achieved ORR, of which 12 (37.5%) pts had complete response and 11 (34.4%) pts had partial response. The DCR was 93.8%, and the median PFS was 19.0 months. The most common adverse events (AEs) of any grade were creatinine increased (n = 21, 65.6%), followed by anemia (n = 19, 59.4%), aspartate aminotransferase (AST) increased (n = 19, 59.4%), proteinuria (n = 19, 59.4%), and hypertension (n = 13; 40.6%). Grade 3 AEs occurred in 11 pts (4 proteinuria, 4 AST increased, 2 blood bilirubin increased, 2 rash, and 2 neutrophil counts decreased). The most common AEs after SBRT were nausea (n = 10; 31.3%). No grade 4-5 AEs occurred. Furthermore, the proportion of CD4+ and CD8+ lymphocytes in peripheral blood increased after SBRT and dropped to baseline levels after the 4 th and the 8 th cycle of camrelizumab, respectively. To the opposite, the proportion of CD19+ lymphocytes decreased after SBRT but continued to increase after the 2 nd circle of camrelizumab. Conclusions: Camrelizumab plus apatinib combined with SBRT showed promising antitumor activity and manageable toxicity in pts with recurrent/metastatic nccRCC. Clinical trial information: ChiCTR2000034727 .