Phase II trial of camrelizumab plus apatinib in combination with stereotactic body radiotherapy (SBRT) in patients with recurrent/metastatic non–clear-cell renal cell carcinoma (nccRCC).
Authors: Liu Ruiqi , Liu Yang , Wei Wensu , Zhang Zhiling , Gao Jianming , Guo Shengjie , Han Hui , Zhou Fangjian , Dong Pei , He Liru 
Published: June 2023

e16531 Background: Currently, the efficacy of targeted therapy alone in the treatment of recurrent/metastatic nccRCC remains unsatisfactory, but its combination with immunotherapy and/or SBRT is worth exploring. In the present study, we aimed to investigate the efficacy and safety profile of camrelizumab plus apatinib combined with SBRT in the treatment for recurrent/metastatic nccRCC. Methods: This was a single-arm, phase Ⅱ study enrolled 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). Pts were aged 18 years or older, ECOG performance status of 0 or 1, with at least one measurable tumor site, and without liver or brain metastasis. 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 first and the third administration of camrelizumab. The primary endpoint of this study was the objective response rate (ORR); secondary endpoints were 6-month progression-free survival (PFS) rate, PFS, overall survival, disease control rate, duration of response, safety, and quality of life. Results: Between Oct. 26, 2020, and Oct. 25, 2022, a total of 22 pts were screened and 19 pts were enrolled. Among them, 7 (36.8%) pts had papillary, 5 (26.3%) had Xp11.2 translocation, 2 (10.5%) had fumarate hydratase-deficient, 1 (5.3%) had chromophobe, 1 (5.3%) had collecting duct, 1 (5.3%) had sarcomatoid, and 2 (10.5%) had unclassified histology. 3 (15.8%) pts were local-reginal recurrent, whereas 12 (63.1%) were oligometastatic, and 4 (21.1%) were multiple metastatic. 18 (94.7%) pts were IMDC intermediate or high risk, and 7 (36.8%) pts received at least one prior systemic therapy. At the data cut-off date (Dec. 30, 2022), with a median follow-up time of 10.8 months, 13 (68.4%) pts achieved ORR, of which 7 (36.8%) pts had complete response and 6 (31.6%) pts had partial response. The DCR was 89.5%, and the 6-month PFS rate was 76.2%. The most common adverse events of any grade were creatinine increased (n=15, 78.9%), followed by anemia (n=14, 63.7%), and aspartate aminotransferase increased (n=14, 63.7%). Treatment-related AEs (TRAEs) occurred in 15 (78.9%) pts, including proteinuria (n=11, 57.9%), palmar-plantar erythrodysesthesia (n=9, 47.3%), hypothyroidism (n=7, 36.8%) and hypertension (n=5; 26.3%). Grade 3-4 TRAEs occurred in 3 pts (1 proteinuria, 1 hypertension, 1 rash). The most commonly diagnosed AE after SBRT was nausea (n=5; 26.3%). There were no deaths reported during this study. Conclusions: Camrelizumab plus apatinib combined with SBRT showed promising antitumor activity and manageable toxicity in pts with recurrent/metastatic nccRCC. Clinical trial information: ChiCTR2000034727 .