Camrelizumab plus famitinib for advanced renal cell carcinoma or unresectable urothelial carcinoma: Updated results from a phase II trial.

person Yuan-Yuan Qu Department of Urology Surgery, Fudan University Shanghai Cancer Center, Shanghai, China info_outline Yuan-Yuan Qu, Qing Zou, Hongqian Guo, Nianzeng Xing, Zhongquan Sun, Weiqing Han, Hong Luo, Shujie Xia, Xuepei Zhang, Chaohong He, Hailiang Zhang, Jinling Cai, Xiao Zhang, Quanren Wang, Dingwei Ye

Authors person Yuan-Yuan Qu Department of Urology Surgery, Fudan University Shanghai Cancer Center, Shanghai, China info_outline Yuan-Yuan Qu, Qing Zou, Hongqian Guo, Nianzeng Xing, Zhongquan Sun, Weiqing Han, Hong Luo, Shujie Xia, Xuepei Zhang, Chaohong He, Hailiang Zhang, Jinling Cai, Xiao Zhang, Quanren Wang, Dingwei Ye Organizations Department of Urology Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Urology Surgery, Jiangsu Cancer Hospital, Nanjing, China, Urinary Surgery Center, Nanjing Drum Tower Hospital, Nanjing, China, Urinary Surgery Center, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China, Department of Urology Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China, Urinary Surgery Center, Hunan Cancer Hospital, Changsha, China, Department of Urology Surgery, Chongqing Cancer hospital, Chongqing, China, Urology Center, Shanghai General Hospital, Shanghai, China, Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, Department of Urology Surgery, Henan Cancer Hospital, Zhengzhou, China, Clinical Research & Development, Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China, Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China, Fudan University Shanghai Cancer Center, Shanghai, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Jiangsu Hengrui Medicine Co., Ltd Background: Considering the synergistic/additive effect of PD-1 blockade and angiogenesis inhibition, we conducted an open-label, multi-center phase II study of camrelizumab (an anti-PD-1 antibody) plus famitinib (a TKI against VEGFR-2, PDGFR, c-kit, and FGFR) in pts with heavily treated advanced renal cell carcinoma (RCC) and unresectable urothelial carcinoma (UC). Methods: Based on an adaptive two-stage design, 22 pts were enrolled in the RCC and UC cohort, respectively, at stage 1; if there were ≥7 responders of the 22 pts, enrollment would be extend to 33 at stage 2. Pts received famitinib 20 mg orally QD plus camrelizumab 200 mg IV Q3W. Primary endpoint was ORR per RECIST v1.1. Preliminary data at stage 1 were reported at ASCO 2020 annual meeting (#5085). More than 7 pts in each cohort had CR/PR during stage 1; enrollment of stage 2 had been completed, and the data are firstly reported here. Results: 74 pts (38 advanced RCC and 36 unresectable UC) were enrolled from Jan 23, 2019 to Dec 14, 2020. In RCC cohort, 65.8% of pts had received ≥1 prior VEGFR inhibitors. In UC cohort, all pts had progressed on or relapsed after a platinum-containing chemotherapy. As of Jan 10, 2021, median time from enrollment to data cutoff was 18.8 mos (range, 8.5-22.7) for RCC cohort and 7.0 mos (range, 0.9-23.6) for UC cohort. In RCC cohort, ORR was 63.2% (95% CI, 46.0-78.2; 24 PRs), DCR was 89.5% (95% CI, 75.9-95.8), median DOR was not reached (range 2-19+ mos), mPFS was not reached, and 12-mo OS rate was 88.0%. Most pts (92.1%) had reduction in target lesions, and median reduction was 47% from baseline. ORR was 84.6% (95% CI, 57.8-97.3; 11/13) for untreated RCC pts and 52.0% (95% CI, 31.3-72.2; 13/25) for pre-treated pts; DCR was 100% (95% CI, 77.2-100.0) and 84.0% (95% CI, 65.3-93.6), mPFS was not reached and 13.4 mos (95% CI: 4.1-21.0), respectively. In UC cohort, of the 33 pts with post-baseline efficacy evaluation, ORR was 33.3% (95% CI, 19.8-50.4; 1 CR, 10 PRs), DCR was 60.6% (95% CI, 43.7-75.3), median DOR was not reached (range 1.0+-16.7+ mos), mPFS was 6.4 mos (95% CI, 2.1-11.8), and mOS was not reached. ORR trended to be higher for bladder cancer (43.8%, 7/16) than upper tract urothelial carcinoma (25.0%, 4/16). Treatment-related AEs (TRAEs) occurred in 97.3% of 74 pts. Grade 3 or 4 TRAEs occurred in 63.5% of pts, mainly hypertension (23.4%), decreased platelet count (21.3%), proteinuria (17.0%), anemia (14.9%), and palmar-plantar erythrodysesthesia syndrome (14.9%). 1 pt died of TRAE (multiple organ dysfunction syndrome). Conclusions: Camrelizumab plus famitinib showed potent anti-tumor activity in pts with advanced RCC and UC with no new safety concerns. Additionally, promising ORR and durable DOR were observed in pts with heavily-treated RCC. These results support further investigation in these settings. Clinical trial information: NCT03827837