Camrelizumab plus apatinib for advanced renal cell carcinoma patients after first-line tyrosine kinase inhibitor treatment failure: A multicenter phase II trial.

person Lijuan Jiang Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Lijuan Jiang, Xia Zheng, Wensu Wei, Yulu Peng, Deling Wang, Zhiling Zhang, Shengjie Guo, Hui Han, Xiuyu Cai, Fangjian Zhou, Pei Dong

Authors person Lijuan Jiang Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Lijuan Jiang, Xia Zheng, Wensu Wei, Yulu Peng, Deling Wang, Zhiling Zhang, Shengjie Guo, Hui Han, Xiuyu Cai, Fangjian Zhou, Pei Dong Organizations Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Medical Imaging, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Urology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China, Department of Urology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of General Internal Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China Abstract Disclosures Research Funding No funding sources reported Background: Previous studies have demonstrated the benefit of combining immunotherapy with antiangiogenic agents in patients with advanced renal cell carcinoma (aRCC). The efficacy of apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (TKI), has been documented in aRCC. In contrast, the efficacy of camrelizumab, a PD-1 inhibitor, has not been reported in RCC, although its efficacy and safety have been established in various cancer types. This study aims to evaluate the efficacy and safety of camrelizumab plus apatinib in aRCC following the failure of first-line TKI therapy. Methods: This multicenter, single-arm, phase II trial enrolled patients with aRCC who had failed first-line TKI treatment. Patients received 200 mg of camrelizumab intravenously every two weeks and 250 mg of apatinib orally once daily until disease progression or unacceptable toxicity occurred, with camrelizumab treatment lasting up to two years. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Between August 2020 and January 2024, 35 patients were enrolled in the study and received treatment. The median age was 57 years (range: 39-81), with 31 (88.6%) being male. A total of 27 (77.1%) patients presented with lung metastases. As of the cut-off date, January 8, 2024, the median follow-up duration was 16.5 months (range: 0-33). Of these patients, 12 (34.3%) achieved a partial response, and 17 (48.6%) maintained stable disease, resulting in an objective response rate of 34.3% (95% confidence interval [CI], 19.1-52.2) and a disease control rate of 82.9% (95% CI, 66.4-93.4). Two out of five patients with progressive disease (PD) benefited from continued treatment with camrelizumab plus apatinib for more than 4 months after the first PD. The median PFS was 10.0 months (95% CI, 6.1-14.9), and the median overall survival was 28.4 months (95% CI, 19.7-not reached). Of all patients, 27 (77.1%) experienced treatment-related adverse events of grade 3 or higher, with the most common being proteinuria (25.7%), hypertension (20.0%), and alanine aminotransferase increased (14.3%) and aspartate aminotransferase increased (14.3%). Conclusions: The combination of camrelizumab and apatinib demonstrates encouraging antitumor activity and a favorable safety profile as a second-line treatment option for patients with aRCC. Clinical trial information: ChiCTR2000034384 . Efficacy endpoints. Endpoints All (n=35) Best overall response, n (%) Partial response 12 (34.3) Stable disease 17 (48.6) Progressive disease 5 (14.3) Not available 1 (2.9) Objective response rate, %, 95%CI 34.3 (19.1, 52.2) Disease control rate, %, 95%CI 82.9 (66.4, 93.4) Progression-free survival, months, median, 95%CI 10.0 (6.1-14.9) Overall survival, months, median, 95%CI 28.4 (19.7-NR)

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