Camrelizumab plus famitinib as first-line treatment for locally advanced or metastatic pulmonary sarcomatoid carcinomas (CAPSTONE): a multi-center, single-arm, phase 2 trial

Background The combination of immune checkpoint inhibitors and antiangiogenic agents has demonstrated a synergistic antitumor effect in numerous solid tumors, but has rarely been investigated in pulmonary sarcomatoid carcinoma (PSC). We assessed the activity and safety of camrelizumab (a programmed cell death-1 inhibitor) plus famitinib (an antiangiogenic agent) in patients with PSC. Methods CAPSTONE is an open-label, single-arm, Simon two-stage, phase 2 trial done at eight sites in China. Eligible patients were aged between 18 and 75 years and had previously untreated stage IIIB–IV pulmonary sarcomatoid carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients received intravenous camrelizumab 200 mg every 3 weeks and oral famitinib 20 mg once daily until disease progression or intolerable toxicity. The primary endpoint was confirmed objective response rate (ORR) as per RECIST version 1.1 in the full analysis set, which included all patients who received at least one dose of study drug. Safety was assessed in all as-treated patients. This study is registered at ClinicalTrials.gov, NCT04888429, and enrollment is complete. Findings Between August 4, 2021 and March 21, 2024, 28 patients were enrolled. With a median follow-up of 18.1 months, the confirmed ORR was 42.9% (95% confidence interval [CI] 24.5–62.8). The disease control rate was 85.7% (95% CI 67.3–96.0). The median duration of response was 16.0 months (95% CI 5.0–29.9); the median progression-free survival was 7.1 months (95% CI 3.5–12.5); and the median overall survival was 18.1 months (95% CI 10.3–28.1). Treatment-related adverse events (TRAEs) of grade 3 or more were observed in 10 (35.7%) patients, the most common being decreased platelet count (four [14.3%]) and decreased neutrophil count (three [10.7%]). Three (10.7%) patients discontinued camrelizumab, and three (10.7%) discontinued famitinib due to TRAEs. Two patients died of unknown cause, which were assessed by the investigator as possibly related to study treatment. Interpretation Camrelizumab plus famitinib showed antitumor activity in patients with locally advanced or metastatic PSC. This combination may be a potential first-line option for this patient population, and warrants further investigation in a large-sample trial. Funding National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2024ZD0519700), National Natural Science Foundation of China (62131009, 82472969), Innovation Research Group Program of the Natural Science Foundation of Hubei Province (2026AFA036), Hubei Provincial Health Science and Technology Innovation and Achievement Transformation Project, Jiangsu Hengrui Pharmaceuticals Co., Ltd.