P14.06 Toripalimab in Combination With Bevacizumab and Platinum-Based Chemotherapy in Patients with Untreated Advanced PSC: A Phase II Study

Abstract

Although immunotherapy has emerged as a standard treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutation, there are still insufficient data on the efficacy of immunotherapy for patients with pulmonary sarcomatoid carcinoma (PSC). Due to a high tumor mutation burden and great prevalence of programmed cell death ligand 1 (PD-L1) in PSC than other subtypes of NSCLC, immunotherapy may provide promising efficacy in advanced PSC patients. Multiple immune-monotherapy or combination with chemotherapy case studies and doublet immunotherapy based on a phase II study (NCT03022500) suggested the survival benefit of immunotherapy in advanced PSC. Blood-vessel invasion as an independent factor associated with PD-L1 expression and poor prognosis in PSC, early application of anti-angiogenesis may enhance patients' response to immunotherapy. The application of anti-programmed cell death protein 1 (PD-1) antibody combined with platinum-based chemotherapy plus anti-angiogenesis in untreated advanced PSC is worth exploring. Toripalimab, a humanized IgG4 monoclonal antibody against PD-1, achieved partial response (PR) for second-line advanced PSC in a recent case report (Jiao Y Oral Oncology 2020). Based on these pieces of evidence, we explore the combination of toripalimab with platinum-based chemotherapy and bevacizumab in patients with untreated advanced PSC. This is an open-label, multicenter, single-arm, phase II study that aims to evaluate the efficacy and safety of toripalimab combination with platinum-based chemotherapy and bevacizumab in patients with untreated advanced PSC. Key eligibility criteria include age 18-75 years with Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed PSC, at least 1 measurable lesion per RECIST v1.1 that not received radiotherapy, and no prior anti-PD-1 or anti-PD-L1 therapy for stage IV PSC. Patients will be excluded if they have evidence of mutations in either EGFR, ROS-1, ALK, or c-MET. 27 untreated advanced PSC patients at 5 sites will be enrolled in Chengdu city, Sichuan province of China. All patients will receive toripalimab (240 mg, d1) combined with bevacizumab (7.5 mg/kg, d1) and nab-paclitaxel (260 mg/m2, d1 or 130 mg/m2, d1,8) plus carboplatin (AUC= 4-5, d1) of a 21-day cycle for a maximum of 6 cycles. Patients will continue to receive maintenance therapy with toripalimab and bevacizumab until disease progression or died of two years. The primary endpoint is progression-free survival (PFS) by investigator assessment per RECIST v1.1. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), the patient-reported outcome (PRO), and safety data per NCI-CTC AE 4.0.3. Enrollment for this trial is open in April of this year and will continue for 12 months. Not applicable. Not applicable.