Results of a phase 2 study indicate that toripalimab and lenvatinib in combination with GemOx chemotherapy provide antitumor activity and reasonable tolerability in patients with advanced intrahepatic CCA.
A phase 2 study evaluated the safety and efficacy of the anti–PD-1 agents toripalimab and lenvatinib in combination with oxaliplatin and gemcitabine (GemOx) chemotherapy in patients with locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA). Results of the study were presented at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
From May 2019 to October 2019, patients with pathologically confirmed advanced iCCA were enrolled at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible patients received intravenous (IV) toripalimab 240 mg once every 3 weeks, oral lenvatinib 8 mg once daily, gemcitabine 1 g/m2 on day 1 and day 8, and IV oxaliplatin 85 mg/m2 once every 3 weeks for 6 cycles, until disease progression, unacceptable toxicity, or voluntary withdrawal. The primary end point was objective response rate (ORR) per RECIST version 1.1. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). An exploratory biomarker analysis was performed. Date of data cutoff was February 1, 2021.
A total of 30 patients with iCCA were enrolled in the study. The mean participant age was 56.5 years. The majority of patients were male (63%) and had stage IIIB/IV disease. The majority of participants were PD-L1 negative (66.7%) and had a DNA damage repair (DDR)-related gene mutation (70%). At a median follow-up of 16.6 months, an ORR of 80% was achieved, including 1 complete response. The disease control rate was 93.3%, the median duration of response was 9.8 months, and the median PFS was 10.0 months. The median OS was not reached, and the 12-month OS rate was 73.3%.
Common any-grade treatment-related adverse events (AEs) occurring in ≥30% of participants included vomiting, abnormal electrocardiogram, increased aspartate aminotransferase level, neutropenia, fatigue, nausea, numbness, gingivitis, rash, thrombocytopenia, anorexia, insomnia, abnormal pain, and fever. Grade ≥3 AEs were reported in 50% of patients. Common AEs occurring in ≥10% of patients included neutropenia (10%), jaundice (10%), rash (6.7%), and proteinuria (6.7%). No grade 5 AEs were reported. Biomarker analysis found that a high ORR was significantly associated with positive PD-L1 expression (P = .048) and DDR-related mutations (P = .022).
These results indicate that toripalimab and lenvatinib in combination with GemOx chemotherapy is associated with considerable antitumor activity and reasonable tolerability in patients with advanced iCCA.
Source: Jian Z, Fan J, Shi G-M, et al. Gemox chemotherapy in combination with anti-PD1 antibody toripalimab and lenvatinib as first-line treatment for advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. J Clin Oncol. 2021;39(suppl_15):4094-4094.
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