56P - Anti-PD1 antibody toripalimab, lenvatinib and gemox chemotherapy as first-line treatment of advanced and unresectable intrahepatic cholangiocarcinoma: A phase II clinical trial

Background

The outcome of advanced intrahepatic cholangiocarcinoma (ICC) remains poor with current gemcitabine-based chemotherapy. This study is to evaluate the survival benefit of anti-PD1 agent toripalimab, lenvatinib in combination with oxaliplatin and gemcitabine (Gemox) chemotherapy.

Methods

The study was an open-label, single-arm, phase II trial. Unresectable, locally advanced or metastatic ICC patients (pts) were given 240 mg toripalimab Q3W via intravenous (IV) infusion, 8mg lenvatinib QD orally, and 1g/m² gemcitabine on Day 1 and Day 8, and 85 mg/m² oxaliplatin Q3W by IV for 6 cycles. The primary outcome was the objective response rate (ORR). The response was evaluated according to RECIST v1.1. Secondary outcomes included safety, progression-free survival (PFS) and overall survival (OS). Whole exome sequencing was performed on tumor tissues and PD-L1 expression was determined by immunohistochemistry staining.

Results

From May 2019 to Oct 2019, 30 pathologically confirmed advanced ICC pts with a mean age of 56.5 (range, 25-73) years, including 11 women (37%), were enrolled at Zhongshan Hospital, Fudan University (one pt quitted voluntarily). The ORR was 80% (24/30; 95% CI: 61.4%-92.3%), and disease control rate (DCR) was 93.3% (28/30; 95% CI:77.9%-99.2%). One pt achieved a complete response (CR). Two pts with locally metastatic disease were down-staged and they subsequently underwent resection. Median follow-up was 8.4 months by May 1, 2020. 12 pts had disease progression and 4 pts (4/12) have died. The median PFS and OS have not been reached. The median duration of response has not been reached and responses were ongoing in 16/24 (66.7%) pts at data cutoff. 6-months OS rate was 90%. 43% (13/30) of pts experienced Grade 3 or higher adverse events (AEs). ORR was significantly associated with PD-L1 expression and DNA damage repair (DDR)-related mutations in tumor samples.

Conclusions

The combination of toripalimab, lenvatinib with Gemox chemotherapy was tolerable and showed promising ORR in patients with advanced ICC. These findings warrant further study in a large randomized trial.

Clinical trial identification

NCT03951597.

Editorial acknowledgement

Legal entity responsible for the study

Zhongshan Hospital, Fudan University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.