Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial

Abstract

Background: Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.

Methods: In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.

Results: 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).

Conclusion: Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.

Trial registration number: NCT03486678.

Keywords: biomarkers; clinical trials; immunotherapy; phase II as topic; tumor.

Conflict of interest statement

Competing interests: YWS is an employee of Nanjing Geneseeq Technology Inc. HL is an employee of Jiangsu Hengrui Medicine Co., Ltd. JZ is employees of Shanghai 3D Medicines Inc. GW is employees of Burning Rock Biotech.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Flow of participants in the study.

Figure 2

Kaplan-Meier curves for progression-free survival and overall survival in the intent-to-treat (ITT) population (A, B) and primary site subgroups (C, D).

Figure 3

Characteristics of objective response in patients with camrelizumab plus gemcitabine and oxaliplatin (GEMOX). (A) Duration of response (N=20). (B) The maximum percentage reduction from baseline in target lesions (N=36). One patient discontinued because of treatment-related adverse effect before first radiographic assessment and was not included.

Figure 4

Distribution of genetic variations associated with treatment response. ORR, objective response rate; PD, progressive disease; PD-L1, programmed cell death ligand-1; PR, partial response; SD, stable disease.