A Phase 2 Primary Analysis of Tislelizumab Plus Lenvatinib and GEMOX as Conversion Therapy in Potentially Resectable Locally Advanced BTC (ZSAB-TransGOLP)

Previously, a phase 2 study documented favorable outcomes when combining gemcitabine and oxaliplatin (GEMOX) with lenvatinib and a programmed cell death protein-1 antibody (GOLP regimen) as a first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA). These findings suggest that the GOLP regimen holds promise as a conversion therapy for patients with potentially resectable advanced biliary tract cancer (BTC).^1,2

At ASCO GI, Jia Fan, PhD, presented results from a phase 2 trial (NCT05156788) that investigated the efficacy and safety of GOLP as conversion therapy in potentially resectable and locally advanced BTC.

Patients received tislelizumab (200 mg, every 3 weeks), lenvatinib (8 mg, once a day), GEMOX chemotherapy (every 3 weeks), gemcitabine (1000 mg/m², administered on days 1 and 8), and oxaliplatin (85 mg/m², administered on day 1). Every 3 to 6 cycles, tumor responses were evaluated according to RECIST (version 1.1). A multidisciplinary team evaluated the resectability. For patients eligible for surgery, capecitabine alone was given as adjuvant therapy after radical surgery.

Patients not eligible for surgery continued with the original treatment regimen until disease progression or intolerable toxicity.

The primary endpoint was the R0 resection rate, and secondary endpoints included objective response rate (ORR), disease control rate (DCR), major partial response (MPR), relapse-free survival, progression-free survival, and overall survival.

In this study, the GOLP regimen was found to be highly effective and safe as a conversion therapy for potentially resectable locally advanced BTC.

In total, 41 patients were enrolled in the study from December 2021 to July 2023. Patients had a mean age of 57 years; 21 were male, and 20 were female. Additionally, 87.8% of patients had iCCA, 7.3% had perihilar bile duct cancer, and 4.9% had gallbladder cancer. The tumor, node, and metastasis stages were II, IIIA, IIIB, and IIIC for 2.4%, 34.1%, 58.5%, and 4.9% of patients, respectively.

At the September 10, 2023, cutoff, the mean follow-up was 7.7 months. Comparatively, 39 patients completed ≥3 cycles of conversion therapy, and 7 patients were still undergoing scheduled conversion therapy. The ORR was 43.9%, and the DCR was 87.8%.

The median duration of therapy before surgery was 2.9 months (95% confidence interval, 2.6-4.6), the R0 resection rate was 48.8%, and 2 patients underwent R1 resection. Additionally, 9.1% of patients had a pathologic complete response, and 22.7% had an MPR.

The most common grade 3/4 treatment-related adverse events (AEs) included neutropenia (34.1%), increased gamma-glutamyl transpeptidase (19.5%), and leukopenia (14.6%). No AEs in grade 5 were reported.

In this study, the GOLP regimen was found to be highly effective and safe as a conversion therapy for potentially resectable locally advanced BTC.

The survival data of these patients will continue to be followed.²

References

1. Shi GM, Huang XY, Wu D, et al. Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. Signal Transduct Target Ther. 2023;8(1):106.
2. Fan J, Zhou J, Shi G, et al. A single-arm, multi-center phase II study of tislelizumab combined with lenvatinib and GEMOX as conversion therapy in potentially resectable locally advanced biliary tract cancer (ZSAB-TransGOLP): a primary analysis. San Francisco, CA, & online: presented at ASCO Gastrointestinal Cancers Symposium; January 18-20, 2024: poster C13.