Combination Immunotherapy with Ipilimumab and Nivolumab Shows Activity in Patients with Advanced Biliary Tract Cancer

The combination of a CTLA-4 inhibitor and a PD-1 inhibitor with ipilimumab (Yervoy) and nivolumab (Opdivo) has demonstrated superior efficacy compared with single-agent anti–PD-1 therapy in a previous study of patients with advanced melanoma and renal-cell carcinoma.¹

A study presented at the ASCO 2020 virtual annual meeting included patient populations with rare tumors, including a subset of patients with biliary tract cancer. The study investigators, led by Oliver Klein, MD, FRACP, Olivia Newton-John Cancer Research Institute, Heidelberg, Australia, analyzed the benefit of this dual blockade with ipilimumab and nivolumab in the cohort of patients with metastatic biliary tract cancer.²

The study included 39 patients with metastatic biliary tract cancer. The patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks. Treatment continued for up to 96 weeks or until disease progression or unacceptable toxicity. The response to therapy was assessed every 12 weeks, using Response Evaluation Criteria in Solid Tumors version 1.1.

The primary end point was disease control rate—complete response plus partial response plus stable disease. The exploratory end points included the correlation of efficacy with biomarkers, including PD-L1 expression and tumor mutation burden. A total of 33 (85%) patients had previously received at least 1 (range, 0-2) line of systemic treatment.

The overall response rate was 24%, the disease control rate was 44%, and the median duration of response was not reached (range, 2 months-≥26 months).

Responses were observed in 5 of the 16 patients with intrahepatic cholangiocarcinoma (CCA), in none of the 10 with extrahepatic CCA, and in 4 of the 13 patients with gallbladder cancer. None of the responding patients had tumors with microsatellite instability.

In addition, 2 patients with durable partial responses were subsequently rendered surgically free of disease.

The median overall survival was 5.7 and the progression-free survival was 2.9 months. A total of 22 (56%) patients had an immune-related adverse event, including 6 (17%) patients with grade 3 or 4 events.

The investigators concluded that the combination of ipilimumab and nivolumab demonstrated significant clinical activity in patients with microsatellite-stable biliary tract cancer.

References

1. Chae YK, Arya A, Iams W, et al. Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018;6:39.
2. Klein O, Kee D, Nagrial A, et al. Combination immunotherapy with ipilimumab and nivolumab in patients with advanced biliary tract cancers. J Clin Oncol. 2020;38(15_suppl):Abstract 4588.