Combination Immunotherapy in Advanced Biliary Tract Cancers

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In a subgroup analysis of an Australian phase II trial reported in JAMA Oncology, Klein et al found that the combination of nivolumab and ipilimumab was active in patients with advanced biliary tract cancers.

Study Details

The phase II trial is enrolling patients with advanced rare cancers. The current subgroup analysis included 39 patients with advanced biliary tract cancers enrolled between December 2017 and December 2019 who were treated with nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab at 3 mg/kg every 2 weeks continued for up to 96 weeks or until disease progression or unacceptable toxicity. A total of 33 patients had disease progression after one or more lines of therapy and had tumor tissue available for biomarker research. The primary endpoint was disease control rate.



  • Nivolumab/ipilimumab produced a response rate of 23% and disease control rate of 43%.
  • Median duration of response was not reached.

Among all patients, objective responses (all partial responses) were observed in nine (23%) and stable disease was observed in eight (21%), yielding a disease control rate of 43%. All patients with objective response had received prior chemotherapy and none had a microsatellite-unstable tumor. Responses were observed in 4 (31%) of 13 patients with gallbladder carcinoma (disease control rate = 70%), 5 (31%) of 16 with intrahepatic cholangiocarcinoma (disease control rate = 44%), and 0 of 10 patients with extrahepatic cholangiocarcinoma. The median duration of response was not reached (range = 2.5–≥ 23 months). Median progression-free survival was 2.9 months (95% confidence interval [CI] = 2.2–4.6 months) and median overall survival was 5.7 months (95% CI = 2.7–11.9 months).


Immune-related adverse events of any grade occurred in 49% of patients, with the most common being rash or pruritus (33%, all grade 1 or 2). Grade 3 or 4 immune-related adverse events occurred in 15% of patients and consisted of thyroiditis/hypothyroidism in one patient, hypophysitis in two, hepatitis in one, enterocolitis/diarrhea in one, and gastritis in one. No treatment-related deaths were reported.

The investigators concluded, “This subgroup analysis of a phase II clinical trial found that combination immunotherapy with nivolumab and ipilimumab was associated with substantial positive outcomes [in] patients with advanced biliary tract cancers. This treatment compares favorably to single-agent anti–PD-1 therapy and warrants further investigation. Ongoing translational research is focused on identifying biomarkers that can predict treatment response.”

Oliver Klein, FRACP, MD, of Olivia Newton-John Cancer Centre, Austin Hospital, Heidelberg, Victoria, Australia, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit