Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Sep 1;6(9):1405-1409.
doi: 10.1001/jamaoncol.2020.2814.

Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial

Oliver Klein  1   2 , Damien Kee  1   3 , Adnan Nagrial  4 , Ben Markman  5   6 , Craig Underhill  7 , Michael Michael  3 , Louise Jackett  8 , Caroline Lum  5 , Andreas Behren  2   9 , Jodie Palmer  2   9 , Niall C Tebbutt  1   10 , Matteo S Carlino  4 , Jonathan Cebon  1   2   9
Affiliations
Clinical Trial

Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial

Oliver Klein et al. JAMA Oncol. .

Abstract

Importance: Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients with advanced disease have a poor outcome with current therapies.

Objective: To evaluate the efficacy and safety of combination immunotherapy with nivolumab and ipilimumab in patients with advanced biliary tract cancers.

Design, setting, and participants: The CA209-538 prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced rare cancers including patients with biliary tract cancers. This subgroup analysis evaluated 39 patients from CA209-538 with biliary tract cancers who were enrolled from December 2017 to December 2019. Most of the patients (n = 33) had experienced disease progression after 1 or more lines of therapy and had tumor tissue available for biomarker research.

Interventions: Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks and continued for up to 96 weeks until disease progression or the development of unacceptable toxic events.

Main outcomes and measures: The primary end point was disease control rate (complete remission, partial remission, or stable disease) as assessed by RECIST 1.1.

Results: Among the 39 patients included in this subgroup analysis of a phase 2 clinical trial (20 men, 19 women; mean [range] age, 65 [37-81] years), the objective response rate was 23% (n = 9) with a disease control rate of 44% (n = 17); all responders had received prior chemotherapy, and none had a microsatellite unstable tumor. Responses were exclusively observed in patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma. The median duration of response was not reached (range, 2.5 to ≥23 months). The median progression-free survival was 2.9 months (95% CI, 2.2-4.6 months), and overall survival was 5.7 months (95% CI, 2.7-11.9 months). Immune-related toxic events were reported in 49% of patients (n = 19), with 15% (n = 6) experiencing grade 3 or 4 events.

Conclusions and relevance: This subgroup analysis of a phase 2 clinical trial found that combination immunotherapy with nivolumab and ipilimumab was associated with substantial positive outcomes patients with advanced biliary tract cancers. This treatment compares favorably to single-agent anti-programmed cell death protein 1 (anti-PD-1) therapy and warrants further investigation. Ongoing translational research is focused on identifying biomarkers that can predict treatment response.

Trial registration: ClinicalTrials.gov Identifier: NCT02923934.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Klein reports speaker fees from Bristol-Myers Squibb and MSD, travel support and personal fees from Bristol-Myers Squibb, personal fees from MSD Australia outside the submitted work, and grants from the Federal Department of Health Australia during the conduct of the study; Dr Kee reports honoraria/advisory board fees and personal fees from Novartis and travel and other support from Bristol-Myers Squibb outside the submitted work; Dr Nagrial reports personal fees from Bristol-Myers Squibb, MSD, Roche, and AstraZeneca outside the submitted work. Dr Markman reports honoraria/advisory board fees from Novartis and Amgen and nonfinancial support from Akesobio outside the submitted work; Dr Underhill reports grants from Border Medical Oncology Research Unit during the conduct of the study; Dr Palmer reports support from the Olivia Newton-John Cancer Research Institute during the conduct of the study; Dr Tebbutt reports personal fees from Bristol-Myers Squibb outside the submitted work; Dr Carlino reports personal fees from Bristol-Myers Squibb, MSD, personal Novartis, Amgen, Pierre Fabre, Merck Serono, Sanofi, Ideaya, Nektar, and Eisai and honoraria/advisory board fees from Bristol-Myers Squibb, Amgen, Novartis, MSD, Roche, Pierre Fabre, Ideaya, Sanofi, Merck, and Nektar outside the submitted work. Dr Cebon reported grants from Bristol-Myers Squibb during the conduct of the study and honoraria/advisory board fees from Bristol-Myers Squibb, Amgen, Novartis, and MSD outside the submitted work. No other disclosures are reported.

Figures

Figure.
Figure.. Kaplan-Meier Curve of Overall Survival and Progression Free Survival for the Entire Cohort (A, B) and Previously Treated Patients (C, D)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New Horizons for Precision Medicine in Biliary Tract Cancers. Cancer Discov. 2017;7(9):943-962. doi:10.1158/2159-8290.CD-17-0245 - DOI - PMC - PubMed
    1. Nakamura H, Arai Y, Totoki Y, et al. . Genomic spectra of biliary tract cancer. Nat Genet. 2015;47(9):1003-1010. doi:10.1038/ng.3375 - DOI - PubMed
    1. Jusakul A, Cutcutache I, Yong CH, et al. . Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. Cancer Discov. 2017;7(10):1116-1135. doi:10.1158/2159-8290.CD-17-0368 - DOI - PMC - PubMed
    1. Valle J, Wasan H, Palmer DH, et al. ; ABC-02 Trial Investigators . Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-1281. doi:10.1056/NEJMoa0908721 - DOI - PubMed
    1. Lamarca A, Palmer DH, Wasan HS, et al. . ABC-06 vertical bar A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC plus mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J Clin Oncol. 2019;37(15).doi:10.1200/JCO.2019.37.15_suppl.4003 - DOI

Publication types

MeSH terms

Associated data