Rucaparib and Nivolumab as Maintenance Therapy Following Chemotherapy in Patients With Advanced BTC: BilT-02

September 2023, Vol 4, No 3

Despite chemotherapy, patients with advanced biliary tract cancer (BTC) have a median overall survival (OS) of <12 months.1 Positive results from the TOPAZ-1 trial, which investigated durvalumab and gemcitabine/cisplatin (GemCis) vs GemCis alone in patients with advanced BTC, led to the addition of durvalumab to the current standard of care (GemCis) in these patients.2,3 To further improve outcomes in patients with advanced BTC, researchers are investigating novel combination therapies using immunotherapies and poly-ADP ribose polymerase (PARP) inhibitors. Nivolumab, a PD-1 inhibitor, blocks the interaction of PD-1 on T cells with PD ligands, PD-L1 and PD-L2, on tumor cells, restoring a patient’s tumor-specific T-cell response.3,4 In addition, studies indicate that cells with IDH1 mutations exhibit a diminished ability to mend double-stranded DNA breaks, rendering them potentially highly susceptible to PARP inhibition.5 At the 2023 ASCO meeting, Vaibhav Sahai, MBBS, MS, presented the results from the BilT-02 study.3

Vaibhav Sahai, MBBS, MS

BilT-02 was a phase 2, multicenter trial of the PARP inhibitor rucaparib and the PD-1 inhibitor nivolumab as maintenance therapy following progression after first-line platinum-based chemotherapy in patients with advanced BTC. The study sought to determine whether the addition of rucaparib and nivolumab as maintenance therapy following chemotherapy in patients with advanced BTC can improve outcomes. The primary study objective was to determine the progression-free survival (PFS) rate at 4 months when rucaparib and nivolumab were used as maintenance treatment.3 The secondary objective was to evaluate the clinical efficacy of this maintenance regimen by means of median PFS1 and OS1 (from start of study treatment), PFS2 and OS2 (from start of first-line platinum chemotherapy), and best objective response rate.3 A total of 31 patients with advanced BTC who were not eligible for curative resection and had received first-line platinum-based chemotherapy for 4 to 6 months without progression were enrolled in BilT-02.3 Of these, 19 had intrahepatic cholangiocarcinoma (CCA), 4 had extrahepatic distal CCA, and 7 had extrahepatic hilar CCA.3 Patients received 240 mg of nivolumab intravenously on days 1 and 15 and 600 mg of rucaparib orally twice a day on days 1 to 28 until disease progression or intolerance.3 The primary end point was not met, and the observed PFS rate at 4 months was 54.8%.3 The estimated median for PFS1 was 4.6 months, OS1 was 15.9 months, PFS2 was 9.9 months, and OS2 was 21.4 months.3

The most common grade 3 or greater treatment-related adverse events included fatigue (29%), anemia (22.6%), neutropenia (19.3%), and elevated aspartate aminotransferase (16.1%) and alanine transaminase (12.9%).3 Although the primary end point was not met, the combination was well tolerated, and initial efficacy observations warrant further evaluation of rucaparib and nivolumab as maintenance therapy in patients with advanced BTC.3


  1. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-1281.
  2. Oh D-Y, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1). NEJM Evid. 2022;1(8).
  3. Sahai V, Griffith KA, Mohan A, et al. Phase 2 multicenter trial of rucaparib and nivolumab as maintenance therapy following first-line platinum-based chemotherapy in patients with advanced biliary tract cancer. Poster presented at: ASCO 2023 Annual Meeting, June 2-6; Chicago, IL.
  4. Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer. 2017;8(3):410-416.
  5. Sulkowski PL, Corso CD, Robinson ND, et al. 2-hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci Transl Med. 2017;9(375).

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