ADJUBIL: A phase II study of immunotherapy with durvalumab and tremelimumab in combination with capecitabine or without capecitabine in adjuvant situation for biliary tract cancer—The IKF/AIO-ADJUBIL trial.
Year: 2025
Type: conference-abstract
Abstract: 4132 Background: Patients (pts) with biliary tract cancer (BTC) still have a poor outcome with limited effective treatment options (only 20% of pts eligible for surgically curative resection, 5-year OS rates < 10%). SOC for BTC is treatment with capecitabine according to the UK BILCAP trial, even though it was formally negative. Based on positive data (TOPAZ-1 and MediTreme trial in BTC, HIMALAYA trial for the STRIDE regimen in HCC), IO combination in the adjuvant setting seems promising. In preclinical studies – particularly in cholangiocarcinoma (CC) –antibody combinations showed stronger and more durable anti-tumor effects than monotherapy, due to synergistic impact on the tumor’s immunosuppressive microenvironment. The ADJUBIL trial aimed at evaluating the clinical activity of the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab with or w/o capecitabine in pts with resectable BTC in the adjuvant setting in a pick-the-winner design. The winner of ADJUBIL could be tested in a follow-up phase 2/3 trial against the current SOC capecitabine. Methods: In the open-label, multicenter phase II ADJUBIL trial treatment-naïve pts with BTC after curative surgery (R0/R1) were randomized (1:1) to receive either tremelimumab (300 mg, once on D1, cycle 1) plus durvalumab (1500 mg, Q4W; max. 12 months), with (arm A) or w/o (arm B) capecitabine (1250 mg/m2 twice a day on day 1 – 14, Q3W; max. 8 cycles). Primary endpoint was recurrence-free survival at 12 months (RFS@12). The trial design is based on the Simon, Wittes and Ellenberg’s Pick-the-winner design [Simon et al., 1985]. Results: 40 pts (ECOG 0 or 1) were enrolled in 12 centers in Germany: median age of 64.5 years; 53% males, 30% intra-hepatic CC, 58% extra-hepatic CC, 13% gallbladder. All pts received at least 1 dose of study treatment. The median number of cycles was 7. RFS@12 was 52.4% for arm A and 57.9% for arm B. After a median follow up of 13.8 months, median recurrence free survival was 14.98 (A) and 17.02 months (B). 1y OS rate was 85% (A) and 84% (B). While no new safety/toxicity signs were observed, arm A demonstrated a higher toxicity rate than arm B: 67% of pts having at least one grade ≥ 3 AE (A) vs. 53% (B) and 48% of pts having at least one grade ≥ 3 treatment related AE (A) vs. 32% (B). Conclusions: In the IKF/AIO-ADJUBIL trial, the expected RFS@12 of 56% was demonstrated for the combination of durvalumab / tremelimumab without capecitabine (57.9%), whereas no benefit in terms of RSF@12 was observed with additional capecitabine (52.4%). Together with similar 1y OS rates of 85% (A) and 84% (B) and higher toxicity rates in arm A, this indicates superiority of the combination of durvalumab / tremelimumab without capecitabine in pts with resectable BTC in the adjuvant setting. Clinical trial information: EU CT No.: 2024-511847-24-00 .
Source: Journal of Clinical Oncology
Authors: Thorsten Oliver Goetze, Arndt Vogel, Maria A. Gonzalez-Carmona, Timorshah Habibzada, Johanna Reinecke, Marius Adler, Daniel Pink, Thomas Jens Ettrich, Christoph Roderburg, Ursula Pession, Anna Lena Saborowski, Florian van Boemmel, Thomas Wehler, Claus-Henning Koehne, Marina Schaaf, Disorn Sookthai, Regina Eickhoff, Miriam Pons, Salah-Eddin Al-Batran, Dominik Paul Modest
Institutions: Institute of Clinical Cancer Research, Krankenhaus Nordwest, Medizinische Hochschule Hannover, University of Bonn, University Hospital Bonn, Universitätsmedizin Göttingen, University of Göttingen, University Hospital Augsburg, Universitätsmedizin Greifswald, Helios Hospital Bad Saarow, University Hospital Ulm, Düsseldorf University Hospital, University Hospital Frankfurt, University Hospital Leipzig, Universitätsklinikum Gießen und Marburg, Klinikum Oldenburg, Charité - Universitätsmedizin Berlin
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4410815624