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.

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 .