T. O. Goetze, A. Vogel, M. A. Gonzalez Carmona, T. Habibzade, J. Reinecke, M. Adler, D. Pink, T. J. Ettrich, C. Roderburg, U. Pession, A. Saborowski, F. Van Bömmel, T. C. Wehler, C.-H. Koehne, M. Schaaf, D. Sookthai, R. Eickhoff, M. Pons, S.-E. Al-Batran, D. P. Modest
- Background
Biliary tract cancer (BTC) still has a poor outcome with limited effective treatment options after curative resection. SOC is treatment with adjuvant capecitabine according to BILCAP trial, even though it was formally negative. Based on TOPAZ-1, IO combination in the adjuvant setting seems promising. The ADJUBIL trial aimed at evaluating the clinical activity of the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab +/- capecitabine in pts with resectable BTC in the adjuvant setting. 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 C1D1) 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 wasBackground
Biliary tract cancer (BTC) still has a poor outcome with limited effective treatment options after curative resection. SOC is treatment with adjuvant capecitabine according to BILCAP trial, even though it was formally negative. Based on TOPAZ-1, IO combination in the adjuvant setting seems promising. The ADJUBIL trial aimed at evaluating the clinical activity of the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab +/- capecitabine in pts with resectable BTC in the adjuvant setting. 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 C1D1) 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 a Pick-the-winner design [Simon et al., 1985].
Results
40 pts (ECOG 0/1) were enrolled in 12 centers in Germany: median age 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 RFS 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
The ADJUBIL trial was positive with the expected RFS@12 of 56% 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 durvalumab / tremelimumab without capecitabine in pts with BTC in the adjuvant setting.
Legal entity responsible for the study
Frankfurter Institut für Klinische Krebsforschung IKF GmbH.
Funding
AstraZeneca.…
