Durvalumab Plus Tremelimumab With or Without Capecitabine in BTC: The ADJUBIL Study

Patients with biliary tract cancer (BTC) often have poor outcomes, and only 20% are eligible for surgical resection with curative intent.¹ With a 5-year overall survival of <10% in all patients with BTC, many studies have been conducted in an effort to improve patient outcomes.¹ Although results from the British BILCAP trial established capecitabine as the standard of care for adjuvant therapy in patients with BTC, data are conflicting regarding whether chemotherapy is the optimal treatment in this setting.^1,2 The TOPAZ-1 trial demonstrated an increase in overall survival when the anti–PD-L1 durvalumab was added to gemcitabine and cisplatin, adding immunotherapy as part of the frontline treatment regimen in these patients.³ In addition, the HIMALAYA trial demonstrated positive results for the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen, which consisted of a single 300-mg dose of anti-CTLA4 tremelimumab plus durvalumab 1500 mg every 4 weeks in patients with unresectable BTC. The findings provide evidence for a dual immunotherapy treatment strategy.⁴ At the 2023 ASCO annual meeting, Thorsten Goetze, MD, presented the study schema for ADJUBIL, a phase 2, open-label, randomized study of durvalumab and tremelimumab with or without capecitabine (EudraCT number: 2021-002389-41).¹

ADJUBIL researchers aim to assess the clinical activity of durvalumab and tremelimumab with or without capecitabine in patients with resectable BTC in the adjuvant setting. The primary objective of this study is to assess the antitumor activity in both groups measured by the recurrence-free survival (RFS) rate after 12 months. The secondary end points are RFS, overall survival, toxicity, and quality of life. The exploratory end points are to investigate predictive biomarkers for RFS and overall survival.¹ The first patient was enrolled in the ADJUBIL trial in June 2022, and 16 of 40 planned patients have been recruited as of May 2023. A total of 40 patients with BTC, after curative surgery and with no systemic treatment, will be enrolled and randomly assigned 1:1 to receive tremelimumab (300 mg, single dose) plus durvalumab (1500 mg every 4 weeks), with or without capecitabine (8 cycles), until disease recurrence or intolerable toxicities.¹ The trial is ongoing and more clinical information is available at https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-002389-41/DE.

References

1. Goetze T, Kochen L, Vortmeyer D, et al. A phase II study of immunotherapy with durvalumab and tremelimumab in combination with capecitabine or without capecitabine in ADJUvant situation for BILiary tract cancer (ADJUBIL). Poster presented at: ASCO 2023 Annual Meeting, June 2-6; Chicago, IL.
2. Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663-673.
3. 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).
4. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (HIMALAYA). NEJM Evid. 2022;1(8).