The Phase 2 ADJUBIL Study of Durvalumab Plus Tremelimumab With or Without Capecitabine in BTC

In the ongoing phase 2 ADJUBIL study, the clinical activity of immunotherapies durvalumab and tremelimumab with or without capecitabine is being assessed in patients with resectable biliary tract cancer in the adjuvant setting.

Patients with biliary tract cancer (BTC) often have poor outcomes, and only 20% of patients with BTC are eligible for surgical resection with curative intent.¹ Patients with BTC have a 5-year overall survival of <10%, and many studies have been conducted in an effort to improve patient outcomes.¹ The British BILCAP trial established capecitabine as the standard of care for adjuvant therapy in patients with BTC; however, data are conflicting regarding whether chemotherapy is the optimal treatment in this patient population.^1,2 The results of 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 hepatocellular carcinoma. The findings provide evidence for a dual immunotherapy treatment strategy as adjuvant therapy in patients with BTC.⁴ The research design for ADJUBIL, a phase 2, open-label, randomized investigation (EudraCT number: 2021-002389-41), was presented by Thorsten Goetze, MD, at the 2023 ASCO annual meeting.¹

The ADJUBIL study aims to assess the clinical activity of durvalumab and tremelimumab with or without capecitabine in patients with resectable BTC in the adjuvant setting.

The ADJUBIL study aims 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 overall survival and the investigation of predictive biomarkers for RFS.¹ In June 2022, the first patient was enrolled in the ADJUBIL trial, and as of May 2023, 16 of 40 planned patients have been recruited. A total of 40 patients with BTC, after curative surgery and with no prior systemic anticancer 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 This trial is ongoing, and more clinical information is available at 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, 2023; 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).