COLUMBIA-1: a randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer

Segal, NH; Tie, J; Kopetz, S; Ducreux, M; Chen, E; Dienstmann, R; Hollebecque, A; Reilley, MJ; Elez, E; Cosaert, J; Cain, J; Soo-Hoo, Y; Hewson, N; Cooper, ZA; Kumar, R; Tabernero, J

Author(s): Segal, NH; Tie, J; Kopetz, S; Ducreux, M; Chen, E; Dienstmann, R; Hollebecque, A; Reilley, MJ; Elez, E; Cosaert, J; Cain, J; Soo-Hoo, Y; Hewson, N; Cooper, ZA; Kumar, R; Tabernero, J;
Details: Publication Year 2024-10,Volume 131,Issue #6,Page 1005-1013
Journal Title: British Journal of Cancer
Publication Type: Research article
Abstract: BACKGROUND: To determine whether the addition of durvalumab (anti-PD-L1) and oleclumab (anti-CD73) to standard-of-care treatment (FOLFOX and bevacizumab) enhances the anti-tumour effect in patients with metastatic colorectal cancer (mCRC). METHODS: COLUMBIA-1 (NCT04068610) was a Phase Ib (feasibility; Part 1)/Phase II (randomised; Part 2) trial in patients with treatment-naïve microsatellite stable mCRC. Patients in Part 2 were randomised to receive standard-of-care (control arm) or standard-of-care plus durvalumab and oleclumab (experimental arm). Primary objectives included safety and efficacy. RESULTS: Seven patients were enrolled in Part 1 and 52 in Part 2 (n = 26 in each arm). Grade ≥3 treatment-emergent adverse events (TEAE) occurred in 80.8% and 65.4% of patients in the control and experimental arms of Part 2, respectively, with 26.9% and 46.3% experiencing serious TEAEs. The confirmed objective response rate (ORR) was numerically higher in the experimental arm compared with the control arm (61.5% [95% confidence interval (CI), 40.6-79.8] vs 46.2% [95% CI, 26.6-66.6]) but did not meet the statistically significant threshold in either arm. CONCLUSION: The safety profile of FOLFOX and bevacizumab in combination with durvalumab and oleclumab was manageable; however, the efficacy results do not warrant further development of this combination in patients with microsatellite stable mCRC. REGISTRATION: NCT04068610.
Publisher: Springer Nature
Keywords: Humans; *Colorectal Neoplasms/drug therapy/genetics/pathology; Female; Male; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse; effects/administration & dosage; *Bevacizumab/administration & dosage/adverse effects; Middle Aged; Aged; Adult; *Antibodies, Monoclonal/administration & dosage/adverse effects/therapeutic use; Leucovorin/administration & dosage/therapeutic use/adverse effects; Fluorouracil/administration & dosage/adverse effects; Organoplatinum Compounds/administration & dosage/adverse effects/therapeutic use; Neoplasm Metastasis; Aged, 80 and over
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1038/s41416-024-02796-3
Open Access at Publisher's Site: https://doi.org/10.1038/s41416-024-02796-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-01 07:37:03

Last Modified: 2024-10-01 07:37:20