Faculty, Staff and Student Publications

Publication Date

10-1-2024

Journal

British Journal of Cancer

DOI

10.1038/s41416-024-02796-3

PMID

39048638

PMCID

PMC11405658

PubMedCentral® Posted Date

7-25-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Colorectal Neoplasms, Female, Male, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Middle Aged, Aged, Adult, Antibodies, Monoclonal, Leucovorin, Fluorouracil, Organoplatinum Compounds, Neoplasm Metastasis, Aged, 80 and over

Comments

Registration: NCT04068610.

Published Open-Access

yes

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