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

Br J Cancer. 2024 Oct;131(6):1005-1013. doi: 10.1038/s41416-024-02796-3. Epub 2024 Jul 25.

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.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal* / administration & dosage
  • Antibodies, Monoclonal* / adverse effects
  • Antibodies, Monoclonal* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use

Substances

  • Bevacizumab
  • Antibodies, Monoclonal
  • durvalumab
  • Leucovorin
  • Fluorouracil
  • Organoplatinum Compounds

Supplementary concepts

  • Folfox protocol

Associated data

  • ClinicalTrials.gov/NCT04068610