COLUMBIA-1: A randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer Journal Article
| Authors: | Segal, N. H.; Tie, J.; Kopetz, S.; Ducreux, M.; Chen, E.; Dienstmann, R.; Hollebecque, A.; Reilley, M. J.; Elez, E.; Cosaert, J.; Cain, J.; Soo-Hoo, Y.; Hewson, N.; Cooper, Z. A.; Kumar, R.; Tabernero, J. |
| Article Title: | COLUMBIA-1: A randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer |
| 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. © The Author(s) 2024. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; human tissue; aged; aged, 80 and over; middle aged; major clinical study; overall survival; genetics; clinical trial; constipation; fatigue; paresthesia; bevacizumab; fluorouracil; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; cancer patient; antineoplastic agent; metastasis; progression free survival; neutrophil count; phase 2 clinical trial; sensory neuropathy; nausea; randomized controlled trial; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; dehydration; peripheral neuropathy; antineoplastic activity; pathology; monoclonal antibody; abdominal pain; dyspnea; fever; pneumonia; lung embolism; colorectal neoplasms; liver metastasis; lung metastasis; antibodies, monoclonal; feasibility study; multicenter study; colorectal tumor; folinic acid; microsatellite instability; neoplasm metastasis; colitis; visceral metastasis; open study; headache; phase 1 clinical trial; platinum complex; drug therapy; oxaliplatin; colloid carcinoma; organoplatinum compounds; epistaxis; leucovorin; dysgeusia; programmed death 1 ligand 1; decreased appetite; metastatic colorectal cancer; abscess; colorectal adenocarcinoma; intestine infection; 5' nucleotidase; overall response rate; large intestine perforation; spleen metastasis; folfox protocol; very elderly; humans; human; male; female; article; median survival time; durvalumab; body temperature disorder; oleclumab |
| Journal Title: | British Journal of Cancer |
| Volume: | 131 |
| Issue: | 6 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-10-05 |
| Start Page: | 1005 |
| End Page: | 1013 |
| Language: | English |
| DOI: | 10.1038/s41416-024-02796-3 |
| PUBMED: | 39048638 |
| PROVIDER: | scopus |
| PMCID: | PMC11405658 |
| DOI/URL: | |
| Notes: | Source: Scopus |
