COLUMBIA-1: A phase Ib/II, open-label, randomized, multicenter study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab as first-line (1L) therapy in metastatic microsatellite-stable colorectal cancer (MSS-mCRC)

ABSTRACT

Background: Despite advances in the treatment of mCRC combining chemotherapy regimens with biologics, most patients (pts) still progress within 11 months of receiving 1L chemotherapy. Addition of novel therapies to the standard of care (SoC) to improve antitumor activity is urgently needed. The randomized part 2 of COLUMBIA-1 (NCT04068610) evaluated the safety and efficacy of combining SoC (bevacizumab [BEV] + FOLFOX) with the PD-L1 inhibitor durvalumab (D) and the anti-CD73 monoclonal antibody oleclumab (O). Method(s) Pts with previously untreated, MSS-mCRC and ECOG PS <=1 received either SoC alone or SoC + D (1500 mg, Q4W) + O (3000 mg Q2W x4 then Q4W) in the experimental arm (EXP). The primary endpoint was objective response rate (ORR) per investigator assessed RECIST v1.1. Result(s) As of 10 Dec 2021, 52 pts were enrolled, of whom 51 were response evaluable. The confirmed ORR with SoC was 44.0% (95% confidence interval [CI], 24.4-65.1%) compared to 61.5% (95% CI, 40.6-79.8%) in the EXP arm. Median OS was not reached (SoC) vs 19.1 mos (EXP);median PFS was 11.1 mos (SoC) vs 10.9 mos (EXP;Table). Grade >=3 treatment emergent adverse events (TEAEs) occurred in 76.9% of pts in SoC and 65.4% EXP. Fatal TEAEs (all unrelated) were observed in 3 pts in the EXP arm 1 with sepsis and 2 with intestinal perforation. One pt with intestinal perforation deemed related to BEV experienced fatal peritonitis. In the SoC arm, there was a single fatal COVID-19 TEAE. The most frequent treatment-related AEs in the EXP arm were diarrhea (38.5%), peripheral sensory neuropathy (38.5%) and fatigue (26.9%). There was no identified association between CD73 expression and clinical benefit. Conclusion(s) Addition of D + O to FOLFOX + BEV SoC showed a moderate response increase without PFS benefit vs SoC alone. Safety was consistent with known safety profiles. [Formula presented] Clinical trial identification NCT04068610. Editorial acknowledgement Editing support for this , under the direction of the authors, was provided by Catherine Crookes of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study AstraZeneca. Funding(s) AstraZeneca. Disclosure N.H. Segal Financial Interests, Personal, Advisory Board Immunocore, PsiOxus, Roche/Genentech, BI, Revitope, ABL Bio, Novartis, GSK, AstraZeneca, Numab;Financial Interests, Personal, Research Grant Regeneron, Immunocore, PureTech, AstraZeneca, BMS, Merck, Pfizer, Roche/Genentech. J. Tie Financial Interests, Personal, Invited Speaker, Honorarium Novartis, Amgen, Merck Serono, Merck Sharp and Dohme, Pierre Fabre;Financial Interests, Personal, Advisory Board Haystack Oncology, Amgen, Novartis, AstraZeneca, Merck Serono, Merck Sharp and Dohme, Pierre Fabre, BMS;Non-Financial Interests, Personal, Principal Investigator AstraZeneca, Pfizer, Daiichi Sankyo, Novartis. S. Kopetz Financial Interests, Personal, Ownership Interest MolecularMatch, Lutris, Iylon;Financial Interests, Personal, Research Grant Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, AstraZeneca, Novartis, Amgen, Lilly, Daiichi Sankyo;Financial Interests, Personal, Other Genetech, EMD Serono, Merck, Holy Stone, Novartis, Lilly, BI, Boston Biomedical, AstraZeneca, Bayer Health, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo, Natera, HalioDx, Lutris, Jacobio, Pfizer, Repare Therapeutics, Inivata, GSK, Jazz Pharmaceuticals, Iylon, Xilis, AbbVie, Amal Therapeutics, Gilead, Mirati, Flame Biosciences, Servier, Carina Biotechnology, Bicara Therapeutics, Endeavor BioMedicines, Numab Pharma, Johnson and Johnson/Janssen. M.P. Ducreux Financial Interests, Personal, Invited Speaker Roche, Beigene, MSD, Servier, Pierre Fabre, Amgen;Financial Interests, Personal, Advisory Board Terumo, Roche, Merck Serono, Bayer, Daiichi Sankyo, Sotio;Financial Interests, Institutional, Research Grant Keocyt, Roche, Bayer. E. Chen Financial Interests, Personal, Advisory Board AstraZeneca;Financial Interests, Personal, Princip l Investigator AstraZeneca. R. Dienstmann Financial Interests, Personal, Speaker's Bureau Roche, BI, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp and Dohme, Lilly, AstraZeneca;Financial Interests, Personal, Advisory Board Roche, BI;Financial Interests, Personal, Research Grant Merck, Pierre Fabre. A. Hollebecque Financial Interests, Personal, Invited Speaker Servier, Incyte, EISAI;Financial Interests, Personal, Advisory Board Basilea, Tahio, Relay Theraeutics, QED Therapeutics, Debiopharm;Financial Interests, Institutional, Funding: Incyte;Financial Interests, Institutional, Research Grant AstraZeneca;Non-Financial Interests, Personal, Principal Investigator, M19-345 AbbVie;Non-Financial Interests, Personal, Principal Investigator, CO42216 Roche;Non-Financial Interests, Personal, Principal Investigator, MCLA-158 Merus;Non-Financial Interests, Personal, Principal Investigator, SGNB6A Seattle Genetics;Non-Financial Interests, Personal, Principal Investigator, TAS-120-202 Tahio;Non-Financial Interests, Personal, Principal Investigator, Krystal-10 Mirati;Non-Financial Interests, Personal, Principal Investigator, ADP-0033 Adaptimmune;Non-Financial Interests, Personal, Principal Investigator, ACT16902 Sanofi;Non-Financial Interests, Personal, Principal Investigator, C4201002 Pfizer;Non-Financial Interests, Personal, Principal Investigator, RLY-4008 Relay Therapeutics;Non-Financial Interests, Personal, Principal Investigator, CC-90011 Celgene/BMS;Non-Financial Interests, Personal, Principal Investigator, Loxo-IDH Loxo/Lilly;Non-Financial Interests, Personal, Principal Investigator AstraZeneca. 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