Abstract 160P
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).
Methods
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.
Results
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.
Conclusions
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. Table: 160P
| RECIST v1.1 | ||
| Response Evaluable Population | ||
| SoC (n=25) | EXP (n=26) | |
| Best Overall Response, n (%) | ||
| Confirmed CR | 0 | 1 (3.8) |
| Confirmed PR | 11 (44.0) | 15 (57.7) |
| SD | 12 (48.0) | 7 (26.9) |
| Unconfirmed PR | 3 (12.0) | 1 (3.8) |
| PD | 1 (4.0) | 2 (7.7) |
| Unknown/not evaluable | 1 (4.0) | 1 (3.8) |
| ORR, n (%) [95% CI %] | 11 (44) [24.4, 65.1] | 16 (61.5) [40.6, 79.8] |
| Disease Control, n (%) [95% CI %] | 23 (92.0) [74.0, 99.0] | 23 (88.5) [69.8, 97.6] |
| Median DoR, mos (95% CI %) | 7.6 (3.7, NE) | 10.3 (5.8, 14.9) |
| Median PFS, mos (95% CI %)** | 11.1 (7.3, 19.3) | 10.9 (6.9, 15.1) |
| PFS rate at 12 mos, % (95% CI %)** | 35.9 (16.2, 56.2) | 36.1 (17.1, 55.5) |
| Median OS, mos (95% CI %)** | NR (18.2, NE) | 19.1 (10.6, NE) |
*NE=Not Estimable; **ITT Population: SoC (n=26), EXP (n=26)
Clinical trial identification
NCT04068610.
Editorial acknowledgement
Editing support for this abstract, 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
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, Principal 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. M. Reilley: Financial Interests, Personal, Advisory Board: BMS, Helsinn, ZielBio. M.E. Elez Fernandez: Financial Interests, Personal, Invited Speaker: Novartis, Organon; Financial Interests, Personal, Advisory Board: Amgen, Bayer, F. Hoffman La Roche, Merck Serono, MSD, Pierre Fabre, Sanofi, Servier; Financial Interests, Institutional, Funding: Amgen, Array Biopharma, AstraZeneca, BeiGene, BI, BMS, Celgene, Debiopharm International SA, F. Hoffman La Roche, Genentech, HalioDX SAS, Hutchinson MediPharma International, Janssen-Cilag SA, Menarini, Merck Health KgaA, MSD, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, PharmaMar, Sanofi Aventis Recherche & Developpement, Servier, Taiho Pharma; Financial Interests, Personal, Other, ASCO Scientific Program Committee: Developmental Therapeutics – Immunotherapy: ASCO; Financial Interests, Personal, Other, Speaker of the ESMO Academy: ESMO; Financial Interests, Personal, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: SEOM; Financial Interests, Personal, Other, Travel, accommodations, expenses: Amgen, Array BioPharma, BMS, Merck Serono, Roche, Sanofi, Servier. J. Cosaert: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Member: AstraZeneca. J. Cain: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Hernandez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Hewson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Z.A. Cooper: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Dressman: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Tabernero: Financial Interests, Personal, Advisory Role: Array BioPharma, AstraZeneca, Bayer, BI, Chugai, Daiichi Sankyo, F. 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