LBA17 - Primary endpoint results of SYNERGY, a randomized phase II trial, first-line chemo-immunotherapy trial of durvalumab, paclitaxel, and carboplatin with or without the anti-CD73 antibody oleclumab in patients with advanced or metastatic triple-negative breast cancer (TNBC)

Background

Overexpression of the ectoenzyme CD73 is involved in the generation of immunosuppressive adenosine in the tumor microenvironment and is associated with poor prognosis in patients (pts) with TNBC. Blocking CD73 with oleclumab may enhance the antitumor response to the combination of an anti-PD-L1 with chemotherapy in TNBC.

Methods

Women with previously untreated, inoperable locally advanced or metastatic TNBC were randomized to weekly carboplatin (AUC 1.5) and paclitaxel (80 mg/m2) x12 combined with durvalumab (1500 mg q4w) with (Arm A) or without (Arm B) oleclumab (3000 mg q2w x5 then 3000 mg q4w) in 16 centers in France and Belgium. Maintenance with durvalumab +/- oleclumab was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Pts were stratified by PD-L1 and CD73 IHC expression assessed on baseline tumor tissue. The primary endpoint was clinical benefit rate (CBR; complete/partial response and stable disease according to RECIST 1.1) at week 24. A prespecified interim analysis was planned after CB assessment of the first 34 evaluable pts per arm.

Results

127 pts were recruited and assessed for eligibility (63 in arm A, 64 in arm B) between June 2019 and June 2021 when the recruitment was stopped due to the results of the interim analysis that crossed the futility boundary. Pts under treatment were allowed to continue with durvalumab+/-oleclumab. At data cutoff (July 4, 2022), the median follow-up was 13.2 months with a CBR of 42.9% in arm A and 43.3% in arm B (one-sided Fisher's exact, p=0.61) with no significant difference according to PD-L1 or CD73 status. PFS was not significantly different among arms: median PFS 6 months in arm A vs. 7.7 months in arm B, one-sided log rank test, p=0.89. The safety profile was similar in both arms. 9 patients in each arm are still under immunotherapy maintenance.

Conclusions

The addition of oleclumab to durvalumab with carboplatin/paclitaxel did not increase CBR at week 24 in first-line advanced TNBC. Ongoing translational research aims to better understand the mechanisms of responses to the study combination.

Clinical trial identification

Sponsor Protocol Number: IJB-SYNERGY-012017, Issue date 30/06/2018.

Editorial acknowledgement

Legal entity responsible for the study

Institut Jules Bordet, Brussels, Belgium.

Funding

AstraZeneca/MedImmune.

Disclosure

L. Buisseret: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Funding: Fondation Contre le Cancer. D. Loirat: Financial Interests, Personal, Advisory Board, Honoraria: AstraZeneca, Eli Lilly, Immunomedics, MSD, Pfizer, Roche, 4D Pharma, Daiichi Sankyo, Novartis, Gilead; Financial Interests, Personal, Royalties, Travel support: Pfizer, Roche, MSD, AstraZeneca. P.G. Aftimos: Financial Interests, Personal, Advisory Board, Consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte; Financial Interests, Personal, Advisory Board, Honoraria: Synthon, Amgen, Novartis, Gilead; Financial Interests, Personal, Royalties, Travel support: Amgen, MSD, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Roche. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Roche, Vifor Pharma, Eli Lilly, Pierre Fabre, McCann Health, Roularta, Teva, Gilead Sciences, Pfizer, Gilead, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Novartis, Eli Lilly, Mundi Pharma, MSD, Medscape, MSD; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Gilead, Novartis, MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Sanofi; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium; Non-Financial Interests, Advisory Role, External Scientific Advisor: European Medicine Agency. C. Maurer: Financial Interests, Personal, Royalties, Travel support: Mundipharma, Amgen, Servier Deutschland GmbH, AbbVie; Financial Interests, Personal, Advisory Board, Honoraria: AbbVie; Financial Interests, Personal, Advisory Board: Celgene/ BMS. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: AstraZeneca, Pierre Fabre, Roche, Amgen, Servier, Sanofi, MSD, BMS. D. Taylor: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Medscape, Roche, Novartis, Agendia, MSD; Financial Interests, Personal, Royalties: Pfizer, Roche, AstraZeneca . F. Clatot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Roche, Merck, BMS, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche; Financial Interests, Personal, Royalties: AstraZeneca, Roche, Eli Lilly, Merck, BMS, MSD, Pfizer . T.F.A. van den Mooter: Financial Interests, Personal, Advisory Board: Pfizer, Astellas, Bayer, MSD; Financial Interests, Personal, Royalties: Roche, Merck, Pfizer. J. Canon: Financial Interests, Personal, Advisory Board: Lilly, Roche, Pfizer, BMS, Daiichi; Financial Interests, Institutional, Research Grant: Roche, BMS, Amgen. F.P. Duhoux: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, Gilead, Novartis, Pfizer, Pierre Fabre, Roche and Seagen, Amgen, AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Pierre Fabre, Roche and Seagen, Gilead; Financial Interests, Personal, Royalties: Amgen, Pfizer, Roche, Teva. F. Bazan: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, AstraZeneca, Clovis, SeaGen, Daiichi Sankyo. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis; Financial Interests, Personal, Invited Speaker: Seattle Genetic, Zodiac, Libbs, Pierre Fabre; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE. M. Ignatiadis: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Independent monitoring committee: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Natera; Non-Financial Interests, Invited Speaker: EORTC; Non-Financial Interests, Officer: EORTC. M. Piccart: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, MSD, Novartis, Pfizer; Financial Interests, Personal, Other, Consultant: Camel-IDS/Precirix; Financial Interests, Personal, Advisory Board: Immunomedics, Menarini, Odonate, Seattle Genetics, Immutep, SeaGen, Gilead, NBE Therapeutics, Frame Therapeutics; Financial Interests, Personal, Advisory Board, Consultant and invited speaker: Roche-Genentech; Financial Interests, Personal, Invited Speaker, Scientific Board: Oncolytics; Financial Interests, Institutional, Research Grant: AstraZeneca, Immunomedics, Lilly; Financial Interests, Institutional, Funding: Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. All other authors have declared no conflicts of interest.