319TiP - NeoBREASTIM: A phase II study of atezolizumab plus RP1 oncolytic immunotherapy in the neoadjuvant setting of triple-negative breast cancer (TNBC)

Background

Patients with early-stage, node-negative triple-negative breast cancer (TNBC) and risk tumor-infiltrating lymphocytes (TILs) have good prognosis, with a 5-year risk of distant relapse of <10%. Thus, chemotherapy-free modalities may be considered in these low-risk patients, sparing the significant side effects of cytotoxic chemotherapy. Antibodies targeting the programmed death-(ligand)1 (PD-(L)1) immune checkpoint have demonstrated clinical activity in TNBC. The KEYNOTE-173 study, which evaluated pembrolizumab plus chemotherapy in the neoadjuvant setting, showed that high pre- and on-treatment TILs were significantly associated with higher pathologic complete response rates. RP1 is a selectively replication competent herpes simplex virus type 1 (HSV-1), infecting preferentially human tumor cells, and a potent activator of both innate and adaptive immunity. RP1 intratumoral (IT) injection alone and combined with immune checkpoint inhibitors is safe and effective in patients with multiple solid tumors. The NeoBREASTIM study is therefore investigating the potential synergistic effect of atezolizumab combined with RP1 as neo-adjuvant, chemo-free treatment for early-stage, node-negative TNBC expressing tumor-infiltrating TILs ≥ 30%.

Trial design

The neoBREASTIM study is an open label, monocentric (Institut Curie, France), single-arm, phase II trial. Primary objective is to investigate the safety and the rate of residual cancer burden (RCB) 0-1 in patients receiving intravenous injection of atezolizumab 840 mg plus IT injection of RP1. Secondary objective includes invasive disease-free Survival 3 years after surgery. Patients with T1cN0M0 TNBC with at least 30% TILs and either detectable or undetectable circulating tumor DNA (ctDNA) at baseline will receive a window-period of three 14-day treatment cycles, after which, patients that have no increase in ctDNA will continue treatment for a total of 10 cycles prior to surgery; while, those with increase in ctDNA levels will discontinue treatment and receive standard therapy. The study aims to include 51 patients over 24 months.

Clinical trial identification

NCT06067061.

Editorial acknowledgement

Legal entity responsible for the study

Institut Curie.

Funding

Replimune Group Inc. Hoffmann La Roche provided Atezolizumab graciously.

Disclosure

D. Loirat: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Pfizer, Novartis, ExactSciences; Financial Interests, Personal, Other, Travel/congress: MSD; Financial Interests, Personal, Other, Travel/Congress: ROCHE, AstraZeneca, Gilead, Novartis; Financial Interests, Personal, Invited Speaker: Gilead, Lilly; Financial Interests, Personal, Other, Travel/Congres: Pflizer. A. Vincent-Salomon: Financial Interests, Personal, Invited Speaker, Lectures honorarium: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Ibex, Roche, PRIMAA; Financial Interests, Personal, Invited Speaker: MSD, Roche; Financial Interests, Personal, Stocks/Shares: Ibex; Financial Interests, Institutional, Research Grant: AstraZeneca, Ibex; Financial Interests, Institutional, Funding: Owkin; Financial Interests, Institutional, Research Grant, MSD Avenir research grant: MSD; Non-Financial Interests, Member of Board of Directors: RUBAN ROSE association. J. Pierga: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Seagen, MSD, Novartis, ExactSciences, Gilead, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Menarini, Veracyte, Pfizer, Lilly, Seagen, MSD, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Steering Committee Member: Novartis; Financial Interests, Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Funding: Servier. F.C. Bidard: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Novartis, AstraZeneca, GE Healthcare, SAGA Diagnostics, Daiichi Sankyo, Gilead, Inatherys; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer, Merck KGaA, Roche; Financial Interests, Institutional, Funding: Prolynx, Saga Diagnostics, Merck KGaA; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Lilly, Pfizer; Financial Interests, Personal and Institutional, Steering Committee Member: Lilly. E. Romano: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Research fundings: BMS, AstraZeneca, Amgen, Janssen, Replimune; Financial Interests, Coordinating PI: Light Chain Biosciences; Non-Financial Interests, Principal Investigator: Dragofly Therapeutics, BMS, Roche, MSD/MERCK, ImCheck Therapeutics, AstraZeneca, Pfizer. All other authors have declared no conflicts of interest.