LBA10 - Primary endpoint results of the Neo-CheckRay phase II trial evaluating stereotactic body radiation therapy (SBRT) +/- durvalumab (durva) +/- oleclumab (ole) combined with neo-adjuvant chemotherapy (NACT) for early-stage, high risk ER+/HER2- breast cancer (BC)

Background

Combining SBRT with a PD-L1 inhibitor and an adenosine-targeting agent (ole, anti-CD73) may potentiate anti-tumour immunity and response to NACT in high-risk early-stage luminal BC. Neo-CheckRay (NCT03875573) is the first prospective, international, phase 2, randomized trial investigating this treatment.

Methods

Eligible patients (pts) with newly diagnosed cT1c-3 (≥ 2 cm) cN0 or cT1c-3 (≥ 1.5 cm) cN1-3, grade 2 (Ki67 ≥ 15%) or grade 3, MammaPrint (MP) high risk, invasive ER+/HER2- BC were randomized 1:1:1 to arm 1: neo-adjuvant paclitaxel q1w x12 with SBRT at week 5 (3x8 Gy targeting the primary tumour, avoiding lymph nodes and normal breast tissue), followed by dose-dense epirubicin/cyclophosphamide q2w x4; arm 2: arm 1 + durva 1500mg q4w x5; and arm 3: arm 2 + ole 3000 mg q2w x4 then q4w x3. Stratification factors included tumour PD-L1 status, nodal involvement and tumour size. Accrual target was 132 pts. Primary endpoint is residual cancer burden (RCB) 0 -1 rates. Secondary endpoints include pathological complete response (pCR; ypT0/Tis ypN0) rate, adverse event (AE) and death incidences. After surgery, pts received standard radiation therapy (without tumour bed boost) and adjuvant endocrine therapy.

Results

147 pts were randomized, 9 were MP low risk and 135 are evaluable for the ITT analysis. At the time of abstract preparation, among the 135 pts, 133 pts had undergone surgery; 2 results at surgery in arm 2 are pending but will be presented at the conference (table). There were no grade 3/4 AE related to SBRT and there were no deaths. Table: LBA10

Conclusions

The addition of durva+/- ole numerically increases pCR and RCB 0/1 rates compared to NACT+SBRT. Final statistical analysis will be presented at the conference. Ongoing translational research will shed light on the mechanisms of response.

Clinical trial identification

EudraCT 2018-004165-13, NCT03875573.

Editorial acknowledgement

Legal entity responsible for the study

Institut Jules Bordet, Brussels, Belgium.

Funding

AstraZeneca and Agendia.

Disclosure

A. De Caluwe: Financial Interests, Institutional, Research Funding: AstraZeneca; Non-Financial Interests, Personal, Member: EORTC, BSMO, ESTRO. E. Agostinetto: Financial Interests, Personal, Invited Speaker: Eli Lilly, AstraZeneca; Financial Interests, Personal, Writing Engagement: Sandoz; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Gilead. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, BMS, Exact Sciences, Daichhi Sankyo, AstraZeneca; Financial Interests, Personal, Invited Speaker: Daichii Sankyo, AstraZeneca; Financial Interests, Personal, Funding, Roche funded personally the assessment of immune-markers in a research study. This was in 2019: Roche; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Funding: Puma Biotechnology. C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Vertex, Seattle Genetics, Amgen, INC, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid, Puma; Financial Interests, Personal, Invited Speaker: Eisai, Prime oncology, Teva; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Institutional, Other, Internal speaker: Genentech; Financial Interests, Personal, Other, Regional speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Personal, Advisory Board, Stock options: Signatur Biosciences. M. Piccart: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, MSD, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Menarini, Seattle Genetics, Seagen, Gilead, NBE Therapeutics, Frame Therapeutics; Financial Interests, Personal, Advisory Board, Consultant and invited speaker: Roche-Genentech; Financial Interests, Personal, Member of Board of Directors, Scientific Board: Oncolytics; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Gilead; Financial Interests, Institutional, Funding: Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. M. Ignatiadis: Financial Interests, Personal, Invited Speaker: Novartis, Daichi, Menarini Group; Financial Interests, Personal, Other, Independent monitoring committee: Seattle Genetics; Financial Interests, Personal, Other, Grants review: Gilead Sciences; Financial Interests, Personal, Other, consultant: Rejuveron Senescence Therapeutics; Financial Interests, Institutional, Other, travel grants: AstraZeneca; Financial Interests, Institutional, Coordinating PI: Pfizer, Roche, Natera, Inivata Inc; Non-Financial Interests, Officer: EORTC. 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. L. Buisseret: Financial Interests, Institutional, Advisory Board: Domain Therapeutics; Financial Interests, Institutional, Other, Steering Committee: iTeos Therapeutics; Financial Interests, Personal, Other, writing of clinical cases: Mirrors of Medicine; Financial Interests, Institutional, Other, Travel grant: GILEAD; Financial Interests, Institutional, Other, travel grant: AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant for an investigator initiated trial: Astra Zenaca; Non-Financial Interests, Principal Investigator: iTeos Therapeutics; Non-Financial Interests, Member, Member of the Breast Group and IMMUcan consortium: EORTC; Non-Financial Interests, Member: BSMO, ASCO. All other authors have declared no conflicts of interest.