2O - TILs and PD-L1 early dynamics in the randomized Neo-CheckRay phase II trial evaluating neo-adjuvant immuno-radiation and adenosine pathway blockade for early-stage, high risk ER+/HER2- breast cancer (BC)

Background

Neo-CheckRay (NCT03875573) demonstrated high rates of pathological complete response (pCR) after immune-modulating stereotactic body radiation therapy (iSBRT) to the primary BC in combination with the anti-PD-L1 durvalumab (durva) in high-risk early-stage luminal BC. The novel regimen demonstrated most benefit in the PD-L1 negative subgroup. Here, we compare stromal TILs and PD-L1 and at baseline and at week 6 (W6) (= 1 week after iSBRT) with pCR rate at surgery (week 21-25) across the 3 treatment arms.

Methods

Eligible patients (pts) were MammaPrint® high risk and stage cT1c-3cN0-3. Pts were randomized 1:1:1 to ARM 1: paclitaxel q1w x12 with iSBRT at week 4 (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 q4w x5; and ARM 3 : arm 1 + durva + oleclumab (anti-CD73) q2w x4 then q4w x3. FFPE biopsies were taken at baseline and at W6 for assessment of PD-L1 and TILs. PD-L1 IHC status was assessed using the SP263 assay on immune cells (IC), tumor cells (TC) and using the combined positive score (CPS). TILs or PD-L1 increase was defined by an absolute change of ≥ 1 %.

Results

Baseline TILs > 1% were observed in 51.5% of pts and this proportion decreased in the 3 arms at W6. Baseline PD-L1 IC > 1% was observed in 57.0% of pts and this proportion increased in the 3 arms at W6, with a more pronounced increase in the two arms with durva (Arm 2 and 3). In 32.2% of pts, there was no tumor at W6. Increase of PD-L1 at W6 and absence of tumor at W6 were associated with a higher rate of pCR at surgery, particularly in the arms with durva. Table: 2O

B, baseline; pts, patients; W6, week 6. *Stratification factor.

Conclusions

In pts treated with iSBRT+durva, PD-L1 increase or absence of tumor at W6 is associated with higher pCR rate at surgery.

Clinical trial identification

NCT03875573.

Legal entity responsible for the study

Jules Bordet Institute.

Funding

AstraZeneca and Agendia.

Disclosure

A. De Caluwé: Financial Interests, Institutional, Trial Chair: AstraZeneca. E. Romano: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Research fundings: BMS, AstraZeneca, Amgen, Janssen, Replimune; Financial Interests, Personal, Coordinating PI: Light Chain Biosciences; Non-Financial Interests, Personal, Principal Investigator: Dragofly Therapeutics, BMS, Roche, MSD/Merck, ImCheck Therapeutics, AstraZeneca, Pfizer. C. Van Marcke: Financial Interests, Institutional, Advisory Board: Eli Lilly, Novartis, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Merck; Non-Financial Interests, Personal, Member of Board of Directors: BSMO. M. Ignatiadis: Financial Interests, Personal, Other, Consultant: 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, Personal, Officer: EORTC. 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. J. Stagg: Financial Interests, Personal, Advisory Board: Coherus Biosciences, Domain Therapeutics, Ability Biologics, Skymab; Financial Interests, Personal, Financially compensated role: MisoChip. C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Seattle Genetics, Amgen, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: Prime oncology; Financial Interests, Personal, Advisory Board, Stock options: Signatur Biosciences; Financial Interests, Personal, Stocks/Shares, Stock: Signatur Biosciences. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, BMS, Exact Sciences, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi 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. 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: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: iTeos Therapeutics; Non-Financial Interests, Personal, Member, Member of the Breast Group and IMMUcan consortium: EORTC; Non-Financial Interests, Personal, Member: BSMO, ASCO. All other authors have declared no conflicts of interest.