LBA4 - Dynamic immune compartment remodeling in response to durvalumab in the POP-DURVA study: Comprehensive Profiling using spectral cytometry and multiplex immunohistochemistry

Background

POP-DURVA (NCT05215106) is a prospective, single-arm, window of opportunity, phase II trial that evaluates the pathologic complete response rate following pre-operative PD-L1 inhibitor durvalumab monotherapy for stage I triple negative breast cancer (TNBC) with stromal tumor infiltrating lymphocytes (sTILs) > 5%. The study aims to evaluate the dynamics of the tumor-immune microenvironment (TME) following durvalumab monotherapy in patients with early-stage TNBC.

Methods

Formalin-fixed paraffin-embedded and fresh tumor biopsies were collected at baseline (Bs) and end of treatment (EOT) to capture dynamic changes within the TME. A 44-marker SC panel was used to analyze the immune cell population and their activation states, and mIHC panel (CD4, CD8, CD20, CK, CD68, CD56, FOXP3, Granzyme B and PD-1) to characterize immune-tumor cell interactions. We report the results of the first 21 pts with paired Bs and EOT SC data.

Results

Patients had a median age of 50 years (IQR: 41–65). 85% (n=18) presented an invasive, non-special type, carcinoma. 13 (62%) proceeded to surgery and 8 (38%) underwent neoadjuvant chemotherapy after end of study treatment. At Bs, mean stromal sTILs was 24%, which increased to 33% at EOT (p = 0.05). 69% of pts presented PD-L1 positive tumors (CPS ≥ 10%). Only one patient (8%) remained PD-L1 negative at EOT. Granzyme B expression increased in the TME after treatment (p = 0.01), indicating enhanced immune cell cytotoxicity. SC showed a remodelling of lymphoid and myeloid cell compartments. Marked increases in CD8+ T cells and a decrease in naïve CD4+ T cells, accompanied by a reduction in the proportion of neutrophils, were observed at EOT. Specifically, within the CD8+ compartment, in PD-1+CD39+CD103+ tissue-resident memory T cells was increased.

Conclusions

This study showed important changes in the TME, indicating activation of specific anti-tumour immunity and reduction of immune-suppressive myeloid cells in stage I TNBC. Further spatial characterisation of tumour-immune cell interactions is ongoing.

Clinical trial identification

NCT05215106.

Legal entity responsible for the study

Institut Gustave Roussy.

Funding

ARC Foundation, AstraZeneca.

Disclosure

E. Rassy: Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Institutional, Coordinating PI: MSD; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: AACR; Other, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Other, Personal, Other, Travel, Accommodations, Expenses: Roche; Other, Personal, Other, Travel, Accommodations, Expenses: Mundipharma; Other, Personal, Other, Travel, Accommodations, Expenses: Eli Lilly; Other, Personal, Other, Travel, Accommodations, Expenses: Gilead; Other, Personal, Other, Travel, Accommodations, Expenses: Novartis. O. Tredan: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis-Sandoz; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Astra-Zeneca; Financial Interests, Personal, Advisory Board: Pierre Fabre Oncologie; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Daiichi-Sankyo; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Stemline-Menarini; Financial Interests, Personal, Advisory Board: Veracyte; Financial Interests, Personal, Advisory Board: Exact Sciences. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Seagen; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Personal, Other, travel support: AstraZeneca; Financial Interests, Personal, Other, travel support: Pierre Fabre; Financial Interests, Personal, Other, travel support: MSD; Financial Interests, Personal, Other, travel support: Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Advisory Board, Advisory Board and member of Steering Committee: Olema; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Gilead; Financial Interests, Institutional, Local PI: Seagen; Financial Interests, Institutional, Local PI: MSD; Financial Interests, Institutional, Steering Committee Member: Novartis; Financial Interests, Institutional, Local PI: Novartis; Non-Financial Interests, Personal, Project Lead: Unicancer. F. André: Financial Interests, Personal, Advisory Board: Lilly France; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Owkin; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Guardant Health; Financial Interests, Institutional, Advisory Board: N-Power Medicine; Financial Interests, Institutional, Advisory Board: Servier; Financial Interests, Institutional, Advisory Board: Gilead; Financial Interests, Institutional, Advisory Board: Boston Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Owkin. All other authors have declared no conflicts of interest.