Abstract 25TiP
Background
Pathological response to neoadjuvant immune checkpoint inhibitors (ICI) is associated with excellent survival in several tumor types. In Stage II-III triple negative breast cancer (TNBC), neoadjuvant anti-PD-(L)1 with chemotherapy improves pathological complete response (pCR) and reduces recurrence. In Stage I TNBC, (neo)adjuvant chemotherapy remains standard of care. Exceptional responses to ICI in TNBC have been observed, suggesting a subgroup of Stage I TNBC could be treated with ICI alone; however, biomarkers to select patients are lacking.
Trial design
POP-Durva is a prospective, single-arm phase II trial evaluating pCR after two doses of durvalumab in Stage I TNBC. Patients with untreated clinical stage I (≤2cm, N0) TNBC (ER < 10%, PR < 10%, HER-2 non-amplified) with sTIL of ≥ 5% will be included. Study treatment consists of two doses of durvalumab 10mg/kg IV, on D1 and D15. On completion of study treatment, patients will undergo breast US and will proceed to surgery, or standard neoadjuvant treatment, per physician preference. Fresh tissue biopsy and FPPE will be collected at screening, on D22 or at surgery; blood will be collected for PBMC and ctDNA at screening, D1, D15 and on D22; faecal specimen collection will occur at baseline and at end of treatment. The primary endpoint is pCR (ypT0/is ypN0). In patients who proceed directly to surgery following durvalumab, pCR will be assessed at surgery. Patients with residual invasive disease at the D22 biopsy who receive further neoadjuvant therapy will be considered non-pCR for the primary endpoint. With an expected pCR rate of 20%, a sample size of 195 patients provides a 95% confidence interval of a precision of 6.2%. Secondary objectives are ORR and safety. The key exploratory objective is to identify biomarkers of response to ICI. Spectral cytometry, single-cell RNA and TCR sequencing will be performed to describe on-treatment immune cell dynamics and to identify mechanisms of response to ICI monotherapy. Imaging-mass cytometry will characterise tumour-immune cell spatial interactions. Microbiome profiles will be correlated with response. 3 of 4 sites in France are actively recruiting; as of 05/07/2024, 22 patients have been treated.
Clinical trial identification
NCT05215106.
Legal entity responsible for the study
Gustave Roussy.
Funding
AstraZeneca.
Disclosure
J.R. Dixon Douglas: Financial Interests, Personal, Invited Speaker: Gilead Life Sciences; Other, Personal, Funding, Travel and accommodation for conference presentations: MSD; Other, Personal, Funding, Travel and accommodation for conference presentation: Pierre Fabre; Other, Personal, Funding, Travel and accommodation to attend conference: Novarits; Financial Interests, Personal, Research Grant, Stipend to fund international fellowship opporunity: Breast Cancer Trials Australia and New Zealand. E. Rassy: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Research Grant: Gilead; Non-Financial Interests, Personal, Member: ASCO, AACR; Other, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Roche, Mundipharma. O. Tredan: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis-Sandoz, Lilly, MSD, Astra-Zeneca, Pierre Fabre Oncologie, Seagen, Daiichi Sankyo, Gilead, Eisai, Stemline-Menarini, Veracyte, Exact Sciences. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: GILEAD, NOVARTIS; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: PFIZER; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Personal, Project Lead: Unicancer. L. Derosa: Financial Interests, Institutional, Advisory Board: Everimmune; Financial Interests, Institutional, Invited Speaker: BMS. F. André: Financial Interests, Personal, Advisory Board: Lilly France; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi Sankyo, Guardant Health, Owkin. S. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. All other authors have declared no conflicts of interest.