LBA15 - Rates of pathologic complete response (pCR) after datopotamab deruxtecan (Dato) plus durvalumab (Durva) treatment strategy in the neoadjuvant setting: Results from the I-SPY 2.2 trial

Background

I-SPY 2.2 evaluates novel agents for breast cancer in up to 3 neoadjuvant sequences (Blocks A/B/C) based on response predictive subtype (RPS) with the goal to achieve a pCR. RPS incorporates expression-based immune (Im), DNA repair deficiency (DRD), and luminal signatures with hormone receptor (HR) and HER2 status to classify patients into 6 subtypes.

Methods

All HER2- subtypes were eligible for Dato+Durva in Block A. Predicted responders at the end of Block A or B may go to surgery early; otherwise, they proceed to Block B +/- C. Randomization to Block B included a taxane-based regimen specific to RPS: paclitaxel +/- carboplatin +/- pembrolizumab (pembro). Patients who proceeded to Block C received doxorubicin + cyclophosphamide +/- pembro. The primary endpoint is pCR, evaluated within each RPS and HR/HER2 signature, with estimated pCR rate compared to a subtype-specific dynamic control (DC) from historical I-SPY data.

Results

106 patients were randomized to Dato + Durva between 9/2022 and 8/2023. A total of 53 pCRs were observed, with 25, 22, and 6 after Blocks A, B, and C respectively. The highest rate of pCR was seen in the Im(+) subtype (N=47), where 37 achieved pCR by end of treatment, with 20, 14, and 3 after Blocks A, B, and C respectively. In the HR(-)Im(-)DRD(-) subtype, Block A+B+C performed better than DC. Among HR-/HER2-, 39/63 achieved pCR, of which 21 were with Block A alone. The most common toxicities in Block A were nausea, stomatitis, and fatigue, predominantly at grade 1-2.

Conclusions

The Dato + Durva treatment strategy showed high rates of pCR in Im(+) subtype (79%) and HR-/HER2- (62%), with >50% of these pCRs achieved with Block A alone and > 90% after Block A+B, avoiding taxane and anthracycline treatment. Table: LBA15

Clinical trial identification

NCT01042379.

Editorial acknowledgement

Legal entity responsible for the study

Quantum Leap Healthcare Collaborative.

Funding

Quantum Leap Healthcare Collaborative, National Cancer Institute.

Disclosure

M.S. Trivedi: Financial Interests, Institutional, Research Funding: Eli Lilly, Gilead Sciences, Phoenix Molecular Designs, AstraZeneca, Regeneron, Merck, Novartis. R.A. Shatsky: Financial Interests, Personal, Advisory Role: The Dedham Group, Stemline Therapeutics, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Gilead Sciences; Financial Interests, Personal, Other, Honoraria: Curio Science, Vaniam Group, OncLive/MJH Life Sciences, IDEOlogy Health; Financial Interests, Institutional, Research Funding: Phoenix Molecular Designs, Genentech, OBI Pharma, QLHC. R. Nanda: Financial Interests, Personal, Advisory Board: AstraZeneca, BeyondSpring, Daiichi Sankyo, Exact Sciences, FujiFilm, GE, Gilead, Guardant Health, Infinity, iTeos, Merck, Moderna, Novartis, OBI, Oncosec, Pfizer, Sanofi, Seagen, Stemline; Financial Interests, Institutional, Local PI: Arvinas, AstraZeneca, Genetech/Roche, Gilead, GSK, Novartis, OncoSec, Pfizer, Relay, Seagen, Sun Pharma, Taiho; Financial Interests, Institutional, Research Grant: BMS, Corcept Therapeutics, Merck; Financial Interests, Institutional, Steering Committee Member: OBI. H.S. Rugo: Financial Interests, Personal, Advisory Role: Napo Pharmaceuticals, Puma Biotechnology, Mylan, Eisai, Daiichi Sankyo; Financial Interests, Institutional, Research Funding: OBI Pharma, Pfizer, Novartis, Eli Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Astellas Pharma, Taiho Oncology, Veru, GSK, Genentech/Roche, Stemline Therapeutics. C. Omene: Financial Interests, Personal, Other, Honoraria: Jazz. K. Kalinsky: Financial Interests, Personal, Advisory Role: Eli Lilly, Novartis, AstraZeneca, Genentech/Roche, immunomedics, Merck, Seagen, Oncosec, 4D Pharma, Daiichi Sankyo/AstraZeneca, Puma BioTechnology, Mersana, Menarini Silicon Biosystems, Myovant Sciences, Takeda, Prelude Therapeutics, RayzeBio, eFFECTOR Therapeutics, Cullinan Oncology; Other, Personal, Other: Immunomedics; Other, Institutional, Other: Genentech; Financial Interests, Institutional, Research Funding: Novartis, Genentech/Roche, Eli Lilly, Seagen, AstraZeneca, Daiichi Sankyo, Ascentage Pharma. E.T. Roussos Torres: Financial Interests, Personal, Advisory Role: Synaptical. K.S. Albain: Other, Personal, Other: Seagen; Financial Interests, Personal, Other, Honoraria: Encore Medical Education; Financial Interests, Institutional, Research Funding: Seagen, QLHC. A.S. Clark: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Board, Honoraria: Siemens; Financial Interests, Institutional, Research Funding: Novartis, Seagen, Eli Lilly. C.I. Falkson: Financial Interests, Personal, Advisory Role: Agendia, bioTheranostics; Financial Interests, Personal, Speaker’s Bureau: OncLive/MJH Life Sciences; Financial Interests, Personal, Other, Honoraria: Curio Science; Financial Interests, Institutional, Research Funding: Oncolytics, QLHC, Eli Lilly. C. Isaacs: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Puma Biotechnology, Seagen, Ion Solutions, AstraZeneca/MedImmune, Gilead Sciences; Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Personal, Royalties: McGraw Hill Publishing, UpToDate, Elsevier; Other, Personal, Other: Side-Out Foundation, MJH/PER, Curio/Vaniam Group, Medscape; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Institutional, Research Funding: Tesaro, Merck, Seagen, Pfizer, GSK, AstraZeneca, Novartis, Genentech/Roche, Bristol Myers Squibb/Celgene. A. Thomas: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Stocks or ownership: Gilead Sciences, Bristol Myers Squibb, Pfizer, Doximity; Financial Interests, Institutional, Research Funding: Sanofi, Merck. J. Tseng: Financial Interests, Personal, Other, Travel: Stryker, Elucent Medical, Intuitive Surgical; Financial Interests, Institutional, Research Funding: Intuitive Surgical. L.J. Van't Veer: Financial Interests, Personal, Full or part-time Employment: Agendia; Financial Interests, Personal, Stocks or ownership: Agendia, Exai Bio. N. Hylton: Financial Interests, Institutional, Research Funding: Siemens Healthineers. D. Yee: Financial Interests, Personal, Advisory Board: Martell Diagnostic; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Research Funding: Boehringer Ingelheim. C. Yau: Financial Interests, Institutional, Royalties: No. 63/314,065, No. 63/341,579. L. Esserman: Financial Interests, Personal, Advisory Role: Blue Cross Blue Shield Association; Financial Interests, Personal, Other, Travel: Blue Cross Blue Shield Association; Financial Interests, Institutional, Research Funding: Moderna Therapeutics; Non-Financial Interests, Personal, Other: QLHC. All other authors have declared no conflicts of interest.