LBA16 - Rates of pathologic complete response (pCR) after datopotamab deruxtecan (Dato) in the neoadjuvant setting: Results from the I-SPY 2.2 trial

Background

I-SPY 2.2 evaluates novel agents for breast cancer in the neoadjuvant setting in up to 3 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

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

Results

103 patients were randomized to Dato between 6/2022 and 9/2023. A total of 37 pCRs were observed: 18, 13, and 6 after Blocks A, B, and C respectively. Though numbers are small, Dato outperformed the DC in HR(-)Im(-)DRD(-) subtype. The highest rate of pCR was in (Im) subtype (59%). In a sensitivity analysis, including only those who met criteria to go to surgery, pCR rate was 67%, not statistically different from the DC. In HR(-)HER2(-) disease, 51% achieved a pCR, with a rate of 66% in the sensitivity analysis. Most common toxicities on block A were nausea, fatigue, rash. Stomatitis and ocular toxicity were less common, mostly of lower grades.

Conclusions

Dato was particularly active in the HR(-)HER2(-)Im(-)DRD(-) signature, and was safe in other subtypes, in patients who followed the treatment strategy, highlighting the importance and benefit of adherence to protocol treatment recommendations. Table: LBA16

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

J.L. Meisel: Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Genentech, Seagen, Curio Science, GSK, Olema Oncology, GE Healthcare, Pfizer; Financial Interests, Personal, Other, Travel: Pfizer, Total Health Conferencing, Puma BioTechnology; Financial Interests, Personal, Other, Honoraria: Total Health Conferencing, Medscape; Financial Interests, Personal, Research Funding: Pfizer; Financial Interests, Personal and Institutional, Research Funding: Seagen; Financial Interests, Institutional, Research Funding: Sermonix Pharmaceuticals, Olema Oncology. J. Chien: Financial Interests, Institutional, Research Funding: Merck, Puma BioTechnology, Seagen, Amgen, Pfizer. A. Wallace: Financial Interests, Personal, Speaker, Consultant, Advisor: Boston Scientific. N. Williams: Financial Interests, Personal, Other, Honoraria: NCCN, Total Health Conferencing. R. Nanda: Financial Interests, Personal, Advisory Role: Merck, Seagen, AstraZeneca, Gilead Sciences, GE Healthcare, Sanofi, Daiichi Sankyo/AstraZeneca, Exact Sciences, Guardant Health, Moderna Therapeutics, Novartis, Stemline Therapeutics; Other, Personal, Other: G1 Therapeutics; Financial Interests, Institutional, Research Funding: Corcept Therapeutics, Celgene, Merck, Seagen, Genentech/Roche, Odonate Therapeutics, Pfizer, AstraZeneca, Immunomedics, OncoSec, Arvinas, Taiho Oncology, OBI Pharma, Sun Pharma, Relay Therapeutics. V. Borges: Financial Interests, Personal, Advisory Role: Seagen, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Stocks/Shares: Perla Therapeutics; Financial Interests, Institutional, Research Funding: Seagen, Olema Oncology, AstraZeneca. E. Stringer-Reasor: Financial Interests, Personal, Advisory Role: Novartis, Eli Lilly, AstraZeneca, Merck, Seagen, Daiichi Sankyo/AstraZeneca, Pumas-AI; Financial Interests, Personal, Research Funding: Susan G. Komen for the Cure, V Foundation. J. Boughey: Financial Interests, Personal, Advisory Role: CairnSurgical, SymBioSis; Financial Interests, Personal, Other, Travel: Endomagnetics; Financial Interests, Personal, Other, Honoraria: UpToDate, PeerView, PER; Financial Interests, Institutional, Research Funding: Eli Lilly. C. Nangia: Financial Interests, Personal, Other, Honoraria: Regeneron, Eli Lilly, Gilead Sciences, Stemline Therapeutics; Financial Interests, Personal, Advisory Role: Regeneron, Eli Lilly, Gilead Sciences, Stemline Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Regeneron, Gilead Sciences, Stemline Therapeutics; Financial Interests, Personal, Other, Travel: Regeneron, Gilead Sciences, Stemline Therapeutics. C. Vaklavas: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Gilead Sciences, AstraZeneca; Other, Personal, Other: Puma Technology, Takeda, Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Guidepoint Global, Novartis, Seagen, Daiichi Sankyo/AstraZeneca, Gilead Sciences, Pfizer, Cardinal Health; Financial Interests, Institutional, Research Funding: Genentech, Roche, Pfizer, Incyte, Pharmacyclics, Novartis, TRACON Pharma, Innocrin Pharma, Zymeworks, H3 Biomedicine, AstraZeneca/Daiichi Sankyo, Seagen, AstraZeneca; Non-Financial Interests, Personal, Other: Genentech. H.S. Rugo: Financial Interests, Personal, Advisory Board, Consultancy/advisory support: Napo; Financial Interests, Personal, Invited Speaker, Honoraria: Mylan/Viatris, Chugai; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: Puma, Sanofi; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc.; Financial Interests, Institutional, Coordinating PI: OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx. L.J. Van't Veer: Financial Interests, Personal, Full or part-time Employment: Agendia; Financial Interests, Personal, Stocks or ownership: Agendia, Exai Bio. A. DeMichele: Financial Interests, Institutional, Research Funding: Pfizer, Genentech, Novartis, Inivata/NeoGenomics. N. Hylton: Financial Interests, Institutional, Research Funding: Siemens Healthineers. D. Yee: Financial Interests, Personal, Advisory Role: Martell Diagnostic; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Research Funding: Boehringer Ingelheim. C. Yau: Financial Interests, Institutional, Licencing Fees or royalty for IP: U.S. Provisional Application No. 63/314,065, U.S. Provisional Application 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.