7O - Trastuzumab deruxtecan (T-DXd) ± pertuzumab (P) in previously untreated HER2+ metastatic breast cancer (mBC): Clinical efficacy and exploratory subgroup analyses in DESTINY-Breast07

Background

DESTINY-Breast07 (NCT04538742) is a phase 1b/2 multicenter, open-label, modular study exploring the safety, tolerability, and antitumor activity of T-DXd ± other anticancer agents in HER2+ mBC. At the December 22, 2023 data cutoff (DCO), for T-DXd and T-DXd + P, cORR was 76.0% and 84.0%; 12-month PFS was 80.8% and 89.4%, respectively. By disease status, for T-DXd and T-DXd + P, cORR was 70.4% and 80.0% (recurrent) vs 79.2% and 86.7% (de novo); by hormone receptor (HR) status, cORR was 76.6% and 88.2% (HR+) vs 75.0% and 75.0% (HR−), respectively. Exploratory subgroup analyses by baseline stromal tumor-infiltrating lymphocyte (TIL) levels will be presented, including analysis of correlation between efficacy and TIL levels, a known prognostic factor in HER2+ mBC.

Methods

Patients (pts) had locally assessed HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+ / in situ hybridization +) mBC and no prior therapy for mBC; disease and HR status were assessed locally according to standard practice. Pts received T-DXd 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W) as monotherapy or with P 420 mg IV Q3W after an 840 mg loading dose. Baseline stromal TIL levels were retrospectively assessed based on International Immuno-Oncology Working Group guidelines for eligible pts with available H&E staining images.

Results

Baseline TIL levels were grouped by <20% and ≥20% of intratumoral stromal area (mean 20.5%). HR-negative tumors were enriched in pts with TIL levels ≥20% at baseline. The cORR and 12-month PFS for both groups by baseline TIL levels are given in the table. Further results from a more recent DCO are planned for presentation.

Conclusions

Encouraging clinical activity appears to be observed with T-DXd ± P in first-line HER2+ mBC, irrespective of TIL levels, similar to the outcomes observed for baseline disease characteristics. Table: 7O

Efficacy by baseline TIL levels

CI, confidence interval; cORR, confirmed overall response rate; PFS, progression-free survival

Clinical trial identification

DESTINY-Breast07 (NCT04538742).

Editorial acknowledgement

Under the guidance of authors, medical writing support was provided by Frances Singer, PhD of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

This study is sponsored by AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).

Disclosure

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. G. Fabbri: Financial Interests, Personal, Full or part-time Employment, An immediate family member is also an employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. McEwen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. T. Vaclova: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Boston, A. Konpa: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, Olema Pharmaceuticals, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Jefferies LLC, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetic Laboratories, Silverback Therapeutics, Stemline Therapeutics. S. Loi: Financial Interests, Institutional, Advisory Board, Consultant: AstraZeneca/Daiichi Sankyo, Novartis, Roche Genentech; Financial Interests, Institutional, Advisory Board, Consultant: BMS; Financial Interests, Institutional, Advisory Board, consultant: Eli Lilly, Gilead Sciences, MSD; Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca / Daiichi Sankyo, BMS, Amaroq Therapeutics, Mersana Therapeutics, Domain Therapeutics, Menari Asia-Pacific, Gilead Sciences, MSD, Roche Genentech, Bicycle Therapeutics; Financial Interests, Institutional, Funding: Novartis, BMS, MSD, Eli Lilly, Nektar Therapeutics, AstraZeneca/Daiichi Sankyo, Roche-Genentech, Gilead Sciences, Pfizer; Non-Financial Interests, Personal, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Personal, Advisory Role, consultant (not compensated): Eli Lilly, Gilead Therapeutics. C. Anders: Financial Interests, Personal, Advisory Role: Genentech/Roche, Eisai, Ipsen, Seattle Genetics, AstraZeneca, Elucida Oncology, Immunomedics, Athenex, Roche, Novartis; Financial Interests, Personal, Royalties: UptoDate.com, Jones and Bartlett; Financial Interests, Personal, Funding: Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G-1 Therapeutics, ZION, Novartis, Pfizer, Elucida Oncology, Caris, Incyclix, Beigene. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Pfizer, Roche, Gilead, Eisai, MSD, Seagen, Lilly; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Roche. R. Kim, M. Markowska: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. P. Herbolsheimer: Financial Interests, Personal, Full or part-time Employment, Employee of AstraZeneca: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Jhaveri: Financial Interests, Personal, Advisory Role: Novartis, Pfizer, AstraZeneca, Jounce Therapeutics, Synthon, Intellisphere, Bristol Myers Squibb, Genentech, AbbVie, Lilly, BluePrint Medicines, Seagen, Daiichi Sankyo, Biotheranostics, Sun Pharma Advanced Research Company, Taiho Oncology, Sanofi, Gilead Sciences, Scorpion Therapeutics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Taiho Pharmaceutical, Jounce Therapeutics, Pfizer, AstraZeneca, Intellisphere, Lilly, Gilead Sciences, Genentech/Roche; Financial Interests, Institutional, Funding: Novartis, Genentech, Debiopharm Group, ADC Therapeutics, Pfizer, Novita Pharmaceuticals, Clovis Oncology, Lilly, Zymeworks, Immunomedics, Puma Biotechnology, VelosBio/Merck, AstraZeneca, Context Therapeutics, Scorpion Therapeutics, BluePrint Medicines.