Abstract 185P
Background
DEBBRAH, ROSET-BM, TUXEDO-1, and a pooled DB-01, -02, -03 analysis indicate robust efficacy of T-DXd in pts with stable/active BM; however, efficacy in pts with BM is not yet fully established. DB-07 is a phase Ib/II, multicenter, open-label study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). Results are from an interim analysis of the dose-expansion phase of T-DXd monotherapy in pts with active BM.
Methods
Pts had locally assessed HER2+ mBC with measurable disease. No or one prior line of therapy for mBC was allowed; a disease-free interval of ≥12 months from (neo)adjuvant HER2-directed therapy or chemotherapy was required. Pts had untreated BM not requiring local therapy or progressing BM after treatment with local therapy. Ongoing use of systemic corticosteroids (>2 mg dexamethasone daily or equivalent) for control of BM symptoms was exclusionary. Pts received T-DXd 5.4 mg/kg intravenously every 3 weeks. Primary endpoints were safety and tolerability; secondary endpoints included objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1 and Response Assessment in Neuro-Oncology (RANO)-BM.
Results
Thirty-five pts with active BM were treated (median age 49 years); median follow up was 11.5 months (range 5.3–24.6). As of August 1, 2023, the most common any-grade adverse events (AEs) were nausea (74.3%; Grade 3, 5.7%) and vomiting (45.7%; Grade 3, 2.9%); no Grade ≥4 nausea or vomiting was reported. By RANO-BM, confirmed ORR was 57.1% and PFS rate at 12 months was 74.6% (Table).
Conclusions
The safety profile is consistent with the known profile for T-DXd and data confirm promising efficacy in pts with active BM; a median PFS has not been reached after 11.5 months. Ongoing analyses will provide more mature data. Table: 185P
Key safety and efficacy data
| T-DXd in pts with active BM (n=35) | ||
| Any-grade AEs, n (%) | 35 (100) | |
| AEs Grade ≥3, n (%) | 18 (51.4) | |
| Serious AEs, n (%) | 5 (14.3) | |
| Any-grade pneumonitis (adjudicated as interstitial lung disease related to study drug), n (%) | 3 (8.6) | |
| Grade 2, n (%) | 2 (5.7) | |
| Grade 5, n (%) | 1 (2.9) | |
| Median actual treatment duration, months (range) | 10.0 (2.6–24.3) | |
| Overall response (RECIST 1.1 by investigator) | Intracranial response (RANO-BM BICR) | |
| Confirmed ORR, % (80% CI) | 77.1 (65.5, 86.2) | 57.1 (44.9, 68.7) |
| PFS rate at 12 months, % (80% CI) | 84.5 (74.1, 91.0) | 74.6 (59.4, 84.8) |
BICR, blinded independent central review; CI, confidence interval.
Clinical trial identification
NCT04538742.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Katie Ryding, PhD, of Helios Medical Communications.
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
C. Anders: Financial Interests, Personal, Advisory Role: Genentech/Roche, Eisai, Ipsen, Seagen, AstraZeneca, Elucida Oncology, Immunomedics, Athenex, Roche; Financial Interests, Personal, Other, Expenses: Eisai; Financial Interests, Personal, Royalties: Up to Date.com, Jones and Bartlett; Financial Interests, Personal, Other, Honoraria: Eisai, Genentech/Roche, IPSEN, Seagen, Puma Biotechnology, AstraZeneca, Elucida Oncology, Immunomedics, Athenex, Novartis; Financial Interests, Institutional, Funding: Puma Biotechnology, Lilly, Merck, Nektar, Tesaro, Seagen, G1 Therapeutics, Pfizer, Zion Pharma, Novartis Pharmaceuticals UK Ltd., AstraZeneca, Caris Life Sciences, Elucida Oncology, Roche. S. Loi: Financial Interests, Institutional, Advisory Role: Roche/Genentech, Aduro Biotech, Novartis, G1 Therapeutics, PUMA Biotechnology, GSK, AstraZeneca, Seagen, Bristol Myers Squibb, Silverback Therapeutics, Pfizer, Gilead Sciences, Daiichi Sankyo/Lilly, Tallac Therapeutics; Financial Interests, Personal, Other, Travel/Expenses: Bristol Myers Squibb; Non-Financial Interests, Personal, Writing Engagements: Roche Medical writing support; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, Novartis, MSD Oncology, Mersana; Financial Interests, Institutional, Funding: Roche/Genentech, Novartis, Merck, Puma Biotechnology, Bristol Myers Squibb, Seagen, AstraZeneca, Nektar, Lilly. E.P. Hamilton: Financial Interests, Institutional, Advisory Role: Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Greenwich LifeSciences, Orum Therapeutics, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis GmbH, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Zentalis; Financial Interests, Institutional, Funding: AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRX, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millennium, TapImmune Inc., Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, AbbVie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceutical, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Sutro Biopharma, Zenith Epigenetics, Arvinas, Harpoon, Black Diamond Therapeutics, Orinove, Molecular Templates, Seagen, Compugen, G1 Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Onconova Therapeutics, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akeso Biopharma, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repertoire Immune Medicines, Treadwell Therapeutics, Jacobio, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, ProfoundBio, Cullinan Oncology, Bristol Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics. K. Jhaveri: Financial Interests, Personal, Advisory Role: AbbVie Inc., AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo Inc., Eisai Inc; Financial Interests, Institutional, Funding: AstraZeneca, Debiopharm, Genentech, Gilead Sciences Inc., Loxo Oncology Inc. P. Schmid: Financial Interests, Personal, Full or part-time Employment, An Immediate Family Member: Roche; Financial Interests, Personal, Advisory Role, An Immediate Family Member: Genentech/Roche; Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, Boehringer Ingelheim, Bayer, Pfizer, Novartis, Eisai, Celgene, Puma Biotechnology; Financial Interests, Personal, Other, Travel/Expenses: ESMO, SABCS; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma Biotechnology, Roche, Eisai, Celgene, Bayer, Gilead Sciences Hong Kong, Sanofi, Stemline Therapeutics, Celgene; Financial Interests, Institutional, Other, Honoraria: Genentech, Oncogenex; Financial Interests, Institutional, Funding: AstraZeneca, Astellas Pharma, Oncogenex, Genentech, Novartis, Roche, Medivation. E. Gokmen: Financial Interests, Personal, Stocks/Shares: Immunogen, Macrogenics; Financial Interests, Personal, Other, Honoraria: Eli Lilly, Roche, Pfizer, Novartis, Janssen Oncology, Astellas Pharma, Amgen, AstraZeneca, Bristol Myers Squibb/Celgene, Gilead Sciences, Sandoz-Novartis, Abdi Ibrahim, MSD Oncology, Genekor; Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Lilly, MSD Oncology, Gilead Sciences, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, Novartis, Lilly, Bristol Myers Squibb/Celgene, Genekor, AstraZeneca; Financial Interests, Personal, Other, Travel/Expenses: Pfizer, Roche, MSD Oncology, Novartis, BMS. S. Im: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis, Roche/Genentech, Eisai, Pfizer, Amgen, Hanmi, Lilly, MSD, Daiichi Sankyo; Financial Interests, Personal, Other: Roche; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Daewoong Pharmaceutical, Eisai, Boryung Pharmaceuticals. C.H. Barrios: Financial Interests, Institutional, Research Grant: Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, GSK, Janssen, OBI Pharma, Lilly, Seagen, Roche, BMS, MSD, AstraZeneca, Novocure, Aveo Oncology, Takeda, PharmaMar, Gilead Sciences, Servier, Tolmar, Nanobiotix, Dizal Pharma; Non-Financial Interests, Personal, Other, CRO: TRIO, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, Worldwide, Latinaba, Fortrea, PPD, Syneos Health; Financial Interests, Personal, Stocks/Shares: Tummi, MEDSir; Financial Interests, Personal, Advisory Board: GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, Daiichi Sankyo. Y.H. Park: Financial Interests, Personal, Advisory Role: Pfizer, Roche, Eisai, Daiichi Sankyo, AstraZeneca, MSD, Novartis, Lilly, Menarini, Gilead Sciences, Boryung; Financial Interests, Personal, Other, Travel/Expenses: Gilad; Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer, Roche, Lilly, AstraZeneca, MSD, Eisai, Daiichi Sankyo; Financial Interests, Personal, Funding: AstraZeneca, Pfizer; Financial Interests, Institutional, Funding: Roche, Gencurix, Genome Insight, NGeneBio. S. Boston: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Other, Travel/Expenses: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Konpa: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Mondal: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. F. André: Financial Interests, Institutional, Advisory Role: Guardant Health, AstraZeneca, Daiichi Sankyo, Roche, Pfizer, Owkin, Novartis, N-Power Medicine, Servier, Gilead Sciences, Boston Pharmaceuticals; Financial Interests, Personal and Institutional, Advisory Role: Lilly; Financial Interests, Personal, Other, Travel/Expenses: Novartis, Roche, GSK, AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca, Novartis, Pfizer, Lilly, Roche, Daiichi Sankyo, Owkin, Guardant Health. All other authors have declared no conflicts of interest.