Abstract 400TiP
Background
T-DXd is a HER2-directed antibody-drug conjugate that is approved in multiple countries for the treatment of HER2-positive and HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and HER2-mutant non-small cell lung cancer (NSCLC). In April 2024, T-DXd received accelerated approval in the US for adult pts with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors that have progressed after prior systemic treatment and have no satisfactory alternative therapies. In Part 1 of the DP-02 study (N=267), T-DXd showed clinically meaningful investigator-assessed (INV) objective response rates (ORRs; 37.1% [95% CI 31.3, 43.2]) and INV median progression-free survival (PFS; 6.9 months [95% CI 5.6, 8.0]) in pretreated pts with HER2-expressing solid tumors, with the largest effect observed in pts with centrally confirmed HER2 IHC 3+ tumors (ORR 61.3% [95% CI 49.4, 72.4]; median PFS 11.9 months [95% CI 8.2, 13.0]); safety was consistent with the known profile. Here, we describe Part 2 of the DP-02 study.
Trial design
DP-02 (NCT04482309) is an open-label, multicenter, Phase II study evaluating T-DXd (5.4 mg/kg intravenously once every 3 weeks) in pts with HER2-expressing locally advanced or metastatic solid tumors that have progressed following prior systemic treatment or have no alternative treatment options. Part 2 will enroll ∼40 pts in each of the following cohorts: A, any HER2 IHC 3+ tumor; B, any HER2 IHC 2+ / in situ hybridization–positive tumor; C, HER2 IHC 2+/1+ endometrial cancer; D, HER2 IHC 2+/1+ ovarian cancer; or E, HER2 IHC 2+/1+ cervical cancer. Pts with breast, gastric, or colorectal cancer will not be enrolled; unlike in Part 1, pts with NSCLC will be eligible for cohorts A and B. HER2 expression will be detemined by central testing and scored per ASCO/CAP gastric-specific criteria. The primary endpoint is INV confirmed ORR per RECIST 1.1. Secondary endpoints include duration of response, disease control rate, PFS, and overall survival. Safety, tolerability, pharmacokinetics, and immunogenicity will also be assessed.
Clinical trial identification
NCT04482309.
Legal entity responsible for the study
AstraZeneca and Daiichi Sankyo.
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
J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation, Regeneron; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon, Regeneron, Ascendis Pharma, Advenchen, BMS, Kelun, SUTRO; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda, GSK; Financial Interests, Institutional, Other, Sub I: Corcept. V. Makker: Financial Interests, Institutional, Funding, Study funding: Merck, Eisai, Clovis, Karyopharm, AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Financial Interests, Institutional, Funding, Study Support: BMS, Duality, Faeth, Takeda; Financial Interests, Institutional, Local PI: cullinan; Non-Financial Interests, Personal, Principal Investigator: Merck; Non-Financial Interests, Personal, Advisory Role: Eisai, Clovis, Novartis, Lilly, Gsk, Karyopharm, Iteos, Faeth, Duality, ZYmeworks, Morphosys, Moreo; Other, Personal, Other, Travel to Scientific Congress-SGO2024: AztraZeneca. A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, F. Hoffmann-La Roche, GSK, Genmab, Immunogen, Itheos, MSD, Mersana Therapeutics, Novocure, OncoXerna Therapeutics, Inc, PharmaMar, Regeneron, Sattucklabs, Seagen/Pfizer, Sutro Biopharma, Exelisis, Daiichi Sankyo, Debiopharm International, Myriad Genetics, Zentalis, TORL Therapuetics, Zymeworks; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Amgen, AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Aprea Therapeutics AB, Regeneron Pharmaceuticals, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Personal, Leadership Role, on behalf of GEICO: GCIG; Non-Financial Interests, Personal, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Personal, Leadership Role, ESMO GYN Co-Chair 2023 - 2025: ESMO; Non-Financial Interests, Personal, Leadership Role, Chair de Cervix Committee. 2022-2024: GCIG; Non-Financial Interests, Personal, Member: ESMO, ASCO, GCIG, SEOM, GOG. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono , Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. L. Jung, J. Simões, S.D. Puvvada: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, OnCusp Therapeutics, Zymeworks; Financial Interests, Personal, Other, Consulting: Calibr, Ecor1, Exelixis, GT Aperion, Infinity Pharmaceuticals, LOXO-Oncology, LegoChem Bio, Lengo Therapeutics, Tallac Therapeutics, Becton Dickinson, eFFECTOR Therapeutics, Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Incyte, Karyopharm, Protai, TheraTechnologies, Zentalis, FogPharma, Harbinger Health, Mersana Therapeutics, Sanofi Pharmaceuticals; Financial Interests, Personal, Other, Consutling: Menarini Group; Financial Interests, Personal, Advisory Board, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Invited Speaker: Dava Oncology; Financial Interests, Institutional, Other, Local PI / Research Grant: Aileron Therapeutics, Bayer Healthcare, CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., eFFECTOR Therapeutics, Taiho Pharmaceutical Co.; Financial Interests, Institutional, Other, Local PI / Research Grant / Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Calithera Biosciences, Curis Inc., Debiopharm International, Guardant Health Inc., Klus Pharma, Novartis, Jazz Pharmaceuticals, Zymeworks; Financial Interests, Institutional, Other, Local PI / Steering Committee Member: Genentech Inc.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Co., Puma Biotechnology Inc., Repare; Other, Personal, Other, Travel support: European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO); Other, Personal, Other, Travel Support: Cholangiocarcinoma Foundation, Dava Oncology. All other authors have declared no conflicts of interest.