74MO - Trastuzumab deruxtecan (T-DXd) for pretreated patients (pts) with HER2-expressing solid tumors: Primary analysis from the DESTINY-PanTumor02 (DP-02) study

Background

T-DXd has shown significant survival benefit for pts with HER2-expressing breast and gastric cancers. Interim DP-02 data showed a promising objective response rate (ORR) and duration of response (DOR) in HER2-expressing tumors (ASCO 2023). Here we report the primary analysis including progression-free (PFS) and overall survival (OS).

Methods

This open-label, phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in pts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing), locally advanced/metastatic disease after ≥1 systemic treatment (Tx), or without alternative Tx options. Primary endpoint was investigator-assessed confirmed ORR. Secondary endpoints included safety, DOR, PFS and OS.

Results

At data cut off (Jun 2023), 267 pts with biliary tract (BTC), bladder (URO), cervical (CC), endometrial (EC), ovarian (OC), pancreatic (PC), or other tumors had received Tx (median [m] follow up: 12.75 [range 0.4–31.6] months [mo]); 72.3% received ≥2 prior lines of therapy. In all pts, investigator-assessed ORR (95% CI) was 37.1% (31.3, 43.2); mDOR (95% CI) was 11.3 mo (9.6, 17.8); mPFS (95% CI) was 6.9 mo (5.6, 8.0); and mOS (95% CI) was 13.4 mo (11.9, 15.5). In pts with IHC 3+ expression (central; n=75) ORR was 61.3% (49.4, 72.4); mDOR was 22.1 mo (9.6, not reached); mPFS was 11.9 mo (8.2, 13.0); and mOS was 21.1 mo (15.3, 29.6). The table shows ORR, PFS and OS by tumor type in all pts and IHC 3+. Grade (G) ≥3 Tx-related adverse events (AEs) occurred in 40.8% of pts; 8.6% discontinued Tx due to Tx-related AEs. Adjudicated Tx-related interstitial lung disease/pneumonitis occurred in 10.5% (n=28) of pts (9.0% [n=24] G≤2; 1.1% [n=3] G5).

Conclusions

We observed durable responses to T-DXd and clinically meaningful PFS and OS in pretreated pts across HER2-expressing tumors, with safety consistent with the known profile. These data support T-DXd as a potential tumor-agnostic treatment in HER2-expressing tumors. Table: 74MO

NR, not reached

Clinical trial identification

NCT04482309.

Editorial acknowledgement

Under the guidance of authors and in accordance with GPP3, medical writing and editorial support was provided by Melanie Francis, MSc, of Helios Medical Communications.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

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; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, F. Hoffman-La Roche Ltd., Zymeworks, OnCusp Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Advisory Board: Zentalis, Karyopharm, Biovica, Eisai, Protai, TheraTechnologies; Financial Interests, Personal, Other, Consulting: Tallac Therapeutics, Lengo Therapeutics, LOXO-Oncology, Black Diamond, Infinity Pharmaceuticals, AbbVie, GT Aperion, Ecor1; Financial Interests, Personal, Other, Consutling: Menarini Group; 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; 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. 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; 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. A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, EMD Serono, Eisai, F. Hoffmann-La Roche, GSK, Genmab, Immunogen, Itheos, Merck Sharps & Dohme de España, SA, Mersana Therapeutics, Novocure, OncXerna Therapeutics, Inc, PharmaMar, Regeneron, Sattucklabs, Seagen, Sutro Biopharma, Exelisis; 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. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Immunogen, Mersana, MSD, Roche, AstraZeneca, GSK, Oncxerna, Shattuck Labs, Novartis, Epsilogen, Seagen, Eisai, Regeneron, Verastem; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview, Novacure; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Non-Financial Interests, Personal, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Personal, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, Academic sponsored trial PI (MONITOR-UK): GSK; Non-Financial Interests, Personal, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Personal, Leadership Role, Board Member: International Cancer Foundation (ICF). A. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, CLOVIS, GSK, Genmab, Alkermes, SUTRO, Roche, SOTIO, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics, Eisai, Immunogen, Regeneron, HederaDx, Illumina, Tubulis; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, CLOVIS, Roche, NOVOCURE, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB-500 phase III trial: ARAVIVE. K.H. Jung: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BIXINK, Celgene, Daiichi Sankyo, Eisai, Everest Medicine, Gilead Science, MSD, Novartis, Pfizer, Roche, Takeda. I. Lugowska: Financial Interests, Personal, Writing Engagement: Roche, ESMO; Financial Interests, Institutional, Other, Research grants: Roche; Financial Interests, Institutional, Other, Research grant: Agenus; Financial Interests, Personal and Institutional, Coordinating PI: MSD, Roche, BMS, Janssen, ASTRA, Amgen, RyVu, Incyte, Siropa, Mennarini,CELON, Pfizer, Agenus, Rhizen; Non-Financial Interests, Personal, Project Lead: MSCI; Non-Financial Interests, Personal, Other, Board Member: OECI; Other, Personal, Other, Robert Lugowski (my husband) co-ownership: Clininote. A. Manzano: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, Leo Pharma, Sanofi, Pharmamar, MSD; Financial Interests, Personal, Other, Support for attending meetings and/or travel: GSK, MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer, GSK, Pharmamar. B. Melichar: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Novartis, Merck Serono, E. Lilly, Pfizer, AstraZeneca. S. Siena: Financial Interests, Personal, Advisory Board, Advisory Board Member: Agenus, AstraZeneca, BMS, Checkmab, Daiichi Sankyo, GSK, Novartis, Seagen, T-One-Therapeutics. A. Fielding: Financial Interests, Personal, Full or part-time Employment, Employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Y. Ma: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S.D. Puvvada: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; 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. All other authors have declared no conflicts of interest.