LBA34 - 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). 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). Table: LBA34

NR, not reached

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. (Funded by BioNTech; ClinicalTrials.gov number; NCT04503278).

Clinical trial identification

NCT04482309.

Editorial acknowledgement

Medical writing and editorial support was provided by Neil Patel, MSc, of Helios Medical Communications, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca and Daiichi Sankyo.

Funding

AstraZeneca and Daiichi Sankyo.

Disclosure

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, Travel support: European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO); Other, Travel Support: Cholangiocarcinoma Foundation. V. Makker: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Clasi, Duality, Eisai, Faeth, Karyopharm, Merck, Takeda, Zymeworks, Cullinan; Other, Support for attending meetings and/or travel: Merck, Eisai; Other, Unpaid Consultant: Clovis, Duality, Eisai, Faeth, GSK, Iteos, Karyopharm, Lilly Moreo, Morphosys, Novartis, Zymeworks, Merck, MSD, Immunocore, Regeneron, iTEOS, Sutro, Cullinan. A. Oaknin: Financial Interests, Institutional, Research Grant: AbbVie, Advaxis Inc, Aeterna Zentaris, Amgen, Aprea Therapeutics, Bristol Myers Squibb, Clovis Oncology Inc, Eisai, Immunogen Inc, Merck Sharps & Dohme de Espana, Millenium Pharmaceuticals Inc, PharmaMar, Regeneron Pharmaceuticals, Roche, Tesaro Inc; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: Agenus, AstraZeneca, Clovis Oncology, Corcept Theraupeutics, Deciphera Pharmaceuticals, Eisai Exelisis, EMD Serono, F.Hoffman-La Roche, Genmab, GSK, ImmunoGen, Itheos, Merck Sharps & Dohme de Espana, SA, Mersana Therapeutics, Novocure, OneXerna Therapeutics Inc, PharmaMar, Regeneron, Sattucklabs, Seagen, Sutro Biopharma; Financial Interests, Personal, Speaker, Consultant, Advisor: NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, ESO, AstraZeneca, GSK; Other, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, PharmaMar, Roche; Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, Exelisis, EMD Serono, F.Hoffman-La Roche, Genmab, GSK, ImmunoGen, Itheos, Merck Sharps & Dohme de Espana, SA, Mersana Therapeutics, Novocure, OneXerna Therapeutics Inc, PharmaMar, Regeneron, Sattucklabs, Seagen, Sutro Biopharma; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Gynecologic Cancer Intergroup, European Society for Medical Oncology; Other, Personal, Other: Gynecologic Cancer Intergroup, European Society for Medical Oncolog, American Society of Clinical Oncology, Spanish Society of Medical Oncology, Spanish Society of Medical Oncology, GOGFoundation. D. Oh: Financial Interests, Personal, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok; 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. S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Epsilogen, GSK, Immunogen, Merck Sharpe Dohme, Mersana, Novartis, Oncxerna, Seagen, Shattuck Labs, Regeneron, Verastem; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Clovis, GSK, Immunogen, Merck, Sharpe Dohme Mersana, Pfizer, Roche, Takeda, Novacure, Research to Practice, Medscape; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: International Cancer Foundation; Financial Interests, Personal, Stocks/Shares: PerciHealth; Other, Support for attending meetings and/or travel: Verastem, GSK. A. Gonzalez Martin: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; Other, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, GSK, MSD; Financial Interests, Personal, Advisory Board: Alkermes, AstraZeneca, Amgen, Clovis, Eisa, GSK, Immunogen, GenMab, Kartos, Sutro, Roche, Sotio, Macrogenics, Mersana, MSD, Pharmamar, Novartis, Oncoinvent, Regeneron, HederaDx, Illumina, Tubulis, Daiichi Sankyo; Other, Institutional, Other: GlazoSmithKline, Roche. K.H. Jung: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: AstraZeneca, Bixink, Celgene, Daiichi Sankyo, Eisai, Everest Medicine, Gilead Science, MSD, Novartis, Pfizer, Roche, Takeda Pharmaceuticals. I. Lugowska: Financial Interests, Institutional, Research Grant: Agenus, Roche; Other, Personal, Other: Roche, European Society of Medical Oncology, Morgan Stanley Capital International, Clininote; Other, Personal and Institutional, Other: Agenus, Bristol Myers Squibb, MSD, Roche, Janssen, AstraZeneca, Amgen, RyVu, Incyte, Siropa, Mennarini, Celon, Pfizer, Rhizen, Organisation of European Cancer Institutes (OECI). A. Manzano Fernández: Financial Interests, Research Grant: AstraZeneca; Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, GSK, Leo Pharma, Sanofi, Pharmamar, MSD; Other, Support for attending meetings and/or travel: GSK, MSD, AstraZeneca; Financial Interests, Advisory Board: Boehringer, GSK, PharmaMar. B. Melichar: Financial Interests, Speaker, Consultant, Advisor, Consulting fees: Roche, Pfizer, BMS, Novartis, MSD, Merck Serono, Servier, AstraZeneca, Amgen, Eli Lilly; Financial Interests, Speaker, Consultant, Advisor, Honoraria for speeches: Roche, Pfizer, BMS, Novartis, MSD, Merck Serono, Servier, AstraZeneca, Amgen, E. Lilly; Other, Support for attending meetings and/or travel: AstraZeneca, Merck; Financial Interests, Other, Support for attending meetings and/or travel: Serono, BMS, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck Serono, MSD, Novartis, Pfizer, Roche. S. Siena: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bristol Myers Squibb, ChecKMab, Daiichi Sankyo, GSK, MSD, Novartis, Seagen, T-One-Therapeutics. A. Fielding: Financial Interests, Personal, Stocks/Shares: AstraZeneca; Other, Personal, Other: AstraZeneca; Financial Interests, Other, Employee: AstraZeneca. Y. Ma: Financial Interests, Other, Employee: AstraZeneca; Financial Interests, Stocks/Shares, Ex Beigene employee and hold Beigene stock: Beigene. S.D. Puvvada: Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Other, Employee: AstraZeneca. J. Lee: Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Other, Personal, Other: AstraZeneca, Takeda, MSD, Roche, Eisai, AstraZeneca, ImmunoGen, MSD, OncoQuest, MSD, ONO, Takeda; Other, Institutional, Other: Alkermes, AstraZeneca, BeiGene, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon. All other authors have declared no conflicts of interest.