714MO - Datopotamab deruxtecan (Dato-DXd) in patients with endometrial (EC) or ovarian cancer (OC): Results from the phase II TROPION-PanTumor03 study

Background

The Phase 2, multicentre, open-label TROPION-PanTumor03 study (NCT05489211) comprises independent cohorts evaluating the TROP2-directed antibody-drug conjugate Dato-DXd as monotherapy and in combination in several tumour types. We present results from patients (pts) who received Dato-DXd monotherapy in the EC and OC cohorts.

Methods

The EC cohort enrolled pts with histologically documented recurrent unresectable advanced/metastatic endometrial carcinoma, whose disease had progressed on ≥1 line of platinum-based chemotherapy (CT). The OC cohort enrolled pts with histologically documented recurrent unresectable advanced/metastatic high-grade ovarian, fallopian tube, or primary peritoneal carcinoma whose disease had progressed after ≥1 line of platinum-based CT. Patients with platinum-sensitive and platinum-resistant OC were included. Both cohorts had ECOG PS of 0 or 1 and were unselected for TROP2 expression. The Dato-DXd monotherapy regimen is 6 mg/kg IV Q3W for both cohorts. Primary endpoints are objective response rate (ORR) and safety/tolerability.

Results

At data cut-off (March 1, 2024), 40 pts with EC and 35 pts with OC had received Dato-DXd. In the EC cohort, (median of 1 prior line of therapy; range 1–2) confirmed ORR was 27.5% (1 complete response [CR], 10 partial responses [PR]) and disease control rate (DCR) was 85.0%. Duration of response (DoR) was not yet reached. Median progression-free survival (PFS) was 6.3 months (95% CI 2.8–not yet reached). In the OC cohort (median of 2 prior lines of therapy; range 1–4), confirmed ORR was 42.9% (1 CR, 14 PR). DCR was 91.4%, DoR was 5.6 months and median PFS was 5.8 months (95% CI 4.1–7.1). Efficacy by subgroups will be presented. Safety is summarised in the table.

Table: 714MO

Conclusions

Dato-DXd monotherapy demonstrated encouraging efficacy and a manageable safety profile in pts with recurrent endometrial or ovarian cancer.

Clinical trial identification

NCT05489211. Release date: 5 August 2022.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Ella Spencer of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca in collaboration with Daiichi Sankyo.

Funding

AstraZeneca in collaboration with Daiichi Sankyo.

Disclosure

A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Inc., Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe Ltd, EMD Serono, Inc., F. Hoffmann-La Roche, GSK, GOG, ImmunoGen, Medison Pharma, Merck Sharp & Dohme de España, Mersana Therapeutics, Nov; Financial Interests, Personal, Other, Support for travel/accommodation: Roche, AstraZeneca, PharmaMar, GSK, Clovis. J.E. Ang: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, GSK; Non-Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, GSK, MSD, Pfizer. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daichii Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clincal trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Zymeworks; Financial Interests, Institutional, Local PI, drug supply for clinical trial: BeiGene; Financial Interests, Local PI: Roche. K. Yonemori: Financial Interests, Personal, Invited Speaker, Lecture fees: Eisai, Pfizer, Eli Lilly, Takeda, Chugai, MSD, FujiFilm Pharma, Bayer, Boehringer Ingelheim, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis, Eisai, Chugai, AstraZeneca, Takeda, Genmab, Sanofi, OncXerna; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. R. Kristeleit: Financial Interests, Personal, Other, Personal fees: GSK. C. Lin: Financial Interests, Personal, Other, Travel support: BeiGene, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AbbVie, PharmaEngine, Merck KGaA, Boehringer Ingelheim, Anbogen, IMPACT Therapeutics; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche; Financial Interests, Personal, Other, Travel Support: IMPACT Therapeutics; Financial Interests, Institutional, Other, Local principal investigator: Nuvalent. T. Satoh: Financial Interests, Personal, Invited Speaker, invited speaker and advisory: Ono Pharmaceutical, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Invited speaker and advisory: Bristol Myers; Financial Interests, Personal, Invited Speaker, Invited speaker and advisory: Elli-Lilly, Yakult-Honsha; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Merck-Biopharm, Takeda, Taiho; Financial Interests, Personal, Advisory Board: Takara-Bio; Financial Interests, Institutional, Local PI, Research Grant: Merck-Biopharm, Ono Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, Bristol Myers, Eli-Lilly, Daiichi Sankyo, Parexell, Taiho, Amgen, Pfizer. P. Estevez Garcia: Financial Interests, Personal, Advisory Board: PharmaMar, Clovis, GSK, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, GSK, AstraZeneca, Eisai, PharmaMar; Financial Interests, Institutional, Research Grant: GSK. M.A.N. Sendur: Financial Interests, Personal, Invited Speaker: Astellas, Roche, MSD, Pfizer, Novartis, Janssen; Financial Interests, Personal, Advisory Board: Astellas, Roche, MSD, Pfizer, Novartis, Janssen. L. Medina Rodríguez: Financial Interests, Personal, Invited Speaker: Novartis, Servier; Financial Interests, Personal, Other, Travel: Merck. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. I. Lugowska: Financial Interests, Personal, Other, Personal fees for writing engagements: ESMO, Roche; Financial Interests, Personal and Institutional, Principal Investigator, Personal and institutional fees as coordinating principal investigator (PI): Agenus, Amgen, AstraZeneca, Bristol Myers Squibb, Celon, Incyte, Janssen, Menarini, MSD, Pfizer, Rhizen, Roche, RyVu and Siropa; Financial Interests, Institutional, Research Grant, Institutional research grants: Agenus, Roche; Non-Financial Interests, Personal, Other, Non-financial interests as project lead for MSCI and board member for OECI; Financial Interests, Personal, Ownership Interest, Spouse has co-ownership of: Clininote. I.L. Ray-Coquard: Financial Interests, Personal, Other, Honoraria: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Serono, Novartis, Amgen, Tesaro, Clovis, GSK, MSD, Roche, BMS; Financial Interests, Personal, Advisory Role, Advisory/consulting fees: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Serono, Novartis, Amgen, Tesaro, Clovis; Financial Interests, Personal, Research Grant, Research grant/funding (self): MSD, Roche, BMS; Financial Interests, Institutional, Research Grant, Research grant/funding (institution): MSD, Roche, BMS, Novartis, AstraZeneca, Merck Serono; Financial Interests, Personal, Other, Travel support: Roche, AstraZeneca, GSK. A.M. Oza: Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca. J.L. Zhao, S. Gajavelli, J. Filant, S. Bodla: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Y.Y. Janjigian: Financial Interests, Personal, Advisory Board: AbbVie, Arcus Biosciences, Ask- Gene Pharma, Inc., AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Inc., Eli Lilly, GSK, Guardant Health, Inc., Imugene, Lynx Health, Merck, Sanofi Genzyme, Seagen, Zymeworks Inc.; Financial Interests, Personal, Other, Consulting: Amerisource Bergen, Astellas, Basilea Pharmaceutica, Geneos Therapeutics, Imedex, Inspirna, Mersana Therapeutics, Paradigm Medical Communications, Pfizer, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting and Invited Speaker: Arcus Biosciences, AstraZeneca, Clinical Care Options, HMP Education, Merck Serono, PeerView Institue, Research to Practice; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ed MedResources (OncInfo), H.C. Wainwright & Co., LLC, Merck, TotalCME, Talem Health; Financial Interests, Personal, Other, Consulting, Invited Speaker and Chair of Giants of Cancer Care Steering Committee: Michael J. Hennessy Associates; Financial Interests, Personal, Other, Consulting and Moderator: Physicians' Education Resource, LLC; Financial Interests, Personal, Stocks/Shares, Stock option: Inspirna; Financial Interests, Personal and Institutional, Research Grant: NCI, Department of Defense, Cycle for Survival, Fred's Team, Inspirna, Bayer, Genetech/Roche, Bristol Myers Squibb, Eli Lilly, Merck, Transcenta, Stand Up To Cancer, AstraZeneca, Arcus Biosciences, Astellas; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Transcenta Holding Limited. F. Meric-Bernstam: Financial Interests, Personal, Advisory Role, Consulting: AbbVie, Aduro BioTech,Inc., Alkermes, AstraZeneca, Daiichi Sankyo Co. Ltd., DebioPharm, Ecor1 Capital, eFFECTOR Therapeutics, F. Hoffmann-La Roche Ltd., GT Apeiron, Genentech,Inc., Harbinger Health, IBM Watson, Infinity Pharmaceuticals, Jackson Laboratory; Financial Interests, Personal, Advisory Role, Advisory Committee: Black Diamond, Biovica, Eisai, FogPharma, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Sanofi, Silverback Therapeutics, Spectrum Pharmac; Financial Interests, Institutional, Research Grant, Sponsored Research (to the institution): Aileron Therapeutics, Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech,Inc., Guardant Health,Inc., Klus; Financial Interests, Personal, Other, Travel: European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO).