Dato-DXd is an ADC comprising a humanized anti-TROP2 IgG1 mAb conjugated to a potent topoisomerase I inhibitor payload (DXd) via a stable tetrapeptide-based cleavable linker. Results from the ongoing phase I TROPION-PanTumor01 (NCT03401385) study showed encouraging antitumor activity of Dato-DXd in heavily pretreated patients (pts) with metastatic (m) NSCLC. Reported here are preliminary results in mTNBC; recruitment is ongoing.
TROPION-PanTumor01 is a 2-part study evaluating Dato-DXd IV Q3W in previously treated pts with solid tumors. Based on the dose-escalation phase limited to NSCLC pts, this expansion phase evaluated 6 mg/kg in pts with mTNBC that relapsed/progressed with standard treatment (TX). The primary endpoint was safety/tolerability. Secondary endpoints included efficacy assessed by ORR per RECIST v1.1 by blinded independent central review (BICR).
As of the Jan 8, 2021, data cutoff, 24 pts had ≥1 dose (6 mg/kg, n=22; 8 mg/kg, n=2 [treated prior to 6-mg/kg dose selection]), with 18 (75%) still on TX and 6 (25%) discontinued for PD. Median age was 57 y (range, 32-82 y); 71% had ≥3 prior lines of therapy. Prior therapies were taxanes (83%), platinum-based TX (50%), immunotherapy (33%), and sacituzumab govitecan (8%). Among 21 pts (6 mg/kg, n=19; 8 mg/kg, n=2) evaluable for response (≥1 postbaseline tumor assessment or discontinued TX), ORR by BICR was 43% (9 PRs), with 5 confirmed and 4 pending confirmation. The disease control rate was 95% (20/21 pts). Dose reductions due to AEs occurred in 6 pts (25%); no pts discontinued TX due to AEs. Any grade (Gr) and Gr ≥3 TEAEs regardless of causality occurred in 100% and 33% of pts, respectively. Most common TEAEs (any Gr [≥40%], Gr ≥3) were nausea (63%, 0%), stomatitis (63%, 13%), fatigue (42%, 4%), and vomiting (42%, 0%). No Gr ≥3 TEAEs of diarrhea or decreased neutrophil count/neutropenia were reported. No cases of TX-related ILD (adjudicated) were observed.
Preliminary results show that Dato-DXd had highly encouraging antitumor activity and a manageable safety profile in pts with refractory mTNBC; further confirmatory studies are warranted.
TROPION-PanTumor01 (NCT03401385) study.
Medical editorial assistance was provided by Allison Lytle, PhD, from ArticulateScience LLC, which was funded by Daiichi Sankyo, Inc.
Daiichi Sankyo Co, Ltd.
Daiichi Sankyo Co, Ltd.
A. Bardia: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Radius Health; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics ; Advisory/Consultancy, Research grant/Funding (institution): Biotheranostics Inc.; Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho; Advisory/Consultancy: Daiichi Sankyo/AstraZeneca; Advisory/Consultancy: Puma; Advisory/Consultancy, Travel/Accommodation/Expenses: Phillips; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Foundation Medicine. D. Juric: Advisory/Consultancy: Novartis, EMD Serono, Eisai, Genentech, Ipsen, Syros Pharmaceuticals, MapKure, Vibliome Therapeutics, Petra Pharma; Research grant/Funding (institution): Novartis, Genentech, Eisai, EMD Serono, Placon, Amgen, Syros Pharmaceuticals, InventisBio, Infinity Pharmaceuticals, Takeda, Pfizer. T. Shimizu: Advisory/Consultancy: Daiichi-Sankyo, AbbVie, Takeda Oncology, The Consortium on Harmonization of Institutional Requirements for Clinical Research (CHAIR) Joint Scientific Committee Review Member and External IRB Member of Phase 1 Trials in Hong Kong, HKSAR, China; Research grant/Funding (self): Novartis, AbbVie, Daiichi-Sankyo, Takeda Oncology, Eli Lilly, Loxo Oncology, Bristol-Myers Squibb, Eisai, Pfizer, AstraZeneca, Incyte, Symbio Pharmaceuticals, Chordia Therapeutics, 3D-Medicine, Five Prime, PharmaMar, Astellas . A. Tolcher: Leadership role: NEXT Oncology; Advisory/Consultancy: SOTIO Biotechnology; Advisory/Consultancy: Axlmmune; Advisory/Consultancy: Bayer; Advisory/Consultancy: Immunomet Therapeutics, Inc.; Advisory/Consultancy: Menarini; Advisory/Consultancy: Mersana; Research grant/Funding (institution): Naivre Pharma, Inc.; Research grant/Funding (institution): 3's Biotherapeutics; Research grant/Funding (institution): PMV Pharmaceuticals; Research grant/Funding (institution): Apros Therapeutics Inc.; Research grant/Funding (institution): Codiak Biosciences; Research grant/Funding (institution): Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Immunogen. A. Spira: Advisory/Consultancy: Amgen, Incyte, Mirati Therapeutics, Novartis; Shareholder/Stockholder/Stock options: Eli Lilly; Honoraria (self): Amgen, AstraZeneca/MedImmune, Bristol-Myers-Squibb, CytomX Therapeutics, Janssen Oncology, Merck, Novartis, Takeda; Research grant/Funding (self): Daiichi Sankyo. T. Mukohara: Research grant/Funding (self): Daiichi Sankyo, Inc., Sysmex, MSD, Pfizer, Sanofi, Seagen, AstraZeneca; Honoraria (self): Eisai, Pfizer, Novartis, Chugai, Eli Lilly, AstraZeneca. A.E. Lisberg: Spouse/Financial dependant, Employment, Stock: Boston Scientific; Honoraria (self): AstraZeneca, Bristol-Myers-Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys; Advisory/Consultancy: AstraZeneca, Bristol-Myers-Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys; Research grant/Funding (institution): Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL. I. Krop: Honoraria (self): Daiichi Sankyo, Inc., Macrogenics, Novartis, Merck, Context Therapeutics, Taiho Oncology, Genentech/Roche, Seattle Genetics; Research grant/Funding (self): Genentech/Roche, Pfizer. K.P. Papadopoulos: Advisory/Consultancy: Bayer, ArQule, Basilea; Research grant/Funding (institution): AbbVie, MedImmune, Daiichi Sankyo, Regeneron, Sanofi, ARMO BioSciences, ArQule, Amgen, Calithera Biosciences, Incyte, Merck, Peloton Therapeutics, ADC Therapeutics, 3D Medicines, EMD Serono, Syros Pharmaceuticals, Mersana, OncoMed, MabSpace Biosciences, J. E. Hamilton: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Travel/Accommodation/Expenses: Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Mersana; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millennium, Taplmmune Inc., Medivation, Tesaro, H3 Biomedicine, Radius Health, Acerta Pharma, Takeda, Macrogenics, AbbVie, Immunomedics, F; Advisory/Consultancy: Astra Zeneca, Novartis, Silverback Therapeutics, Black Diamond Therapeutics, CytomX Therapeutics, Dantari, H3 Biomedicine, Merck, Novartis, Seattle Genetics, Eisai. S. Damodaran: Advisory/Consultancy: Tempus, Taiho Pharmaceutical, Pfizer; Travel/Accommodation/Expenses: Phillips Gilmore Oncology Communications; Honoraria (self): Novartis; Research grant/Funding (institution): EMD Serono, Guardant Health, Taiho Pharmaceutical, Novartis. J. Greenberg, W. Gu, F.M. Guevara, T. Jikoh: Full/Part-time employment: Daiichi Sankyo, Inc.; Shareholder/Stockholder/Stock options: Daiichi Sankyo, Inc. F. Kobayashi, Y. Kawasaki: Full/Part-time employment: Daiichi Sankyo, Inc. F. Meric-Bernstam: Full/Part-time employment: MD Anderson Cancer Center; Advisory/Consultancy: Inflection Biosciences; Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Research grant/Funding (institution): eFFECTOR Therapeutics; Travel/Accommodation/Expenses: Beth Israel Deaconess Medical Center; Honoraria (self): Mayo Clinic; Honoraria (self): Rutgers Cancer Institute of New Jersey; Research grant/Funding (institution): Novartis, AstraZeneca, Calithera Biosciences, Bayer, Aileron Therapeutics, Puma Biotechnology, CytomX Therapeutics, Jounce Therapeutics, Zymeworks, Curis, Pfizer, AbbVie; Guardant H; Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): Debiopharm Group; Advisory/Consultancy: Samsumg Bioepis; Advisory/Consultancy: Spectrum Pharmaceuticals; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy: Origimed; Advisory/Consultancy: Xencor; Advisory/Consultancy: Mersana; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Silverback Therapeutics; Advisory/Consultancy: Immunomedics.