Tarloxotinib is a hypoxia-activated prodrug of a pan-ErbB kinase inhibitor that releases a potent irreversible active metabolite (tarloxotinib-E) under hypoxic conditions to preferentially deliver the active moiety to tumor versus normal tissues. Tarloxotinib has shown preclinical efficacy in
Patients (pts) with advanced NSCLC harboring an
As of June 12, 2020, 23 pts (11 cohort A, 11 cohort B, 1 cohort C) were treated with tarloxotinib. The disease control rate for all evaluable pts was 60% (12/20). In cohort A, the best response was stable disease (SD) in 6/11 (55%) and progressive disease (PD) in 5/11 (45%). In cohort B, 4/9 evaluable pts (44%) exhibited tumor reduction by RECIST and 2/9 pts experienced confirmed PR (22%), 4/9 (44%) pts had SD, and 3/9 (33%) pts had PD. Three pts in cohort B were treated beyond 6 months with 3 pts still ongoing. Most treatment emergent adverse events (TEAEs) were grade 1/2. Those occurring at >20% were prolonged QTc (60.9%), rash (43.5%), nausea (21.7%), and diarrhea (21.7%). The grade 3 TEAEs were prolonged QTc (34.8%), rash (4.3%), diarrhea (4.3%) and increased ALT (4.3%). Five of 23 (21.7%) pts required dose reduction and only 1/23 (4.3%) pts discontinued tarloxotinib due to a drug-related adverse event (infusion reaction).
Tarloxotinib exhibits antitumor activity in NSCLC pts with
NCT03805841.
Rain Therapeutics.
Rain Therapeutics.
S.V. Liu: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Boehringer Ingehleim; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Catalyst; Advisory/Consultancy: Celgene; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Inivata; Advisory/Consultancy: Janssen; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck/MSD; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Takeda; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Molecular Partners; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): RAPT; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): Turning Point Therapeutics. L.C. Villaruz: Advisory/Consultancy: Achilles; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): GSK. V.H.F. Lee: Honoraria (self): AstraZeneca; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): BMS; Research grant/Funding (self): Merck Sharp & Dohme; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Novartis. V.W. Zhu: Honoraria (self): AstraZeneca; Honoraria (self): Roche-Foundation Medicine; Honoraria (self): Roche / Genentech; Honoraria (self): Takeda; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche / Genentech; Advisory/Consultancy: Takeda; Advisory/Consultancy: TP Therapeutics; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche-Foundation Medicine; Speaker Bureau/Expert testimony: Roche / Genentech; Speaker Bureau/Expert testimony: Takeda; Shareholder/Stockholder/Stock options: TP Therapeutics. C.S. Baik: Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Calgene Inc.; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): SWOG; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): BluePrint Medicines; Research grant/Funding (institution): Daiichi Sankyo Inc; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): TP Therapeutics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly Oncology. A. Sacher: Honoraria (self): AstraZeneca; Honoraria (self): Merck; Honoraria (self): Genentech-Roche; Honoraria (self): Kisoli; Honoraria (self): BMS; Honoraria (self): Bayer; Honoraria (self): Tesaro; Honoraria (self): Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Genentech-Roche; Advisory/Consultancy: Kisoli; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer. C.E. McCoach: Honoraria (self): Novartis; Honoraria (self): Guardant health; Advisory/Consultancy: Genentech; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Revolution Medicines; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Takeda. D. Nguyen: Full/Part-time employment: Pacific Shores Medical Group. J.Y-C. Li: Advisory/Consultancy: Roche Hong Kong; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Lilly Oncology; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; Research grant/Funding (self): Roche Hong Kong; Travel/Accommodation/Expenses: Roche Hng Kong; Travel/Accommodation/Expenses: Taiho; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Sanomic & xcelom; Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Mundipharma. J.M. Pacheco: Honoraria (self): Takeda; Honoraria (self): Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Gerson Lehrman Group; Advisory/Consultancy: Hengrui Pharmaceuticals; Advisory/Consultancy: Jazz Pharmaceuticals; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda; Research grant/Funding (institution): Pfizer; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Takeda. C. Kim: Advisory/Consultancy: Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Altor Bioscience. T.F. Burns: Advisory/Consultancy: Novartis; Advisory/Consultancy: Blueprint Medicine; Advisory/Consultancy: Thermo Fisher Scientific. E.L. Schenk: Honoraria (self): Medscape; Honoraria (self): Physician’s Education Resource; Advisory/Consultancy: AbbVie; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Roche; Full/Part-time employment: Practice Update. N. Leighl: Honoraria (self): MSD; Honoraria (self): BMS; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Array; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): MSD. L. Tozzi: Shareholder/Stockholder/Stock options: Rain Therapeutics; Full/Part-time employment: Rain Therapeutics. D.R. Camidge: Advisory/Consultancy: Anchiarno; Advisory/Consultancy: Amgen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: CBT Pharmaceuticals; Advisory/Consultancy: Achilles; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bio-Thera; Advisory/Consultancy: Blueprint; Advisory/Consultancy: BeyondSpring; Advisory/Consultancy: Apollomics; Advisory/Consultancy: 14ner/Elevation; Advisory/Consultancy: Archer; Advisory/Consultancy: Helssin; Advisory/Consultancy: BMS; Advisory/Consultancy: Lilly; Advisory/Consultancy: Medtronic; Advisory/Consultancy: Ribon; Leadership role: AbbVie; Leadership role: AstraZeneca; Leadership role: BMS; Leadership role: GSK; Leadership role: Hanosh; Leadership role: Inhibrx; Leadership role: Lycera.