Abstract 1654P
Background
Oncogenic RET alterations are targetable markers in pts with TC. In the phase I/II ARROW trial (NCT03037385; data cutoff 12 Apr 2021; intention-to-treat [ITT] population), pralsetinib at 400 mg once daily (QD) induced overall response rates (ORR) of 51% in pts with RET-mutant medullary TC (RETm MTC) previously treated with cabozantinib and/or vandetanib (C/V), 72% in treatment-naïve pts with RETm MTC, and 86% in pts with previously treated RET fusion-positive TC (RET-fp TC). We report updated data with longer follow-up.
Methods
Adult pts with advanced or metastatic RET-altered TC from ARROW who initiated pralsetinib at 400 mg QD were included. Phase II primary endpoints: ORR by blinded independent central review (RECIST v1.1); safety. Key secondary endpoints: duration of response (DoR); progression-free survival (PFS); overall survival (OS). Efficacy endpoints were assessed in the ITT population (enrolment cutoff 18 Feb 2021); safety was assessed in all pts with RET-altered TC who initiated pralsetinib at 400 mg QD.
Results
At data cutoff (18 Oct 2021), the ITT population included 145 pts with RETm MTC (prior C/V: n=67; other prior systemic therapy: n=11; treatment naïve: n=67), and 25 pts with previously treated RET-fp TC. Pts with RETm MTC previously treated with C/V had an ORR of 52% (35/67; 95% CI 39.7–64.6; 2 complete responses [CR]; 33 partial responses [PR]), a median DoR of 25.8 months (95% CI 18.0–not estimable [NE]) and a median PFS of 25.8 months (95% CI 19.7–35.0). Treatment-naïve pts with RETm MTC had an ORR of 72% (48/67; 95% CI 59.3–82.0; 4 CR; 44 PR); median DoR and median PFS were not reached (NR). Pts with previously treated RET-fp TC had an ORR of 84% (21/25; 95% CI 63.9–95.5; 4 CR; 17 PR); median DoR was 23.6 months (95% CI 15.1–NE) and median PFS 25.4 months (95% CI 17.0–NE). In these three cohorts, median OS was NR. In the safety population (N=175), 29 pts (17%) experienced serious treatment-related adverse events (TRAE). One (0.6%) TRAE-related death (pneumocystis jirovecii pneumonia) was reported. TRAEs led to discontinuation or dose reduction in 6% and 53% of pts, respectively.
Conclusions
In this updated analysis (ITT population), pralsetinib continued to show efficacy and an acceptable safety profile in pts with RET-altered TC.
Clinical trial identification
NCT03037385.
Editorial acknowledgement
Further statistical support was provided by Hui Zhang of Blueprint Medicines Corporation. Third party medical writing assistance, under the direction of the authors, was provided by Tahmina Alam, MA, of Ashfield MedComms.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
M.I. Hu: Non-Financial Interests, Advisory Board, Steering committee for clinical trial (no financial reimbursement): Eli Lilly & Co; Financial Interests, Institutional, Principal Investigator, Research support to the institution: Eli Lilly & Co; Other, Co-investigator in a study: Eli Lilly & Co, Roche. V. Subbiah: Financial Interests, Personal, Advisory Board, One time advisory board: Incyte, Novartis, Eli Lilly/ Loxo Oncology; Financial Interests, Personal, Advisory Board, One time ad board: Roche, Pfizer; Financial Interests, Personal, Advisory Board, Ad hoc advisory board: Relay Therapeutics; Financial Interests, Institutional, Invited Speaker, Research funding to conduct Clinical trial: Eli Lilly/Loxo Oncology, Blueprint medicines, Novartis, Boston Pharmaceuticals, Pfizer, Turning Point Therapeutics, Amgen, Bayer, Roche/ Genentech, Exelixis, Berg Pharma, N W Biotherapeutics, Relay Therapeutics, AbbVie, Agensys, Inhibrx, Dragonfly therapeutics, Takeda; Other, I am employed at the University of Texas MD Anderson Cancer Center: The University of Texas MD Anderson Cancer Center; Other, I receive research funding from NCI: National Cancer Institute, USA. A.S. Mansfield: Financial Interests, Institutional, Advisory Board: AbbVie, BeiGene, BMS, Genentech, Janssen; Financial Interests, Research Grant, Grant number R21CA251923: NCI; Non-Financial Interests, Leadership Role, Non-remunerated member of the Board of Directors: Mesothelioma Applied Research Foundation; Financial Interests, Other, Travel support: Shanghai Roche Pharmaceuticals; Financial Interests, Research Grant, Grant number W81XWH-22-1-0021: Department of Defense; Financial Interests, Research Grant, ASPIRE award: Mark Foundation. M. Taylor: Financial Interests, Speaker’s Bureau: BMS, Eisai Inc, Merck, Blueprint Medicines; Financial Interests, Advisory Board: Bristol Myers Squibb, Eisai Inc, Novartis, Merck, Pfizer, Bayer, Sanofi/Genzyme, Regeneron, Loxo Oncology, Blueprint Medicines, Immuneonc, Exelixis, Cascade Prodrug. M.H.H. Schuler: Financial Interests, Other, Consultant(compensated): Amgen, AstraZeneca, BIOCAD, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda; Financial Interests, Invited Speaker: Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis; Financial Interests, Funding, Research funding to institution: AstraZeneca, Bristol Myers-Squib. V. Zhu: Financial Interests, Invited Speaker: AstraZeneca, Blueprint, Roche-Foundation Medicine, Roche/Genentech, Takeda; Financial Interests, Speaker’s Bureau: AstraZeneca, Blueprint, Roche/Genentech, Takeda; Financial Interests, Full or part-time Employment: Nuvalent; Financial Interests, Stocks/Shares, TP therapeutics: stock ownership until May 2020: Nuvalent, TP Therapeutics; Financial Interests, Advisory Role: AstraZeneca, BeiGene, Roche/Genentech, Takeda, TP Therapeutics, Xcovery. J. Hadoux: Financial Interests, Advisory Board: Ipsen, AAA, Roche, PharmaMar, Lilly; Financial Interests, Research Grant: Novartis. G. Curigliano: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celcuity, Daiichi Sankyo, Ellipsis, Exact Science, Exact Science, Lilly, Merck, Pfizer, Roche, Veracyte; Financial Interests, Personal, Writing Engagements: Pfizer; Financial Interests, Institutional, Funding, Phase I studies: Astellas, AstraZeneca, Blueprint Medicine, BMS, Daiichi Sankyo, Kymab, Novartis, Philogen, Roche, Sanofi; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Other, Coordinating PI - Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Advisory Role, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient Advocacy Association: Europa Donna; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Member of the Board of Directors, This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. L.J. Wirth: Financial Interests, Other, Consulting: Bayer, Coherus, Eisai, Merck, Morphic Therapeutic; Financial Interests, Other, Steering committee: Exelixis, Eli Lilly; Financial Interests, Other, DSMC committee: PDS Biotechnology. E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F.Hoffmann/La Roche, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol-Mayers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. D.R. Adkins: Financial Interests, Personal, Advisory Board: Merck, Cue Biopharma, Bluprint Medicine, Exelixis, Kura, Twoxar, Vaccinex, Xilio, Targimmune, Oncolys, Immunonitas; Financial Interests, Institutional, Invited Speaker: ISA, Pfizer, Eli Lilly, Merck, Celgene/BMS, Novartis, AstraZeneca, Atara Bio, Blueprint Medicine, Celldex, Aduro, Kura, Exelixis, Innate, Sensei, Matrix BIomed, Cue biopharma, Debiopharm, Epizyme, Hookipa, Shanghai De Novo, Roche; Financial Interests, Institutional, Funding, Was PI but now sub-investigator: Enzychem; Financial Interests, Institutional, Research Grant: CoFactor. M. Ahn: Financial Interests, Invited Speaker: AstraZeneca, AstraZeneca, Lilly, MSD, Daiichi Sankyo, Amgen, Merck, Takeda, Roche, Pfizer, Yuhan; Financial Interests, Advisory Board: AstraZeneca, Lilly, MSD, Daiichi Sankyo, Amgen, Merck, Takeda, Roche, Pfizer, Yuhan, Alphapharmaceuticals, Arcus. P.A. Cassier: Financial Interests, Personal, Advisory Board: Merck Serono/EMD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Advisor: OSE immunotherapeutics; Financial Interests, Institutional, Invited Speaker: AbbVie, Amgen, Blueprint, Exelixis, GSK, Janssen, Novartis, Roche, Taiho, LOXO/Eli Lilly; Non-Financial Interests, Institutional, Product Samples: plexxikon, Novartis, MSD, AstraZeneca, GSK. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Invited Speaker: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, Kanaph Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Other, Founder: DAAN Biotherapeutics. 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; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche. T. Barata: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. A. Zalutskaya: Financial Interests, Full or part-time Employment: Blueprint Medicines; Financial Interests, Stocks/Shares: Blueprint Medicines. A. Scalori: Financial Interests, Personal, Full or part-time Employment: Roche Products Ltd; Financial Interests, Personal, Stocks/Shares: Roche. M.S. Brose: Financial Interests, Advisory Board: Blueprint Pharma, Eisai, Loxo, Lilly, Bayer; Financial Interests, Institutional, Research Grant: Blueprint, Eisai, Loxo, Lilly, Bayer; Non-Financial Interests, Principal Investigator: Exelixis. All other authors have declared no conflicts of interest.