Abstract 1170P
Background
Pralsetinib is FDA/EMA approved for the treatment of advanced RET fusion+ NSCLC based on the global multicohort, open-label, Phase 1/2 ARROW study. Prior results from ARROW show that pralsetinib has promising anti-tumour activity with a manageable safety profile in advanced RET fusion+ NSCLC (Gainor JF, et al. Lancet Oncol 2021). We present updated data from the RET fusion+ NSCLC cohort after an additional 16 months of follow-up since the previous analysis.
Methods
Phase 1 established the recommended Phase 2 dose of pralsetinib (400mg once daily). In the RET fusion+ NSCLC cohort, pts ≥18 years with ECOG PS 0–2 (limited to 0–1 after a protocol amendment) and locally documented RET fusions received pralsetinib until disease progression, intolerance or withdrawal. Primary endpoints in Phase 2 were overall response rate (ORR; blinded independent central review [BICR] per RECIST v1.1) and safety.
Results
At the updated data cut-off of 4 Mar 2022, 281 pts with RET fusion+ NSCLC had received pralsetinib 400mg, of whom 260 had measurable disease at baseline per BICR. The ORR was 63.1% in pts with prior platinum treatment and 77.6% in those who were systemic treatment-naïve (Table), consistent with earlier data cuts. Median overall survival was 44.3 months in pre-treated pts and not reached in treatment-naïve pts. In the safety population (n=281), median treatment duration was 15.0 months with a median relative dose intensity of 86.1%. The most common (≥10%) grade ≥3 adverse events (AEs) were anaemia (23.1%), hypertension (17.8%), decreased neutrophil count (14.2%), pneumonia (12.8%) and neutropenia (10.7%). Overall, 10% of pts discontinued pralsetinib due to treatment-related AEs. Table: 1170P
| Prior platinum treatment | No prior systemic treatment | |
| Measurable disease population (n=260) | n=130 | n=107 |
| ORR, n (%) [95% CI] | 82 (63.1) [54.2–71.4] | 83 (77.6) [68.5–85.1] |
| Median DOR, months (95% CI) Median follow-up, months | 38.8 (14.8–40.4) 29.3 | 13.4 (9.4–23.1) 20.2 |
| Efficacy population (n=281) | n=141 | n=116 |
| Median PFS, months (95% CI) Median follow-up, months | 16.4 (11.4–22.3) 28.1 | 12.6 (9.2–16.6) 21.3 |
| Median OS, months (95% CI) Median follow-up, months | 44.3 (26.9–44.3) 29.4 | NR (31.9–NR) 22.1 |
| CI, confidence interval; DOR, duration of response; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival |
Conclusions
With additional follow-up, pralsetinib demonstrated robust and durable clinical activity in pts with advanced RET fusion+ NSCLC, including systemic treatment-naïve pts. No new or unexpected safety findings emerged from this updated data cut.
Clinical trial identification
NCT03037385.
Editorial acknowledgement
Third-party medical writing assistance, under the direction of authors, was provided by Fiona Duthie, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals. F. Griesinger: Financial Interests, Personal, Invited Speaker: Astra, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Siemens, Tesaro/GSK, Amgen, Sanofi; Financial Interests, Personal, Writing Engagements: Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Astra, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Siemens, Tesaro/GSK, Amgen, Sanofi; Financial Interests, Institutional, Research Grant: Astra, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Siemens, Tesaro/GSK, Amgen, Sanofi; Financial Interests, Institutional, Funding: Astra, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Siemens, Tesaro/GSK, Amgen, Sanofi; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Novartis; Other, Personal, Member: ASCO, ASH, ESMO, DGHO, DKK, AIO. G. Curigliano: Financial Interests, Personal, Invited Speaker: MSD; Advisory Board: Mylan, Daichii Sankyo; Lilly, Pfizer, Merck, Foundation Medicine, Samsung, Celltrion, Novartis, Gliead; Other, Personal, Writing Engagements: Novartis, BMS; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Advisory Board: MSD, Mylan, Daichii Sankyo; AstraZeneca, Novartis, Lilly, Pfizer, Merck, Foundation Medicine, Samsung, Celltrion, Gilead; Other, Personal, Research Grant: Merck, AstraZeneca; Other, Personal, Principal Investigator: MSD, Mylan, Daichii Sankyo; AstraZeneca, Novartis, Lilly, Pfizer, Merck, Foundation Medicine, Samsung, Celltrion, Gliead; Other, Personal, Member: ESMO; ASCO; AIOM, AACR; Other, Personal, Advisory Role, Advisory role: Ellipsis. M. Thomas: Financial Interests, Personal, Advisory Board: AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda; Non-Financial Interests, Personal, Advisory Board, travel costs: AstraZeneca, Beigene, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda. V. Subbiah: Financial Interests, Personal, Advisory Board, One time advisory board: Incyte, Novartis, Eli Lilly/ Loxo Oncology, Roche, Relay Therapeutics, Pfizer; 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 Therapeut; Other, Employed at the University of Texas MD Anderson Cancer Center; Other, I receive research funding from National Cancer Institute, USA. C.S. Baik: Financial Interests, Personal, Advisory Board: AstraZeneca, Blueprint Medicines, Daiichi, Takeda, Turning Point Therapeutics, Guardant Health, Pfizer, Janssen, Regeneron, Silverback Therapeutics; Financial Interests, Institutional, Research Grant: Spectrum, Turning Point Therapeutics, Daiichi Sankyo, AbbVie, AstraZeneca, Lilly, Loxo, Jansen, Rain Therapeutics, Pfizer, Blueprint Medicines. D.S.W. Tan: Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer, GSK, Novartis; Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Lilly, Loxo Oncology, Merrimack, Novartis, Pfizer, Takeda; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim, Merck, Roche. D.H. Lee: Financial Interests, Personal, Advisory Board, Outside the submitted work: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, ChongKeunDang, Janssen, MSD, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube, AbbVie, Takeda. E. Garralda: Financial Interests, Personal, Speaker’s Bureau: Thermo Fisher, Bristol Myers Squibb, Roche/Genentech - F.Hoffmann/La Roche, Lilly, Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech - F.Hoffmann/La Roche, Ellipses Pharma, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, SeaGen, Alkermes, Thermo Fisher, Bristol-Mayers Squibb, MabDiscovery, Anaveon, F-Star Therapeutics, Hengrui, Lilly, Novartis; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho, BeiGene; Financial Interests, Institutional, Principal Investigator: Affimed Gmbh, Amgen SA, Anaveon AG, AstraZeneca AB, Biontech Gmbh, Catalym Gmbh, Cytomx, F.Hoffmann La Roche Ltd, F-Star Beta Limited, Genentech Inc., Genmab B.V., Hutchison Medipharma Limited, Icon, Imcheck Therapeutics, Immunocore Ltd. D. Kim: Financial Interests, Personal, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society, Asian Thoracic Oncology Research Group; Other, Personal, Writing Engagements, Medical writing assistance: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi Sankyo, GSK, Pfizer, MSD, Merck, Novartis, Roche, Takeda, Yuhan; Non-Financial Interests, Personal, Advisory Board, no payment: Amgen, AstraZeneca, BMS/Ono Pharmaceuticals, Daiichi Sankyo, GSK, Janssen, Merck, MSD, Pfizer, SK Biopharm, Takeda; Other, Personal, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology; Financial Interests, Institutional, Research Grant: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda; Other, Personal, Principal Investigator, coordinating PI: Chong Keun Dang; Financial Interests, Personal, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea; Other, Personal, Other, travel support: Amgen, Daiichi Sankyo, International Association for the Study of Lung Cancer, Asian Thoracic Oncology Research Group, Taiwan Lung Cancer Society. A.J. Van Der Wekken: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Pfizer; Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Takeda. J. Gainor: Financial Interests, Personal, Ownership Interest: Ironwood Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Ironwood Pharmaceuticals; Financial Interests, Personal, Research Grant: Adaptimmune, ALX Oncology, Ariad, Array BioPharma, AstraZeneca, Blueprint Medicines Corporation, BMS, Genentech, Jounce Therapeutics, Merck, Novartis, Tesaro; Financial Interests, Personal, Advisory Role: Agios, Amgen, Array BioPharma, Blueprint Medicines Corporation, BMS, Genentech, Gilead Sciences, Jounce Therapeutics, Lilly, Loxo Oncology, Merck, Mirati, Silverback Therapeutics, GlydeBio, Moderna Therapeutics, Oncorus, Regeneron, Takeda, Nuvalent, iTeo; Other, Personal, Other, Received honoraria: Ariad, Incyte, Merck, Novartis, Pfizer, Takeda; Other, Personal, Has an immediate family member who is an employee of Ironwood Pharmaceuticals. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker: Roche, MSD, BMS, AZ, Lilly, Pharmam, BeiGene, Daichii, Medscape, Per; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AZ, Merck Sharp & Dohme, BMS, Janssen-Cilag, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO, Small Lun; Financial Interests, Personal, Other, Foundat: AECC, ONCOSUR; Financial Interests, Personal, Other, President: ASEICA. S.V. Liu: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, Boehringer Ingelheim, Bristol Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Lilly, Merck/MSD, Novartis, Regeneron; Financial Interests, Institutional, Research Grant: Alkermes, Bayer, Blueprint, Bristol Myers Squibb, Elevation Oncology, Genentech, Gilead, Lilly, Merck, Merus, Nuvalent, Pfizer, Rain Therapeutics, RAPT, Turning Point Therapeutics. D.W. Bowles: Financial Interests, Personal, Advisory Board: Exelixis. A. Zalutskaya: Financial Interests, Personal, Full or part-time Employment: Blueprint Medicines Corporation; Financial Interests, Personal, Stocks/Shares: Blueprint Medicines Corporation. T. Ruf: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. A. Rahman: Financial Interests, , Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Stocks/Shares: Merck/MSD, F. Hoffmann-La Roche, Ltd. G. Chen: Financial Interests, , Full or part-time Employment: Genentech. J. Mazieres: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, MSD, Daiichi, Novartis, Amgen; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Lilly, Merck; Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Pierre Fabre, BMS; Non-Financial Interests, Personal, Principal Investigator: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Sanofi, Pfizer, Merck.