Background

Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-mutant MTC and RET fusion-positive thyroid and lung cancers.

Methods

Updated analysis of selpercatinib in pts with RET fusion-positive thyroid cancer (TC), in LIBRETTO-001 (NCT03157128) was conducted after additional follow up (f/u) of 19 months. Primary endpoint was objective response rate (ORR, RECIST 1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression free survival (PFS), and safety.

Results

Efficacy of selpercatinib after RAI (where RAI appropriate) was evaluated in systemic treatment-naïve pts (N=24) and pre-treated pts (N=41) (Table). Naïve and pre-treated pts achieved an ORR of 95.8% and 85.4%, respectively (Table). For pre-treated pts DoR was 26.7 months and PFS was 27.4 months. DoR and PFS data for treatment-naïve pts are still immature approaching and at 2 years, with response ongoing in most pts. At 2 yrs, 95.2% of naïve pts and 57.1% of pre-treated pts remained progression free. In the safety population (N=66), the most common ≥3 grade treatment-emergent adverse events (TEAEs) were: hypertension (15.2%), hyponatraemia (10.6%), diarrhea (7.6%), lymphopenia (7.6%) and increased alanine aminotransferase (6.1%). Two pts (3.0%) discontinued treatment due to TEAEs; 1 pt (1.5%) of these was considered related. Table: 2229P

NE; Not estimated.

Conclusions

With longer f/u and additional pts, selpercatinib continues to demonstrate very durable responses in pts with RET-fusion thyroid cancer with or without prior therapy, suggesting use of selpercatinib as first systemic therapy appears to be highly effective in treatment of TC. The safety remained tolerable despite longer duration on treatment.

Clinical trial identification

NCT03157128.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

L.J. Wirth: Financial Interests, Personal, Advisory Board: Bayer, Coherus, Eli Lilly, Eisai, Exelixis; Financial Interests, Personal, Other, Consultant: Curie Therapeutics, Morphic Therapeutics, Tome Biosciences; Financial Interests, Personal, Other, DMSC: PDS Biotherapeutics; Financial Interests, Institutional, Steering Committee Member: Novartis, Eli Lilly. P. Cassier: Financial Interests, Personal, Advisory Board: Merck Serono/EMD, Roche, Amgen, Boehringer ingelheim; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Advisor: OSE Immunotherapeutics; Financial Interests, Institutional, Local PI: AbbVie, Blueprint, Exelixis, GSK, Janssen, Novartis, Roche, Taiho, Loxo/Eli Lilly; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. V. Subbiah: Financial Interests, Institutional, Research Funding: Loxo/Eli Lilly. F.P. Worden: Financial Interests, Personal, Advisory Board: Regeneron, Coherus, Merck, EMD, Serono, Eisai, Eli Lilly, Soligenix, Exelixis; Financial Interests, Personal, Advisory Role: Eisai, EMD, Serono; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Research Funding: Kura Oncology, Merck, Regeneron, Adlai Nortye, Eli Lilly, Loxo. B.J. Solomon: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Merck, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Roche/Genentech; Financial Interests, Personal, Advisory Board: Amgen, Roche-Genentech, Eli Lilly, Takeda, Janssen; Financial Interests, Personal, Full or part-time Employment, Employed as a consultant Medical Oncologist at Peter MacCallum Cancer Centre: Peter MacCallum Cancer Centre; Financial Interests, Personal, Member of Board of Directors: Cancer Council of Victoria, Thoracic Oncology Group of Australasia; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Steering Committee Member, Principal Investigator and Steering Committee Chair: Roche/Genentech, Pfizer; Financial Interests, Institutional, Steering Committee Member: Novartis. J. Hadoux: Financial Interests, Personal, Advisory Board: Ipsen, Lilly, Pharma Mar; Financial Interests, Institutional, Invited Speaker: AAA, Pfizer; Financial Interests, Institutional, Advisory Board: Eisai, HRA pharma. D. Weiler: Financial Interests, Personal, Advisory Board, Invited Speaker: Lilly, Roche; Financial Interests, Personal, Advisory Board: MSD, Merck. P. Tomasini: Financial Interests, Personal, Expert Testimony: AZ, Roche, BMS, Takeda, Amgen, JNJ. B.D. Baier: Financial Interests, Personal, Expert Testimony: Eli Lilly. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. Y. Lin, T. Bayt: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks or ownership: Eli Lilly and Company. P. Maeda: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks or ownership: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Bayer. A. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem Oncology, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Amgen, Janssen, EcoR1, Monte Rosa; Financial Interests, Personal, Other, CME: Medscape, Onclive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options, AiCME; Financial Interests, Personal, Other, CME, Consulting: Axis; Financial Interests, Personal, Other, Consulting: Nuvalent, Merus, mBrace, EPG Health, Harborside Nexus, Ology, TouchIME, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Remedica Ltd, RV More; Financial Interests, Personal, Stocks/Shares: Treeline Biosciences; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, stocks: mBrace; Financial Interests, Institutional, Funding, Research Funding: Pfizer, Exelixis, GSK, Teva, Taiho, PharmaMar; Financial Interests, Personal, Funding, Research: Foundation Medicine; Non-Financial Interests, Member: ASCO, AACR, IASLC; Other, Food/Beverage: Merck, PUMA, Merus; Other: Boehringer Ingelheim. All other authors have declared no conflicts of interest.