Abstract 1656P
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. In the previous report, duration of response (DoR) and progression free survival (PFS) follow-up (f/u) was limited.
Methods
Updated analysis of selpercatinib in pts with RET-mutant MTC in LIBRETTO-001 (NCT03157128) was conducted after an additional f/u of 15 months. Primary endpoint was objective response rate (ORR, RECIST 1.1) by independent review committee (IRC). Secondary endpoints included DoR, PFS, and safety.
Results
Efficacy of selpercatinib was evaluated in cabozantinib/vandetanib (cab/van) naïve pts (N=142) and cab and/or van pre-treated pts (N=151) (Table). Naïve and pre-treated pts achieved an ORR of 81.0% and 73.5%, respectively. Despite a median f/u of ∼2 yrs, DoR and PFS data are still immature, with response ongoing in most pts. At 2 yrs, 81.1% of naïve pts and 64.4% of pre-treated pts remained progression free. In the safety population (MTC pts with ≥ 1 dose, N=319), the most common ≥3 grade treatment-emergent adverse events (TEAEs) were: hypertension (21.6%), increased aspartate (7.2%)/alanine (8.2%) aminotransferase, hyponatraemia (7.5%), lymphopenia (6.3%), and diarrhea (6.3%). In total, 23 pts (7.2%) discontinued treatment due to TEAEs, including 13 pts (4.1%) due to treatment related TEAEs. Table: 1656P
Efficacy of selpercatinib in RET-mutant MTC
| Cab/van naïve (N=142) | Prior cab and/or van (N=151) | |
| ORR by IRC, % (95% CI) | 81.0 (73.6-87.1) | 73.5 (65.7-80.4) |
| Complete response, n (%) | 22 (15.5) | 14 (9.3) |
| Partial response, n (%) | 93 (65.5) | 97 (64.2) |
| Stable Disease, n (%) | 22 (15.5) | 31 (20.5) |
| Progressive Disease, n (%) | 2 (1.4) | 2 (1.3) |
| Not Evaluable (NE), n (%) | 3 (2.1) | 7 (4.6) |
| PFS by IRC | ||
| Median PFS, months (95% CI) | NE (NE-NE) | 34 (25.7-NE) |
| Censored, % | 83.1 | 62.3 |
| PFS rate at 24 months, % (95% CI) | 81.1 (72.4-87.3) | 64.4 (55.4-72.0) |
| Median f/u, months | 24.5 | 27.6 |
| DoR by IRC | ||
| Median DoR, months (95% CI) | NE (NE-NE) | NE (27.2-NE) |
| Censored, % | 87.0 | 69.4 |
| DoR rate at 24 months, % (95% CI) | 83.7 (73.0-90.4) | 64.5 (52.9-73.9) |
| Median f/u, mo | 20.3 | 22.9 |
Conclusions
With longer f/u and additional pts, selpercatinib continues to demonstrate very durable responses in MTC patients with or without prior cab/van therapy, suggesting first line use of selpercatinib appears to be highly effective in treatment of MTC. The safety profile is unchanged despite longer duration on treatment. Disclosure: Funded by Eli Lilly and Company.
Clinical trial identification
NCT03157128.
Editorial acknowledgement
Shannon Nelson, an employee of Eli Lilly and Company, provided editorial and scientific writing support on the abstract.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
M. Kroiss: Financial Interests, Institutional, Funding: Eli Lilly and Company, Loxo Oncology; Financial Interests, Institutional, Advisory Role: Eisai, Bayer, Eli Lilly and Company; Financial Interests, Institutional, Invited Speaker: Eli Lilly and Company, Eli Lilly and Company. E.J. Sherman: Financial Interests, Institutional, Writing Engagements: Eli Lilly and Company; Financial Interests, Institutional, Funding: Eli Lilly and Company, Roche, Regeneron, Fore; Financial Interests, Personal, Advisory Role, Consulting fees: Regeneron, Exelixis, Eli Lilly and Company, Eisai, Merck; Financial Interests, Personal, Advisory Board, executive committee, Board of Directors: ITOG. L.J. Wirth: Financial Interests, Personal, Advisory Role, Consulting: Bayer, Coherus, Eisai, Merck, Morphic Therapeutic ; Financial Interests, Personal, Advisory Role, steering committee: Exelixis, Eli Lilly and Company; Financial Interests, Personal, Advisory Role, DSMC committee: PDS Biotechnology . M.E. Cabanillas: Financial Interests, Institutional, Research Grant: Genentech, Merck, Eisai; Financial Interests, Personal, Advisory Role, Consulting fees: Eli Lilly and Company; Financial Interests, Personal, Invited Speaker: Exelixis; Financial Interests, Personal, Advisory Role: Exelixis, Bayer. B. Robinson: Financial Interests, Personal, Invited Speaker: Eli Lilly and Company, Eisai; Financial Interests, Institutional, Funding: Eli Lilly and Company. 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.E. Drilon: Financial Interests, Personal, Advisory Board: : Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner/Elevation On; Financial Interests, Personal, Stocks/Shares: Treeline Bio; Financial Interests, Institutional, Research Grant: Pfizer Exelixis GlaxoSmithKlein Teva Taiho PharmaMar, Foundation Medicine; Financial Interests, Personal, Other, Copyright: Selpercatinib-Osimertinib (filed/pending) Loxo Oncology; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, Food/beverage: Merck, Puma, Merus, Boehringer Ingelheim ; Financial Interests, Personal, Other, CME: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, Peerview Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Clinical Care Options, EPG He. N. Fasnacht: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company . V. Soldatenkova: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. M.S. Xia: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. C. Duann: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Comany; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. J. Wright: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. D. Weiler-Bisig: Financial Interests, Personal, Invited Speaker, Speakers Bureau: Eli Lilly and Company; Financial Interests, Advisory Board: Eli Lilly and Company. M. Shah: Financial Interests, Institutional, Funding: Eli Lilly and Company, Eli Lilly and Company, Merck. All other authors have declared no conflicts of interest.