Abstract 1290P
Background
Selpercatinib (LOXO-292), a highly selective and potent RET kinase inhibitor, demonstrated marked and durable antitumor activity in pts with RET fusion+ NSCLC in an ongoing phase 1/2 trial. We evaluated best responses to last prior therapy received before enrollment and to selpercatinib by last prior therapy subgroups.
Methods
Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128) received the recommended phase 2 selpercatinib dose (160 mg twice daily) after dose escalation. This analysis assessed outcomes by category of last systemic therapy received prior to enrollment. Efficacy was analyzed in the first 105 consecutively enrolled pts pretreated with platinum chemotherapy (primary analysis set [PAS]). Adverse events (AEs) were measured in all pretreated pts who received selpercatinib by data cutoff date of 16-Dec-2019.
Results
PAS pts (n=105) had a median of 3 (range: 1-15) prior systemic regimens. Most pts received chemotherapy only (30%) or a multikinase inhibitor (MKI) (32%), and had an objective response rate (ORR) with these regimens of 13% and 18%, respectively (Table). ORR with selpercatinib was 64% (95% CI: 53.9-73.0) regardless of previous regimen type and ranged from 58% to 69% across prior therapy groups (Table). In the pretreated safety population (n=269), the most common treatment-related AEs reported in ≥1 prior therapy groups in ≥20% of pts were diarrhea, dry mouth, increased AST or ALT, rash, fatigue, thrombocytopenia, peripheral edema, increased blood creatinine or blood alkaline phosphate, and hypertension. Table: 1290P
| Prior Chemo Only (n=31) | Prior ICI Only (n=14) | Prior Chemo + ICI (n=10) | Prior MKI (n=34) | Prior Other Combination (n=16) | |
| Best response to last prior systemic therapy received before enrollment | |||||
| ORR, % | 13 | 7 | 20 | 18 | 13 |
| Best response (by IRC) to selpercatinib | |||||
| ORR, % (95% CI), n | 58 (39.1–75.5), 18 | 64 (35.1–87.2), 9 | 60 (26.2–87.8), 6 | 68 (49.5–82.6), 23 | 69 (41.3–89.0), 11 |
| DoR, median (95% CI), months | 18 (6.5, NE) | – (8.3, NE) | – (7.7, NE) | 12 (12.0, NE) | – (11.0, NE) |
| Duration of follow-up, median, months | 13 | 14 | 9 | 12 | 12 |
Abbreviations: Chemo, chemotherapy; DoR, duration of response; ICI, immune checkpoint inhibitor; IRC, independent review committee; MKI, multikinase inhibitor; NE, not evaluable; ORR, objective response rate.
Conclusions
Pts enrolled in LIBRETTO-001 did not experience clinically meaningful ORRs to varied therapies administered prior to selpercatinib. By contrast, selpercatinib showed consistent, robust, and durable efficacy across these varied prior therapy histories in heavily pretreated pts with RET fusion+ NSCLC. There were no new safety signals.
Clinical trial identification
EudraCT Number: 2017-000800-59. Date on which this record was first entered in the EudraCT database: 05-07-2018. Per Eli Lily and Company policy, results will be posted within 1 year of the primary outcome and trial completion actual dates. The estimated study completion date is May 2022 and the estimated primary completion date is March 2022.
Editorial acknowledgement
The authors acknowledge Karen Paulsrud, RPh, with Eli Lilly and Company, for editorial assistance in the writing of the abstract.
Legal entity responsible for the study
Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.
Funding
Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.
Disclosure
O. Gautschi: Advisory/Consultancy: Amgen. A. Drilon: Honoraria (self), Advisory/Consultancy: Ignyta, Genentech, Roche, Loxo, Bayer, Lilly, Takeda, Ariad, Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutic, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner, Elevatio; Research grant/Funding (institution): Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar, ; Research grant/Funding (self): Foundation Medicine; Licensing/Royalties: Wolters Kluwer; Travel/Accommodation/Expenses: Merck, Puma, Merus, Boehringer Ingelheim; Honoraria (self), CME: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, Peerview Institute, Paradigm Medical Communications, WebMD. D.S.W. Tan: Advisory/Consultancy: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer; Travel/Accommodation/Expenses: Pfizer, Boehringer Ingelheim, Roche; Honoraria (self): Bristol-Myers Squibb, Takeda, Novartis, Roche, Pfizer, Novartis; Research grant/Funding (institution): Novartis, GlaxoSmithKline, AstraZeneca. G.R. Oxnard: Advisory/Consultancy: AstraZeneca, Inivata, Takeda, Loxo, DropWorks, GRAIL, Janssen, Sysmex, Illumina, AbbVie, Merck; Licensing/Royalties, Patent pending entitled, \"Non-invasive blood-based monitoring of genomic alterations in cancer,\" on which Dr. Oxnard is a co-author.: Dana-Farber Cancer Institute; Honoraria (self): Sysmex, Guardant Health, Foundation Medicine. C. McCoach: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Travel/Accommodation/Expenses: Loxo, Lilly, Takeda; Research grant/Funding (self): Revolution Medicines. K. Goto: Advisory/Consultancy: Otsuka; Honoraria (self): Bristol-Myers Squibb, AstraZeneca, Pfizer, Chugai Pharma, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Lilly, Boehringer Ingelheim, Life Technologies, MSD, Nippon Kayaku, Takeda, Otsuka, IQVIA, Astellas Pharma, Guardant Health, Janssen, Kyowa Hakko; Research grant/Funding (self): MSD, AstraZeneca, Taiho Pharmaceutical, Chugai Pharma, Boehringer Ingelheim, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Takeda, Novartis, Daiichi Sankyo, Kyowa Hakko Kirin, Astellas Pharma, Eisai, Lilly, Pfizer, Riken Genesis, Bristol-Myers Squibb, Me. K. Park: Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim, Lilly, Hanmi, Novartis, Ono Pharmaceutical, Roche, Bristol-Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo, ; Speaker Bureau/Expert testimony: Boehringer Ingelheim, AZD; Research grant/Funding (self): AstraZeneca, MSD Oncology. F. de Braud: Advisory/Consultancy: Ignyta, BMS, Daiichi Sankyo, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono, Sanofi, NMS Neviano Medical Science, Pharm Research Associated (U.K.) Ltd.; Speaker Bureau/Expert testimony: BMS, Roche, MSD, Ignyta, Bayer, ACCMED, Dephaforum S.r.l., Nadirex, Merck, Biotechspert Ltd, PriME Oncology, Pfizer, Servier, Celgene, Tesaro, Loxo Oncology Inc., Sanofi, Healthcare Research & Pharmacoepidemiology; Research grant/Funding (self): Novartis, Roche, BMS, Celgene, Incyte, NMS, Merck KGAA, Kymab, Pfizer, Tesaro, MSD. P. French: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. V. Soldatenkova: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. B. Besse: Research grant/Funding (institution): AstraZeneca, Pfizer, Lilly, Onxeo, Bristol-Myers Squibb, Inivata, AbbVie, Amgen, Blueprint Medicines, Celgene, GlaxoSmithKline, Ignyta, Ipsen, Merck KGaA, MSD Oncology, Nektar, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Therapeutics, Cri. All other authors have declared no conflicts of interest.