Abstract 35P
Background
Selpercatinib is a highly selective and potent CNS-active RET kinase inhibitor approved for the treatment of RET fusion-positive NSCLC based on the results of the phase I/II trial LIBRETTO-001 (NCT03157128). The final LIBRETTO-001 data for NSCLC is reported.
Methods
Patients with advanced, RET fusion-positive (identified by NGS, PCR or FISH) NSCLC who were treatment naïve or who had previously received platinum-based chemotherapy were enrolled at a selpercatinib dose of 160 mg BID. The primary end point was objective response rate (ORR) by RECIST 1.1 assessed by an independent review committee. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety.
Results
In 69 treatment naïve patients, the ORR was 83% with a mDoR of 20.3 mo (median follow-up 37.1 mo) and mPFS of 22.0 mo (Table). In 247 patients who had previously received platinum-based chemotherapy, the ORR was 62% with a mDoR of 31.6 mo (median follow-up 39.5 mo) and mPFS of 26.2 mo. Across both groups, 26 patients had measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-mDoR of 9.4 mo (median follow up 25.8 mo) and CNS-mPFS of 11.0 mo. At the 36 mo landmark estimate, 57% of previously treated patients and 66% of treatment naïve patients were alive. The overall safety profile was consistent with previous reports. The most common adverse events (AEs) ≥G3 in ≥10% patients were hypertension and increased AST/ALT. Dose reduction from any cause occurred in 53% of patients. In total 11% discontinued treatment due to AEs, including 4% due to AEs related to selpercatinib as assessed by the investigator. Table: 35P
| Previously treated with platinum-based chemotherapy N=247 | Treatment naïve N=69 | |
| ORR, % (95% CI) | 62 (55, 68) | 83 (72, 91) |
| mTime to Response, mo | 1.9 | 1.8 |
| mDoR, mo (95% CI) | 31.6 (20.4, 42.3) | 20.3 (15.4, 29.5) |
| Censoring, % | 49.3 | 43.9 |
| Median follow-up, mo | 39.5 | 37.1 |
| 36 mo DoR, % | 44.7 (35.7, 53.4) | 35.4 (22.0, 49.0) |
| mPFS, mo (95% CI) | 26.2 (19.3, 35.7) | 22.0 (16.5, 24.9) |
| Censoring, % | 46.2 | 44.9 |
| Median follow-up, mo | 41.2 | 38.9 |
| 36 mo PFS, % | 41.1 (34.2, 47.9) | 34.6 (22.3, 47.3) |
| mOS, mo (95% CI) | 47.6 (35.9, NE) | NE (37.8, NE) |
| Censoring, % | 55.5 | 62.3 |
| Median follow-up, mo | 44.6 | 41.9 |
| 36 mo OS, % | 56.6 (49.8, 62.8) | 65.6 (52.4, 75.9) |
Conclusions
In the final analysis, selpercatinib continued to show durable responses and intracranial activity with a manageable safety profile in patients with RET fusion-positive NSCLC. These data and the recent positive results from the phase III trial LIBRETTO-431, reinforce the importance of genomic testing to identify RET fusions at initial diagnosis.
Clinical trial identification
NCT03157128.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company. Dr. Drilon was supported by the National Cancer Institute/National Institutes of Health P30CA008748, 1R01CA251591001A1, and 1R01CA273224-01, and Lungevity grants.
Disclosure
O. Gautschi: Financial Interests, Institutional, Other, Consultant: Amgen, Lilly; Financial Interests, Institutional, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Invited Speaker: Lilly. A. Drilon: Financial Interests, Personal, Advisory Board: 14ner/Elevation Oncology, AbbVie, Amgen, ArcherDX, AstraZeneca, BeiGene, BerGenBio, Blueprint Medicines, EcoR1, Exelixis, Helsinn, Hengrui Therapeutics, Ignyta/Genentech/Roche, Janssen, Liberum, Loxo/Bayer/Lilly, Melendi, Monopteros, Monte Rosa, Novartis, Pfizer, Remedica Ltd., TP Therapeutics, Takeda/Ariad/Millennium, Tyra Biosciences, Verastem Oncology; Financial Interests, Personal, Other, CME: AiCME, Clinical Care Options, MJH Life Sciences, Med Learning, Medscape, Medscape, Onclive, Paradigm Medical Communications, PeerView Institute, PeerVoice, Physicians Education Resources, Targeted Oncology, WebMD; Financial Interests, Personal, Other, Consulting: Applied Pharmaceutical Science, Inc, EPG Health, Entos, Harborside Nexus, Merus, Nuvalent, Ology, Prelude, TouchIME, Treeline Bio, mBrace; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, RV More, Remedica Ltd; 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, PharmaMar, GSK, Teva, Taiho; Financial Interests, Personal, Funding, Research: Foundation Medicine; Non-Financial Interests, Personal, Member: ASCO, AACR, IASLC; Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus; Other, Personal, Other, Other: Boehringer Ingelheim. B. 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, Invited Speaker, Principal Investigator and Steering committee Chair: Roche/Genentech, Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis. P. Tomasini: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Lilly, Janssen, Amgen, Takeda; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Janssen, Amgen, Lilly, Takeda. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli-Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. Tomasini: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Lilly, Janssen, Amgen, Takeda; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Janssen, Amgen, Lilly, Takeda. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte,MSD, Merck Group, Nadirex, Pfizer, Roche, Sanofi, Seagen, Servier, Ambrosetti, BMS, Basilea Pharmaceutica International AG, Daiichi Sankyo Dev. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, MSD, Merck Group, Nadirex, Pfizer, Roche, Sanofi, Seagen, Servier, Ambrosetti, BMS, Basilea Pharmaceutica International AG, Daiichi Sankyo Dev. Limited, Exelixis Inc, F.Hoffmann-LaRoche Ltd, IQVIA, Ignyta Operating INC, Janssen-Cilag International NV, Kymab, LOXO Oncology Incorporated, MSD, MedImmune LCC, Merck KGAA, Merck Sharp & Dohme Spa, Novartis, Pfizer, Tesaro; Financial Interests, Personal, Other, Consultant: Mattioli 1885; Financial Interests, Personal, Other, Think Thank: MCCann Health; Financial Interests, Personal, Other, Consultant Advisory Board: AstraZeneca, BMS, EMD Serono, Incyte, MSD, Menarini, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Other, Consultant Adv Board: Taiho. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Taiho Pharmaceutical Co., Ltd., Syneos Health Clinical K.K., Life Technologies Japan Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K., Haihe Biopharma Co., Ltd.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., LTD., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical ＆ Biological Laboratories Co., LTD., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K., Craif Inc., Pfizer R&D Japan G.K., Turning Point Therapeutics,Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. P. Peterson, S. Barker, K. Liming, B. Frimodt-Moller: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. K. Park: Financial Interests, Personal, Advisory Board: JNJ, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, DMC member: BeiGene, Incyte; Financial Interests, Personal, Other, Advisor/Consultant: Genius, IMBdx; Financial Interests, Personal, Other, Advisor: Abion; Financial Interests, Personal, Stocks/Shares, Stock option: IMBDx, Genius.