Found 1 Presentation For Request "27P"
Presentation Topic
  • Advanced NSCLC
 Filtered By

Advanced NSCLC

27P - Durability of efficacy and safety with selpercatinib in patients (pts) with RET Fusion+ non-small cell lung cancer (NSCLC) (ID 5126)

Speakers
  • Alexander Drilon (New York, NY, United States of America)
Authors
  • Alexander Drilon (New York, NY, United States of America)
  • Vivek Subbiah (Houston, TX, United States of America)
  • Oliver Gautschi (Luzern, Switzerland)
  • Pascale Tomasini (Dijon, France)
  • Filippo Guglielmo Maria De Braud (Milan, Italy)
  • Ben Solomon (Melbourne, Australia)
  • Daniel Shao-Weng Tan (Singapore, Singapore)
  • Guzman Alonso (Barcelona, Spain)
  • Jurgen Wolf (Köln, Germany)
  • Keunchil Park (Seoul, Korea, Republic of)
  • Koichi Goto (Kashiwa, Chiba, Japan)
  • Victoria Soldatenkova (Indianapolis, IN, United States of America)
  • Sylwia Szymczak (Indianapolis, IN, United States of America)
  • Scott Barker (Indianapolis, IN, United States of America)
  • Tarun Puri (Indianapolis, IN, United States of America)
  • Aimee B. Lin (Indianapolis, IN, United States of America)
  • Herbert Ho Fung Loong (Sha Tin, Hong Kong PRC)
  • Benjamin Besse (Villejuif, France)

Abstract

Background

Selpercatinib, a first-in-class highly selective and potent CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ NSCLC. In prior reports, follow-up was limited and duration of response (DoR) and progression-free survival (PFS) were ongoing and immature.

Methods

Updated analysis of selpercatinib in pts with RET fusion+ NSCLC in LIBRETTO-001 (NCT03157128) was conducted with a 15-month (mo) interval between the preceding and current analyses. Primary endpoint was objective response rate (ORR, RECIST 1.1) by independent review committee (IRC). Secondary endpoints included DoR, PFS, clinical benefit rate (CBR; CR+PR+SD ≥16 weeks), OS, and safety.

Results

Efficacy results from treatment naïve pts (N=69) and pts previously treated with platinum chemotherapy (N=247) are shown (Table). Despite a median follow-up (f/u) of ∼24 mo in the treatment naïve and platinum chemotherapy pretreated populations, median DoR (mDoR) and PFS (mPFS) estimates are still not mature. Among all NSCLC pts, 26 had measurable CNS metastases at baseline per IRC. Selpercatinib treatment resulted in a CNS ORR of 84.6% (95% CI: 65.1–95.6), with a CNS mDoR of 9.4 mo (95%CI: 7.4–15.3) at a median f/u of 25.8 mo. In the safety population (NSCLC pts with ≥ 1 dose, N=356), the most common adverse events (AEs in ≥25% pts) were dry mouth, diarrhea, hypertension, increased ALT/AST, peripheral edema, constipation, rash, headache, and fatigue. In total, 34 pts (9.6%) discontinued treatment due to AEs, including 11 pts (3.1%) due to drug-related AEs per investigator.

By IRC Prior platinum chemotherapy Treatment naïve
% (95% CI) 30Mar20 N=218 15Jun21 N=247 30Mar20 N=48 15Jun21 N=69
ORR 56.9 (50.0–63.6) 61.1 (54.7–67.2) 85.4 (72.2–93.9) 84.1 (73.3–91.8)
CBR 84.4 (78.9–89.0) 85.4 (80.4–89.6) 93.8 (82.8–98.7) 92.8 (83.9–97.6)
mDoR, mo (95% CI) 17.5 (12.1–NE) 28.6 (20.4–NE) NE (12.0–NE) 20.2 (13.0–NE)
Censoring, % 69.4 60.9 75.6 55.2
Median f/u, mo 12.0 21.2 9.8 20.3
12mo DoR 69.1 (58.1–77.8) 73.1 (64.9–79.7) 65.0 (42.8–80.3) 66.1 (51.6–77.3)
mPFS, mo (95% CI) 19.3 (16.5–NE) 24.9 (19.3–NE) NE (13.8–NE) 22.0 (13.8–NE)
Censoring, % 66.1 55.9 70.8 53.6
Median f/u, mo 13.6 24.7 10.8 21.9
12mo PFS 69.7 (62.2–75.9) 70.5 (64.1–76.0) 67.6 (49.5–80.3) 70.6 (57.8–80.2)

Conclusions

With longer follow-up and additional patients, selpercatinib demonstrates durable efficacy and intracranial activity regardless of line of therapy. The safety profile of selpercatinib remains consistent with prior reports.

Clinical trial identification

NCT03157128.

Editorial acknowledgement

Medical writing assistance was provided by Kristi Gruver, an employee of Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

A. Drilon: Financial Interests, Personal, Advisory Board, Honoraria/Advisory Boards: 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 Onco; Financial Interests, Institutional, Research Grant, Associated research paid to institution: Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar; Financial Interests, Personal, Research Grant: Foundation Medicine; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, Food/Beverage: Merck, Puma, Merus, Boehringer Ingelheim; Financial Interests, Personal, Other, CME Honoraria: 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. V. Subbiah: Financial Interests, Personal, Research Grant, Grant/Research Support: National Institutes of Health grant R01CA242845, Loxo Oncology/Eli Lilly, Novartis, Bayer, Berghealth, Incyte, Fujifilm, PharmaMar, D3, Pfizer, Multivir, Amgen, AbbVie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Med; Financial Interests, Personal, Advisory Board, Advisor/Board Member: Helsinn, Loxo Oncology/Eli Lilly, R-Pharma US, INCYTE, QED Pharma, MedImmune, Novartis. O. Gautschi: Financial Interests, Personal, Other, Consultant; all honoraria paid to institution: Amgen and Lilly, advisory boards for AstraZeneca, Merck, Amgen and Lilly. P. Tomasini: Financial Interests, Personal, Expert Testimony, Honoraria for expert testimony: AstraZeneca, Roche, Takeda, JNJ, AbbVie, Bristol Myers Squibband BI. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Healthcare Research & Pharmacoepidemiology, Merck Group, ACCMED, Nadirex, MSD, Pfizer, Servier, Sanofi, Roche, Amgen, Incyte, Dephaforum; Financial Interests, Personal, Advisory Board, Consultant or advisory board: Roche, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, Bristol Myers Squibb, Menarini, Astra Zeneca; Financial Interests, Personal, Principal Investigator: Novartis, F.Hoffmann-LaRoche Ltd, Bristol Myers Squibb, Ignyta Operating INC, MSD Spa, Kymab, Pfizer, Tesaro, MSD, MedImmune LCC, Exelixis Inc., LOXO Oncology Incorporated, DAICHI SANKIO Dev. Limited, Basilea Pharmaceutica International AG, Janssen-Cilag I. B. Solomon: Financial Interests, Personal, Advisory Board, Advisory Boards/Honoraria: Eli Lilly, Pfizer, Roche/Genentech, Novartis, Takeda, AstraZeneca, Merck Sharpe Dohme, Bristol Myers Squibb, Amgen, BeiGene. D. Shao-Weng Tan: Financial Interests, Personal, Other, Honoraria: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, Astra Zeneca, Eli-lily, Loxo, GlaxoSmithKlein, MSD; Financial Interests, Institutional, Research Grant, Research grant/funding to institution: Novartis, Astra Zeneca, Bayer, Pfizer, Amgen. J. Wolf: Financial Interests, Personal, Advisory Board, Advisory boards and lecture fees: Amgen, AstraZeneca, Bayer, Blueprint, Bristol Myers Squibb, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Institutional, Research Grant, Research support to institution: Bristol Myers Squibb, Janssen Pharmaceutica, Novartis, Pfizer. K. Park: Financial Interests, Personal, Advisory Board, Advisor: Eli Lilly and Company. K. Goto: Financial Interests, Personal, Research Grant: Eli Lilly and Company, Japan KK; Financial Interests, Personal, Advisory Board, Advisory/Consultancy, and Honoraria: Eli Lilly and Company and Japan KK. V. Soldatenkova: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. S. Szymczak: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. S. Barker: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. T. Puri: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. A.B. Lin: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. H.H.F. Loong: Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim, Celgene, Eli Lilly, Illumina, Novartis, Merck Sereno, Takeda, George Clinical; Financial Interests, Personal, Speaker’s Bureau: AbbVie, Bayer, Eisai, Eli Lilly, Guardant Health, Novartis; Financial Interests, Personal, Other, Travel Support: Bayer, Boehringer-Ingelheim, MSD, Novartis, Pfizer; Financial Interests, Personal, Research Grant, Research funding: MSD, Mundipharma, Novartis; Financial Interests, Personal, Other: Member, Pharmacy and Poisons (Registration of Pharmaceutical Products and Substances: Certification of Clinical Trial/Medicinal Test) Committee, Pharmacy & Poisons Board of Hong Kong. B. Besse: Financial Interests, Personal, Other: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genen. All other authors have declared no conflicts of interest.

Collapse