Abstract 1413TiP
Background
Platinum-based chemotherapy +/- an immune checkpoint inhibitor, the current standard of care in patients (pts) with RET+ NSCLC, does not account for underlying oncogenic drivers. In the LIBRETTO-001 phase 1/2 trial, selpercatinib (Loxo-292), a selective and potent RET inhibitor, demonstrated antitumor activity [objective response rate (ORR) 85%] with a tolerable profile in pts with Tx-naïve, RET+ NSCLC. This global, open-label, randomized, controlled, phase 3 trial will evaluate selpercatinib vs platinum-based and pemetrexed (pem) Tx with or without pembrolizumab (+/-pembro) in Tx-naïve pts with advanced or metastatic RET+ non-squamous NSCLC.
Trial design
Pts will be randomized to Arm A: selpercatinib 160 mg BID in continuous 3 week (wk) cycles or Arm B: pem (500 mg/m2 IV) in 3 wk cycles plus investigator’s choice of carboplatin (carbo) (AUC 5) or cisplatin (cis) (75 mg/m2 IV) for 4 cycles. For Arm B, at the investigator’s discretion, pembro (200 mg IV) may also be given for up to 35 cycles and pts may receive maintenance pem +/-pembro. Crossover is allowed for Arm B pts who progress. Tx will continue until PD, unacceptable toxicity, decision to withdraw or death. Stratification factors are geography: East vs non-East Asian, brain metastases: yes vs no and intended Tx for Arm B: +/-pembro. Eligibility criteria are age ≥18 years; Tx-naïve; non-squamous Stage IIIB-IIIC not suitable for surgery/radiation therapy or Stage IV NSCLC; RET+ identification by PCR or NGS (tumor) or NGS (blood); measurable disease by RECIST 1.1; ECOG performance status 0-2. Key exclusion criteria are presence of other oncogenic drivers or symptomatic CNS metastases. Efficacy assessments will be performed until PD, the start of a new anticancer Tx, death or study completion. The primary endpoint is progression free survival (PFS) per RECIST 1.1 by independent review. Investigator assessed PFS, ORR/duration of response (DOR), intracranial ORR/DOR, overall survival (OS), time to deterioration in pulmonary symptoms, PFS2, RET fusion status: local vs central, safety and pharmacokinetics are secondary endpoints.
Clinical trial identification
NCT04194944.
Editorial acknowledgement
Hannah Davis, PhD, an Eli Lilly and Company employee, provided medical writing support.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
H.H.F. Loong: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene ; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Guardant Health; Speaker Bureau/Expert testimony: Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck, Sharp & Dohme; Research grant/Funding (institution): Mundipharma; Travel/Accommodation/Expenses: Pfizer. K. Goto: Honoraria (self), Research grant/Funding (self): Astellas Pharma Inc; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self), Research grant/Funding (self): Daiichi Sankyo; Honoraria (self): Guardant Health Inc; Honoraria (self): IQVIA Services Japan K.K.; Honoraria (self), Research grant/Funding (self): Janssen Pharmaceutical K.K. ; Honoraria (self), Research grant/Funding (self): Kyowa Hakko Kirin Co.,Ltd; Honoraria (self), Research grant/Funding (self): Life Technologies; Honoraria (self), Research grant/Funding (self): Lilly; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Nippon Kayaku; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Honoraria (self): Otsuka Pharmaceutica; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (self): Takeda; Advisory/Consultancy: Otsuka; Research grant/Funding (self): Amgen Inc; Research grant/Funding (self): Loxo; Research grant/Funding (self): Medical & Biological Laboratories Co., Ldt.; Research grant/Funding (self): Merck Serono; Research grant/Funding (self): Riken Genesis; Research grant/Funding (self): Sumitomo Dainippon; Research grant/Funding (self): Sysmex Corporation; Research grant/Funding (self): Xcoo. B. Solomon: Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Amgen. F.C. Santini: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp Dohme; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Lilly; Honoraria (self): Roche; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis. V. Soldatenkova: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly & Company. A. Sashegyi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly & Company. A. Bence Lin: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly & Company. B.K. Lin: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. Wolf: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Janssen; Advisory/Consultancy: Loxo/Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Blueprint Medicines. G.R. Oxnard: Honoraria (self): Foundation Medicine; Honoraria (self): Guardant Health; Honoraria (self): Sysmex; Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: DropWorks; Advisory/Consultancy: GRAIL; Advisory/Consultancy: Illumina; Advisory/Consultancy: Inivata; Advisory/Consultancy: Janssen; Advisory/Consultancy: Loxo; Advisory/Consultancy: Merck; Advisory/Consultancy: Sysmex; Advisory/Consultancy: Takeda; Licensing/Royalties: Patent by DFCI, \"Non-invasive blood-based monitoring of genomic alterations in cancer\", on which I am a co-author. C. Zhou: Speaker Bureau/Expert testimony: Lilly China; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Hengrui; Advisory/Consultancy, Speaker Bureau/Expert testimony: Qilu; Advisory/Consultancy, Speaker Bureau/Expert testimony: Innovent Biologics; Speaker Bureau/Expert testimony: LUYE Phiosciences Inc; Speaker Bureau/Expert testimony: Amoy Diagnostics; Advisory/Consultancy: Topalliance Biosciences Inc. A. Drilon: Honoraria (self), Research grant/Funding (self): Foundation Medicine; Honoraria (self): Medscape; Honoraria (self), Advisory/Consultancy: MORE Health; Honoraria (self): OncLive; Honoraria (self): Peerview; Honoraria (self): PeerVoice; Honoraria (self): Physicians Education Resources; ; Honoraria (self): Research to Practice; Honoraria (self): Targeted Oncology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BeiGene; Advisory/Consultancy: BerGenBio; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Helsinn Therapeutics; Advisory/Consultancy: Hengrui Therapeutics; Advisory/Consultancy: Ignyta; Advisory/Consultancy: Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda/Ariad/Millenium; Advisory/Consultancy: TP Therapeutics; Advisory/Consultancy: Tyra Biosciences; Advisory/Consultancy: Verastem. K. Park: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Hanmi; Advisory/Consultancy: Lilly; Advisory/Consultancy: Loxo: Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: AZ; Research grant/Funding (self): MSD Oncology. All other authors have declared no conflicts of interest.