A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer (LIBRETTO-431)

October 17, 2025 updated by: Eli Lilly and Company

LIBRETTO-431: A Multicenter, Randomized, Open-Label, Phase 3 Trial Comparing Selpercatinib to Platinum-Based and Pemetrexed Therapy With or Without Pembrolizumab as Initial Treatment of Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

The reason for this study is to see if the study drug selpercatinib compared to a standard treatment is effective and safe in participants with rearranged during transfection (RET) fusion-positive non-squamous non-small cell lung cancer (NSCLC) that has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

261

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad de Buenos Aires, Argentina, C1426ANZ
        • Alexander Fleming
      • San Juan, Argentina, 5400
        • Clínica El Castaño
    • Buenos Aires
      • Berazategui, Buenos Aires, Argentina, B1884BBF
        • Centro de Oncología e Investigación de Buenos Aires
      • Caba, Buenos Aires, Argentina, 1125
        • Fundacion CENIT para la investigación en Neurociencias
    • Río Negro Province
      • Viedma, Río Negro Province, Argentina, R8500ACE
        • Clinica Viedma
  • Australia
      • Frankston, Australia, 3199
        • Peninsula Oncology Centre
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
      • Melbourne, Victoria, Australia, 3065
        • St Vincent's Hospital
  • Belgium
      • Ghent, Belgium, 9000
        • UZ Gent Hospital
      • Mechelen, Belgium, 2800
        • AZ Sint-Maarten, Campus Leopoldstraat 2
      • Namur, Belgium, 5000
        • CHU UCL Namur/Site Sainte Elisabeth
    • Bruxelles-Capitale, Région de
      • Brussels, Bruxelles-Capitale, Région de, Belgium, 1090
        • UZ Brussel
    • Oost-Vlaanderen
      • Sint-Niklaas, Oost-Vlaanderen, Belgium, B-9100
        • AZ Nikolaas
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • UZ Leuven
    • West Flanders
      • Roeselare, West Flanders, Belgium, 8800
        • AZ Delta
  • Brazil
      • Rio de Janeiro, Brazil, 20231-050
        • Instituto Nacional de Câncer - INCA
      • Rio de Janeiro, Brazil, 22250-905
        • Centro de Tratamento de Tumores Botafogo para Oncoclinicas Rio de Janeiro SA
      • São Paulo, Brazil, 01308-060
        • Hospital Sírio Libanês
      • São Paulo, Brazil, 01246000
        • Icesp - Instituto Do Câncer Do Estado de São Paulo
    • Brazil
      • São Paulo, Brazil, Brazil, 01308-060
        • Hospital Sírio Libanês
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 40170-070
        • Nucleo de Oncologia da Bahia
    • Paraná
      • Londrina, Paraná, Brazil, 86015-520
        • Hospital de Cancer de Londrina
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Hospital Sao Lucas da PUCRS
    • Rio de Janeiro
      • Rio de Janeiro, Rio de Janeiro, Brazil, 22775-001
        • Grupo COI - Clínicas Oncológicas Integradas
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Fundação Pio XII - Hospital de Câncer de Barretos
      • São Paulo, São Paulo, Brazil, 04543-000
        • Instituto D'Or de Pesquisa e Ensino (IDOR)
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
  • China
      • Hangzhou, China, 310003
        • First Affiliated Hosp of College of Med, Zhejiang University
      • Shanghai, China, 200030
        • Shanghai Chest Hospital
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Beijing Cancer hospital
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou
      • Guangzhou, Guangzhou, China, 510120
        • The First Affiated Hospital Of Guangzhou Medical Collage
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Harbin Medical University Cancer Hospital
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Wuhan Union Hospital
    • Hunan
      • Changsha, Hunan, China, 410013
        • Hunan Cancer Hospital
      • Changsha, Hunan, China, 410005
        • Hunan Provincial People's Hospital
    • Jiangsu
      • Changzhou, Jiangsu, China
        • Changzhou No.2 People's Hospital
    • Jilin
      • Changchun, Jilin, China
        • Jilin Cancer Hospital
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200433
        • Shanghai Pulmonary Hospital
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China Hospital of Sichuan University
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830000
        • Xinjiang Medical University Cancer Hospital - Urumqi
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Zhejiang Cancer Hospital
  • Czechia
      • Olomouc, Czechia, 779 00
        • Fakultni nemocnice Olomouc
      • Ostrava - Vitkovice, Czechia, 70384
        • Nemocnice AGEL Ostrava - Vitkovice a.s.
      • Prague, Czechia, 180 81
        • Fakultni nemocnice Bulovka
  • France
      • Paris, France, 75014
        • Hopitaux Universitaires Paris Centre-Hopital Cochin
    • Auvergne-Rhône-Alpes
      • Lyon, Auvergne-Rhône-Alpes, France, 69373
        • Centre Leon Berard
    • Bouches-du-Rhône
      • Marseille, Bouches-du-Rhône, France, 13385
        • Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
    • Hérault
      • Montpellier, Hérault, France, 34298
        • Institut regional du Cancer Montpellier
    • Isère
      • La Tronche, Isère, France, 38700
        • CHU Grenoble Alpes
    • Puy-de-Dôme
      • Clermont-Ferrand, Puy-de-Dôme, France, 63011
        • Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
  • Germany
      • Berlin, Germany, 12203
        • Charité Universitätsmedizin Berlin Campus Benjamin Franklin
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69126
        • Thoraxklinik-Heidelberg gGmbH
    • Bavaria
      • Gauting, Bavaria, Germany, 82131
        • Asklepios Fachkliniken München-Gauting
      • Immenstadt im Allgäu, Bavaria, Germany, 87509
        • Klinikverbund Kempten-Oberallgäu
    • Lower Saxony
      • Georgsmarienhütte, Lower Saxony, Germany, 49124
        • Franziskus-Hospital Harderberg
      • Göttingen, Lower Saxony, Germany, 37075
        • Universitatsmedizin Gottingen
    • North Rhine-Westphalia
      • Cologne, North Rhine-Westphalia, Germany, 50937
        • University Hospital of Cologne
    • Schleswig-Holstein
      • Großhansdorf, Schleswig-Holstein, Germany, 22927
        • LungenClinic Grosshansdorf
  • Greece
    • Attikí
      • Athens, Attikí, Greece, 115 27
        • Sotiria Thoracic Diseases Hospital of Athens
    • Krítí
      • Heraklion, Krítí, Greece, 711 10
        • University General Hospital of Heraklion
    • Thessaloníki
      • Thessaloniki, Thessaloníki, Greece, 570 01
        • European Interbalkan Medical Center
      • Thessaloniki, Thessaloníki, Greece, 570 10
        • G. Papanikolaou General Hospital
  • Hong Kong
      • Shatin, Hong Kong, 852
        • Prince of Wales Hospital
    • Kowloon
      • Jordan, Kowloon, Hong Kong, 999077
        • Hong Kong United Oncology Centre
  • Israel
      • Beersheba, Israel, 8400000
        • Soroka Medical Center
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center
      • Ramat Gan, Israel, 5262100
        • Sheba Medical Center
    • Ḥeifā
      • Haifa, Ḥeifā, Israel, 3109601
        • Rambam Health Care Campus
  • Italy
      • Avellino, Italy, 83100
        • Azienda Ospedaliera San Giuseppe Moscati
      • Bologna, Italy, 40138
        • IRCCS - AOU di Bologna
      • Pisa, Italy, 56126
        • Azienda Ospedaliera Universitaria Pisana
      • Roma, Italy, 00144
        • Istituto Nazionale Tumori Regina Elena
    • Campania
      • Napoli, Campania, Italy, 80131
        • Istituto Nazionale Tumori Irccs Fondazione Pascale
    • Emilia-Romagna
      • Ravenna, Emilia-Romagna, Italy, 48121
        • Ospedale Santa Maria delle Croci
    • Friuli Venezia Giulia
      • Aviano, Friuli Venezia Giulia, Italy, 33081
        • Cro-Irccs
    • Lazio
      • Rome, Lazio, Italy, 00152
        • Azienda Ospedaliera San Camillo Forlanini
      • Rome, Lazio, Italy, 00168
        • Fondazione Policlinico Universitario Agostino Gemelli
    • Lombardy
      • Monza, Lombardy, Italy, 20900
        • Ospedale San Gerardo-ASST Monza
    • Milano
      • Milan, Milano, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda
      • Rozzano, Milano, Italy, 20089
        • Humanitas
    • Torino
      • Orbassano, Torino, Italy, 10043
        • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
  • Japan
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Japan, 541-8567
        • Osaka International Cancer Institute
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 003-0804
        • National Hospital Organization Hokkaido Cancer Center
    • Ishikawa-ken
      • Kanazawa, Ishikawa-ken, Japan, 920-8641
        • Kanazawa University Hospital
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 241-8515
        • Kanagawa cancer center
    • Osaka
      • Osaka Sayama-shi, Osaka, Japan, 589 8511
        • Kindai University Hospital- Osakasayama Campus
    • Shizuoka
      • Nakatogari, Shizuoka, Japan, 411-8777
        • Tominaga Hospital
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Koto, Tokyo, Japan, 135-8550
        • Japanese Foundation for Cancer Research
    • Tottori
      • Yonago, Tottori, Japan, 683-8504
        • Tottori University Hospital
  • Mexico
      • San Luis Potosí City, Mexico, 78209
        • Oncologico Potosino, S.C.
    • Federal District
      • Mexico City, Federal District, Mexico, 03100
        • Health Pharma Professional Research S.A. de C.V:
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44680
        • Actualidad Basada En La Investigacion Del Cancer
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Amsterdam UMC, Locatie VUMC
    • Gelderland
      • Harderwijk, Gelderland, Netherlands, 3844 DG
        • Ziekenhuis St. Jansdal
    • North Brabant
      • 's-Hertogenbosch, North Brabant, Netherlands, 5223 GZ
        • Jeroen Bosch Hospital
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 CE
        • Erasmus Medisch Centrum
  • Poland
      • Gdansk, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne
      • Warsaw, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
  • Romania
      • Bucharest, Romania, 050098
        • Spitalul Universitar de Urgenta Bucuresti
      • Cluj-Napoca, Romania, 400015
        • Institutul Oncologic
      • Suceava, Romania, 720237
        • Spitalul Județean Sfântul Ioan cel Nou Suceava
    • București
      • Bucharest, București, Romania, 22328
        • Institutul Oncologic
      • Bucharest, București, Romania, 031422
        • Gral Medical Diagnostic Center
    • Constanța County
      • Constanța, Constanța County, Romania, 900591
        • Constanta County Emergency Clinical Hospital Sf.Ap.Andrei
    • Timiș County
      • Timișoara, Timiș County, Romania, 300239
        • Cabinet Medical Oncomed
  • Russia
      • Arkhangelsk, Russia, 163045
        • Arkhangelsk Clinical Oncological Dispensary
      • Kazan', Russia, 420029
        • Republican Clinical Oncology Dispensary
      • Moscow, Russia, 119991
        • First Moscow State Medical University I.M. Sechenov
      • Moscow, Russia, 121205
        • Hadassah Medical
    • Baškortostan, Respublika
      • Ufa, Baškortostan, Respublika, Russia, 450054
        • GBUZ Republican Clinical Oncological Dispensary
    • Kalužskaja Oblast
      • Kaluga, Kalužskaja Oblast, Russia, 248007
        • Kaluga Regional Clinical Oncology Center
    • Murmansk Oblast
      • Murmansk, Murmansk Oblast, Russia, 183047
        • Murmansk Regional Clinical Hospital P.A. Bayandina
    • Samara Oblast
      • Samara, Samara Oblast, Russia, 443031
        • Samara Regional Clinical Oncology Center
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russia, 197758
        • Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (oncological) named afte -T
      • Saint Petersburg, Sankt-Peterburg, Russia, 197758
        • Scientific research institution of oncology named after N.N. Petrov
  • Singapore
      • Singapore, Singapore, 308433
        • Tan Tock Seng Hospital
  • South Korea
      • Daejeon, South Korea, 35365
        • Konyang University Hospital
      • Seoul, South Korea, 06351
        • Samsung Medical Center
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, South Korea, 10408
        • National Cancer Center
      • Seongnam-si, Gyeonggi-do, South Korea, 13620
        • Seoul National University Bundang Hospital
    • Korea
      • Incheon, Korea, South Korea, 21565
        • Gachon University Gil Medical Center
      • Seoul, Korea, South Korea, 05505
        • Asan Medical Center
    • Kyǒngsangnam-do
      • Jinju, Kyǒngsangnam-do, South Korea, 52727
        • Gyeongsang National University Hospital
    • Seoul, Korea
      • Seoul, Seoul, Korea, South Korea, 03080
        • Seoul National University Hospital
    • Seoul-teukbyeolsi [Seoul]
      • Dongjak-gu, Seoul-teukbyeolsi [Seoul], South Korea, 07061
        • Boramae Medical Center
  • Spain
      • Alicante, Spain, 03010
        • Hospital General Universitario de Alicante
      • Barcelona, Spain, 08028
        • Hospital Universitari Dexeus
      • Barcelona, Spain, 8041
        • Hospital De La Santa Creu I Sant Pau
      • Barcelona, Spain, 08908
        • Instituto Catalán de Oncología - Hospital Duran i Reynals
      • Barcelona, Spain, 08003
        • Parc de Salut Mar - Hospital del Mar
      • Jaén, Spain, 23007
        • Complejo Hospitalario de Jaen
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28027
        • Clinica Universidad de Navarra
      • Málaga, Spain, 29011
        • Hospital Regional Universitario
      • Pamplona, Spain, 31009
        • Complejo Hospitalario de Navarra
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Seville, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Valencia, Spain, 46026
        • Hospital Universitari i Politècnic La Fe
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
    • Balearic Islands
      • Palma de Mallorca, Balearic Islands, Spain, 07198
        • Hospital Fundacion Son Llatzer
    • Barcelona [Barcelona]
      • Badalona, Barcelona [Barcelona], Spain, 08916
        • Institut Català d'Oncologia (ICO) - Badalona
    • Galicia [Galicia]
      • Santiago de Compostela, Galicia [Galicia], Spain, 15706
        • CHUS - Hospital Clinico Universitario
    • Las Palmas
      • Las Palmas de Gran Canaria, Las Palmas, Spain, 35016
        • Hospital Insular de Gran Canaria
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro Majadahonda
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Clinica Universitaria De Navarra
  • Taiwan
      • Kaohsiung City, Taiwan, 82445
        • E-Da Hospital
      • Kaohsiung City, Taiwan, 83301
        • Chang Gung Memorial Hospital at Kaohsiung
      • Neihu Taipei, Taiwan, 114
        • Tri-Service General Hospital
      • New Taipei City, Taiwan, 235
        • Taipei Medical University Shuang Ho Hospital
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Taichung, Taiwan, 402
        • Chung Shan Medical University Hospital
      • Taichung, Taiwan, 407
        • Taichung Veterans General Hospital
      • Tainan City, Taiwan, 73657
        • Chi Mei Hospital - Liouying Branch
      • Tainan City, Taiwan, 704
        • National Cheng-Kung Uni. Hosp.
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Taipei, Taiwan, 10048
        • National Taiwan University Hospital
    • Changhua
      • Changhua County, Changhua, Taiwan, 50006
        • Changhua Christian Hospital
    • Chiayi
      • Dalin Town, Chiayi, Taiwan, 622
        • Buddhist Dalin Tzu Chi General Hospital
    • Taoyuan County
      • Guei Shan Township, Taoyuan County, Taiwan, 333
        • Chang Gung Memorial Hospital - Linkou
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 1250
        • Baskent University Dr. Turgut Noyan Research and Training Center
      • Ankara, Turkey (Türkiye), 6200
        • Abdurrahman Yurtaslan Ankara Oncology, education and Research Hospital
      • Ankara, Turkey (Türkiye), 6230
        • Hacettepe University Faculty of Medicine
      • Antalya, Turkey (Türkiye), 7090
        • Memorial Antalya Hastanesi
      • Diyarbakır, Turkey (Türkiye), 21100
        • Dicle Üniversitesi
      • Edirne, Turkey (Türkiye), 22030
        • Trakya University
      • Istanbul, Turkey (Türkiye), 34722
        • Istanbul Medeniyet University
      • Izmir, Turkey (Türkiye), 35360
        • zmir Katip Çelebi Üniversitesi Atatürk Eitim Ve Aratrma Hastanesi
      • Izmir, Turkey (Türkiye), 9035575
        • Izmir Medical Park Hospital
      • Malatya, Turkey (Türkiye), 44280
        • İnönü Üniversitesi Turgut Özal Tıp Merkezi
      • Sarıyer, Turkey (Türkiye), 34457
        • Acıbadem Maslak Hastanesi
    • İzmir
      • Bornova, İzmir, Turkey (Türkiye), 35100
        • Ege Universitesi Hastanesi
  • Ukraine
      • Chernivtsi, Ukraine, 58013
        • Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center"
      • Kryvyi Rig, Ukraine, 50000
        • Medical Center "Mriya Med-Service", LLC
      • Kyiv, Ukraine, 03115
        • Municipal non-profit enterprise "Kyiv City Clinical Oncology Center" of executive body of Kyiv City Counci -T
      • Odesa, Ukraine, 65025
        • Municipal non-profit enterprise'Odesa Regional Clinical Hospital'of Odesa Regional Council
    • Dnipropetrovsk Oblast
      • Dnipro, Dnipropetrovsk Oblast, Ukraine, 49102
        • Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Medical University"
    • Kharkivs’ka Oblast’
      • Kharkiv, Kharkivs’ka Oblast’, Ukraine, 61070
        • CNPE "Regional Center of Oncology"
    • Odesa Oblast
      • Odesa, Odesa Oblast, Ukraine, 65055
        • Odessa Regional Oncology Center
    • Sumska Oblast
      • Sumy, Sumska Oblast, Ukraine, 40022
        • Sumy regional clinical oncological dispensary
    • Vinnytsia Oblast
      • Vinnytsia, Vinnytsia Oblast, Ukraine, 21029
        • Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council"
    • Volyn Oblast
      • Lutsk, Volyn Oblast, Ukraine, 43018
        • Municipal Enterprise "Volyn Regional Medical Oncology Centre" of the Volyn Regional Council
    • Zaporizhzhia Oblast
      • Zaporizhya, Zaporizhzhia Oblast, Ukraine, 69059
        • "Oncolife" LLC
  • United Kingdom
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
        • City Hospital, Nottingham University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed, Stage IIIB-IIIC or Stage IV non-squamous NSCLC that is not suitable for radical surgery or radiation therapy.
  • A RET gene fusion in tumor and/or blood from a qualified laboratory.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Adequate hematologic, hepatic and renal function.
  • Willingness of men and women of reproductive potential to observe conventional and highly effective birth control for the duration of treatment and for 6 months after.
  • Ability to swallow capsules.

Exclusion Criteria:

  • Additional validated oncogenic drivers in NSCLC if known.
  • Prior systemic therapy for metastatic disease. Treatment (chemotherapy, immunotherapy, or biological therapy) in the adjuvant/neoadjuvant setting is permitted if it was completed at least 6 months prior to randomization.
  • Major surgery within 3 weeks prior to planned start of selpercatinib.
  • Radiotherapy for palliation within 1 week of the first dose of study treatment or any radiotherapy within 6 months prior to the first dose of study treatment if more than 30 Gy to the lung.
  • Symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or untreated spinal cord compression.
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 milliseconds.
  • Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment.
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
  • Pregnancy or lactation.
  • Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers or a malignancy diagnosed ≥2 years previously and not currently active.
  • Uncontrolled, disease related pericardial effusion or pleural effusion.
  • Requiring chronic treatment with steroids.

Exclusion Criteria for Participants Receiving Pembrolizumab:

  • History of interstitial lung disease or interstitial pneumonitis.
  • Active autoimmune disease or any illness or treatment that could compromise the immune system.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Selpercatinib - Treatment A (TRT A)
160 milligram (mg) Selpercatinib administered orally twice daily (BID) continuously in 21-day cycles.
Drug: Selpercatinib
Administered orally
Other Names:
  • LOXO-292
  • LY3527723
Active Comparator: Pemetrexed and Platinum with or without Pembrolizumab - (TRT B)
Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 [maximum dose of 750 mg] IV), or cisplatin (75 mg/m2 cisplatin IV) on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Drug: Pembrolizumab
Administered IV
Drug: Carboplatin
Administered IV
Drug: Cisplatin
Administered IV
Drug: Pemetrexed
Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (With Pembrolizumab)
Time Frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
PFS by BICR (With or Without Pembrolizumab)
Time Frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participant With Disease Control Rate (DCR) by BICR (With Pembrolizumab)
Time Frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
DCR by BICR (with Pembrolizumab) is defined as the number of participants who achieve a BOR of complete response (CR), partial response (PR), or stable disease (SD) lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Percentage of Participant With DCR by BICR (With or Without Pembrolizumab)
Time Frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
DCR by BICR (with or without Pembrolizumab) is defined as the number of participants who achieve a BOR of CR, PR, or SD lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
PFS2 (With Pembrolizumab)
Time Frame: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.
Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
PFS2 (With or Without Pembrolizumab)
Time Frame: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.
Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR (With Pembrolizumab)
Time Frame: Baseline through Disease Progression or Death Up to 31 Months
ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.
Baseline through Disease Progression or Death Up to 31 Months
ORR: Percentage of Participants With CR or PR by BICR (With or Without Pembrolizumab)
Time Frame: Baseline through Disease Progression or Death Up to 31 Months
ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.
Baseline through Disease Progression or Death Up to 31 Months
Duration of Response (DoR) by BICR (With Pembrolizumab)
Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
DOR by BICR (With or Without Pembrolizumab)
Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
Overall Survival (OS) (With Pembrolizumab)
Time Frame: Baseline to Date of Death from Any Cause Up to 38 Months
Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data was censored on the last date the participant is known to be alive.
Baseline to Date of Death from Any Cause Up to 38 Months
OS (With or Without Pembrolizumab)
Time Frame: Baseline to Date of Death from Any Cause Up to 38 Months
Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.
Baseline to Date of Death from Any Cause Up to 38 Months
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 by BICR (With Pembrolizumab)
Time Frame: Baseline through Central Nervous System (CNS) Progression or Death up to 31 Months
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with Pembrolizumab)
Baseline through Central Nervous System (CNS) Progression or Death up to 31 Months
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)
Time Frame: Baseline through CNS Progression or Death Up to 31 Months
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab)
Baseline through CNS Progression or Death Up to 31 Months
Median Intracranial DOR Per RECIST 1.1 by BICR (With Pembrolizumab)
Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Intracranial DOR per RECIST 1.1 by BICR (with Pembrolizumab)
Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Median Intracranial DOR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)
Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Median Intracranial DOR per RECIST 1.1 by BICR (with or without Pembrolizumab)
Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Time to Deterioration of Pulmonary Symptoms (With Pembrolizumab)
Time Frame: Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months
Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-Symptom Assessment Questionnaire (SAQ) (with Pembrolizumab)
Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months
Time to Deterioration of Pulmonary Symptoms (With or Without Pembrolizumab)
Time Frame: Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months
Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-SAQ (with or without Pembrolizumab)
Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months
The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants With RET-Positive Specimens as Called by the Central Lab, Which is Also RET-Positive as Called by a Local Lab (Positive Percent Agreement)
Time Frame: Baseline
The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement)
Baseline
Median Time to CNS Progression Per RECIST 1.1 by BICR (With Pembrolizumab)
Time Frame: Baseline through CNS Progression or Death Up to 31 Months
Time to CNS Progression per RECIST 1.1 by BICR (with Pembrolizumab)
Baseline through CNS Progression or Death Up to 31 Months
Median Time to CNS Progression Per RECIST 1.1 by BICR (With or Without Pembrolizumab)
Time Frame: Baseline through CNS Progression or Death Up to 31 Months
Time to CNS Progression per RECIST 1.1 by BICR (with or without Pembrolizumab)
Baseline through CNS Progression or Death Up to 31 Months
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) by BICR (With Pembrolizumab)
Time Frame: Baseline through CNS Progression or Death Up to 31 Months
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with Pembrolizumab)
Baseline through CNS Progression or Death Up to 31 Months
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RANO-BM by BICR (With or Without Pembrolizumab)
Time Frame: Baseline through CNS Progression or Death Up to 31 Months
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with or without Pembrolizumab)
Baseline through CNS Progression or Death Up to 31 Months
Intracranial DOR Per RANO-BM by BICR (With Pembrolizumab)
Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Intracranial DOR per RANO-BM by BICR (with Pembrolizumab)
Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Intracranial DOR Per RANO-BM by BICR (With or Without Pembrolizumab)
Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Intracranial DOR per RANO-BM by BICR (with or without Pembrolizumab)
Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Collaborators

Loxo Oncology, Inc.

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 17, 2020

Primary Completion (Actual)

May 1, 2023

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

December 9, 2019

First Submitted That Met QC Criteria

December 9, 2019

First Posted (Actual)

December 11, 2019

Study Record Updates

Last Update Posted (Estimated)

October 21, 2025

Last Update Submitted That Met QC Criteria

October 17, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17479
  • J2G-MC-JZJC (Other Identifier: Eli Lilly and Company)
  • 2019-001979-36 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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