Non-Small Cell Lung CancerPhase 3LIBRETTO-431NCT04194944
A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
A Phase 3 study testing Selpercatinib, Carboplatin and Cisplatin in people with Non-Small Cell Lung Cancer, run by Eli Lilly and Company at 196 sites in 26 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Selpercatinib, Carboplatin and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 261 participants
- Where
- 196 sitesin 26 countries
- Study dates
- 17 Feb 2020to Jun 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
196 sites in 26 countries.
196 sites in 26 countries
Spain23 sites
Hospital General Universitario de Alicante
Alicante, 03010
Institut Català d'Oncologia (ICO) - Badalona
Badalona, Barcelona [Barcelona], 08916
Parc de Salut Mar - Hospital del Mar
Barcelona, 08003
Hospital Universitari Dexeus
Barcelona, 08028
Instituto Catalan de Oncologia - Hospital Duran i Reynals
Barcelona, 08908
Hospital de la Santa Creu i Sant Pau
Barcelona, 8041
Complejo Hospitalario de Jaén
Jaén, 23007
Hospital Insular de Gran Canaria
Las Palmas de Gran Canaria, Las Palmas, 35016
Clinica Universidad de Navarra
Madrid, 28027
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Hospital Regional Universitario
Málaga, 29011
Hospital Fundacion Son Llatzer
Palma de Mallorca, Balearic Islands, 07198
Clinica Universitaria De Navarra
Pamplona, Navarre, 31008
Complejo Hospitalario de Navarra
Pamplona, 31009
CHUS - Hospital Clinico Universitario
Santiago de Compostela, Galicia [Galicia], 15706
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen Del Rocio
Seville, 41013
Hospital Clínico Universitario de Valencia
Valencia, 46010
Hospital Universitari i Politecnic La Fe
Valencia, 46026
China15 sites
Beijing Cancer hospital
Beijing, Beijing Municipality, 100142
Jilin Cancer Hospital
Changchun, Jilin
Hunan Provincial People's Hospital
Changsha, Hunan, 410005
Hunan Cancer Hospital
Changsha, Hunan, 410013
Changzhou No.2 People's Hospital
Changzhou, Jiangsu
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
First affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510080
The First Affiated Hospital Of Guangzhou Medical Collage
Guangzhou, Guangzhou, 510120
Zhejiang Cancer Hospital
Hangzhou, Zhejiang
First Affiliated Hosp of College of Med, Zhejiang University
Hangzhou, 310003
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, 200433
Shanghai Chest Hospital
Shanghai, 200030
Xinjiang Medical University Cancer Hospital - Urumqi
Ürümqi, Xinjiang, 830000
Wuhan Union Hospital
Wuhan, Hubei, 430022
Taiwan14 sites
Changhua Christian Hospital
Changhua County, Changhua, 50006
Buddhist Dalin Tzu Chi General Hospital
Dalin Town, Chiayi, 622
Chang Gung Memorial Hospital - Linkou
Guei Shan Township, Taoyuan County, 333
E-Da hospital
Kaohsiung City, 82445
Chang Gung Memorial Hospital at Kaohsiung
Kaohsiung City, 83301
Tri-Service General Hospital
Neihu Taipei, 114
Taipei Medical University Shuang Ho Hospital
New Taipei City, 235
Chung Shan Medical University Hospital
Taichung, 402
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 407
National Cheng-Kung Uni. Hosp.
Tainan, 704
Chi Mei Hospital - Liouying Branch
Tainan, 73657
National Taiwan University Hospital
Taipei, 10048
Taipei Veterans General Hospital
Taipei, 11217
Italy13 sites
Azienda Ospedaliera San Giuseppe Moscati
Avellino, 83100
Cro-Irccs
Aviano, Friuli Venezia Giulia, 33081
IRCCS - AOU di Bologna
Bologna, 40138
ASST Grande Ospedale Metropolitano Niguarda
Milan, Milano, 20162
Ospedale San Gerardo-ASST Monza
Monza, Lombardy, 20900
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Naples, Campania, 80131
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
Orbassano, Torino, 10043
Azienda Ospedaliera Universitaria Pisana
Pisa, 56126
Ospedale Santa Maria delle Croci
Ravenna, Emilia-Romagna, 48121
Istituto Nazionale Tumori Regina Elena
Roma, 00144
Azienda Ospedaliera San Camillo Forlanini
Rome, Lazio, 00152
Fondazione Policlinico Universitario Agostino Gemelli
Rome, Lazio, 00168
Humanitas
Rozzano, Milano, 20089
Turkey (Türkiye)12 sites
Baskent University Dr. Turgut Noyan Research and Training Center
Adana, Turkey, 1250
Abdurrahman Yurtaslan Ankara Oncology, education and Research Hospital
Ankara, Turkey, 6200
Hacettepe University Faculty of Medicine
Ankara, 6230
Memorial Antalya Hastanesi
Antalya, 7090
Ege Universitesi Hastanesi
Bornova, İzmir, 35100
Dicle Üniversitesi
Diyarbakır, 21100
Trakya University
Edirne, 22030
Istanbul Medeniyet University
Istanbul, 34722
zmir Katip Çelebi Üniversitesi Atatürk Eitim Ve Aratrma Hastanesi
Izmir, 35360
Izmir Medical Park Hospital
Izmir, 9035575
Inonu Universitesi Turgut Ozal Tıp Merkezi
Malatya, 44280
Acıbadem Maslak Hastanesi
Sariyer, 34457
Brazil11 sites
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, São Paulo, 14784-400
Hospital de Cancer de Londrina
Londrina, Paraná, 86015-520
Hospital São Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Grupo COI - Clínicas Oncológicas Integradas
Rio de Janeiro, Rio de Janeiro, 22775-001
Instituto Nacional de Câncer - INCA
Rio de Janeiro, 20231-050
Centro de Tratamento de Tumores Botafogo para Oncoclinicas Rio de Janeiro SA
Rio de Janeiro, 22250-905
Núcleo de Oncologia da Bahia
Salvador, Estado de Bahia, 40170-070
Hospital Sírio Libanês
São Paulo, Brazil, 01308-060
Instituto D'Or de Pesquisa e Ensino (IDOR)
São Paulo, São Paulo, 04543-000
Icesp - Instituto Do Câncer Do Estado de São Paulo
São Paulo, 01246000
Hospital Sírio Libanês
São Paulo, 01308-060
Japan11 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Japanese Foundation for Cancer Research
Koto, Tokyo, 135-8550
Tominaga Hospital
Nakatogari, Shizuoka, 411-8777
Okayama University Hospital
Okayama, 700-8558
Osaka International Cancer Institute
Osaka, 541-8567
Kindai University Hospital- Osakasayama Campus
Osaka Sayama-shi, Osaka, 589 8511
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804
Kanagawa cancer center
Yokohama, Kanagawa, 241-8515
Tottori University Hospital
Yonago, Tottori, 683-8504
Ukraine11 sites
Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center"
Chernivtsi, 58013
Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Medical University"
Dnipro, Dnipropetrovsk Oblast, 49102
CNPE "Regional Center of Oncology"
Kharkiv, Kharkiv Oblast, 61070
Medical Center "Mriya Med-Service", LLC
Kryvyi Rig, 50000
Municipal non-profit enterprise "Kyiv City Clinical Oncology Center" of executive body of Kyiv City Counci -T
Kyiv, 03115
Municipal Enterprise "Volyn Regional Medical Oncology Centre" of the Volyn Regional Council
Lutsk, Volyn Oblast, 43018
Odessa Regional Oncology Center
Odesa, Odesa Oblast, 65055
Municipal non-profit enterprise'Odesa Regional Clinical Hospital'of Odesa Regional Council
Odesa, 65025
Sumy regional clinical oncological dispensary
Sumy, Sumska Oblast, 40022
Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council"
Vinnytsia, Vinnytsia Oblast, 21029
"Oncolife" LLC
Zaporizhya, Zaporizhzhia Oblast, 69059
Russia10 sites
Arkhangelsk Clinical Oncological Dispensary
Arkhangelsk, 163045
Kaluga Regional Clinical Oncology Center
Kaluga, Kalužskaja Oblast, 248007
Republican Clinical Oncology Dispensary
Kazan', 420029
First Moscow State Medical University I.M. Sechenov
Moscow, 119991
Hadassah Medical
Moscow, 121205
Murmansk Regional Clinical Hospital P.A. Bayandina
Murmansk, Murmansk Oblast, 183047
Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (oncological) named afte -T
Saint Petersburg, Sankt-Peterburg, 197758
Scientific research institution of oncology named after N.N. Petrov
Saint Petersburg, Sankt-Peterburg, 197758
Samara Regional Clinical Oncology Center
Samara, Samara Oblast, 443031
GBUZ Republican Clinical Oncological Dispensary
Ufa, Baškortostan, Respublika, 450054
South Korea9 sites
Konyang University Hospital
Daejeon, 35365
Boramae Medical Center
Dongjak-gu, Seoul-teukbyeolsi [Seoul], 07061
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Gachon University Gil Medical Center
Incheon, Korea, 21565
Gyeongsang National University Hospital
Jinju, Kyǒngsangnam-do, 52727
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Asan Medical Center
Seoul, Korea, 05505
Seoul National University Hospital
Seoul, Seoul, Korea, 03080
Samsung Medical Center
Seoul, 06351
Germany8 sites
Charite Universitätsmedizin Berlin Campus Benjamin Franklin
Berlin, 12203
University Hospital of Cologne
Cologne, North Rhine-Westphalia, 50937
Asklepios Fachkliniken München-Gauting
Gauting, Bavaria, 82131
Franziskus-Hospital Harderberg
Georgsmarienhütte, Lower Saxony, 49124
Universitätsmedizin Göttingen
Göttingen, Lower Saxony, 37075
LungenClinic Grosshansdorf
Großhansdorf, Schleswig-Holstein, 22927
Thoraxklinik-Heidelberg gGmbH
Heidelberg, Baden-Wurttemberg, 69126
Klinikverbund Kempten-Oberallgäu
Immenstadt im Allgäu, Bavaria, 87509
Australia7 sites
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Monash Health
Clayton, Victoria, 3168
Peninsula Oncology Centre
Frankston, 3199
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
St Vincent's Hospital
Melbourne, Victoria, 3065
Calvary Mater Newcastle
Waratah, New South Wales, 2298
Westmead Hospital
Westmead, New South Wales, 2145
Belgium7 sites
UZ Brussel
Brussels, Bruxelles-Capitale, Région de, 1090
UZ Gent Hospital
Ghent, 9000
UZ Leuven
Leuven, Vlaams-Brabant, 3000
AZ Sint-Maarten, Campus Leopoldstraat 2
Mechelen, 2800
CHU UCL Namur/Site Sainte Elisabeth
Namur, 5000
AZ Delta
Roeselare, West Flanders, 8800
AZ Nikolaas
Sint-Niklaas, Oost-Vlaanderen, B-9100
Romania7 sites
Gral Medical Diagnostic Center
Bucharest, Bucharest, 031422
Institutul Oncologic
Bucharest, Bucharest, 22328
Spitalul Universitar de Urgență București
Bucharest, 050098
Institutul Oncologic
Cluj-Napoca, 400015
Constanta County Emergency Clinical Hospital Sf.Ap.Andrei
Constanța, Constanța County, 900591
Spitalul Județean Sfântul Ioan cel Nou Suceava
Suceava, 720237
Cabinet Medical Oncomed
Timișoara, Timiș County, 300239
France6 sites
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
Clermont-Ferrand, Puy-de-Dôme, 63011
Chu Grenoble Alpes
La Tronche, Isère, 38700
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69373
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
Marseille, Bouches-du-Rhône, 13385
Institut Régional du Cancer Montpellier
Montpellier, Hérault, 34298
Hopitaux Universitaires Paris Centre-Hopital Cochin
Paris, 75014
Argentina5 sites
Centro de Oncología e Investigación de Buenos Aires
Berazategui, Buenos Aires, B1884BBF
Fundacion CENIT para la Investigacion en Neurociencias
Caba, Buenos Aires, 1125
Alexander Fleming
Ciudad de Buenos Aires, C1426ANZ
Clínica El Castaño
San Juan, 5400
Clinica Viedma
Viedma, Río Negro Province, R8500ACE
Israel5 sites
Soroka Medical Center
Beersheba, 8400000
Rambam Health Care Campus
Haifa, Ḥeifā, 3109601
Shaare Zedek Medical Center
Jerusalem, 9103102
Hadassah Medical Center
Jerusalem, 9112001
Sheba Medical Center
Ramat Gan, 5262100
Greece4 sites
Sotiria Thoracic Diseases Hospital of Athens
Athens, Attikí, 115 27
University General Hospital of Heraklion
Heraklion, Krítí, 711 10
European Interbalkan Medical Center
Thessaloniki, Thessaloníki, 570 01
G. Papanikolaou General Hospital
Thessaloniki, Thessaloníki, 570 10
Netherlands4 sites
Jeroen Bosch Hospital
's-Hertogenbosch, North Brabant, 5223 GZ
Amsterdam UMC, locatie VUmc
Amsterdam, 1081 HV
Ziekenhuis St. Jansdal
Harderwijk, Gelderland, 3844 DG
Erasmus Medisch Centrum
Rotterdam, South Holland, 3015 CE
Czechia3 sites
Fakultni nemocnice Olomouc
Olomouc, 779 00
Nemocnice AGEL Ostrava - Vitkovice a.s.
Ostrava - Vitkovice, 70384
Fakultni nemocnice Bulovka
Prague, 180 81
Mexico3 sites
Actualidad Basada en la Investigación del Cáncer
Guadalajara, Jalisco, 44680
Health Pharma Professional Research S.A. de C.V:
Mexico City, Federal District, 03100
Oncologico Potosino, S.C.
San Luis Potosí City, 78209
Canada2 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Hong Kong2 sites
Hong Kong United Oncology Centre
Jordan, Kowloon, 999077
Prince of Wales Hospital
Shatin, 852
Poland2 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw, 02-781
United Kingdom1 site
City Hospital, Nottingham University Hospitals
Nottingham, Nottinghamshire, NG5 1PB
About this study
Official title: 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Selpercatinib, Carboplatin, Cisplatin, Pemetrexed, Pembrolizumab
- Keywords
- targeted therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelpercatinibDrug
Also called LY3527723, LOXO-292
Administered orally
CarboplatinDrug
Administered IV
CisplatinDrug
Administered IV
PemetrexedDrug
Administered IV
PembrolizumabDrug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| Selpercatinib - Treatment A (TRT A) | Experimental | 160 milligram (mg) Selpercatinib administered orally twice daily (BID) continuously in 21-day cycles. Receives: Drug: Selpercatinib |
| Pemetrexed and Platinum with or without Pembrolizumab - (TRT B) | Active comparator | 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. Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (With Pembrolizumab)
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.
Measured: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
PFS by BICR (With or Without Pembrolizumab)
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.
Measured: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Secondary outcomes (23)
Percentage of Participant With Disease Control Rate (DCR) by BICR (With Pembrolizumab)
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.
Measured: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Percentage of Participant With DCR by BICR (With or Without Pembrolizumab)
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.
Measured: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
PFS2 (With Pembrolizumab)
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.
Measured: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
PFS2 (With or Without Pembrolizumab)
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.
Measured: 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)
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.
Measured: Baseline through Disease Progression or Death Up to 31 Months
ORR: Percentage of Participants With CR or PR by BICR (With or Without Pembrolizumab)
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.
Measured: Baseline through Disease Progression or Death Up to 31 Months
Duration of Response (DoR) by BICR (With Pembrolizumab)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Baseline to Date of Death from Any Cause Up to 38 Months
OS (With or Without Pembrolizumab)
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.
Measured: 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)
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with Pembrolizumab)
Measured: 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)
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab)
Measured: Baseline through CNS Progression or Death Up to 31 Months
Median Intracranial DOR Per RECIST 1.1 by BICR (With Pembrolizumab)
Intracranial DOR per RECIST 1.1 by BICR (with Pembrolizumab)
Measured: 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)
Median Intracranial DOR per RECIST 1.1 by BICR (with or without Pembrolizumab)
Measured: 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 to Deterioration of Pulmonary Symptoms Measured by the NSCLC-Symptom Assessment Questionnaire (SAQ) (with Pembrolizumab)
Measured: Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months
Time to Deterioration of Pulmonary Symptoms (With or Without Pembrolizumab)
Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-SAQ (with or without Pembrolizumab)
Measured: 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)
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)
Measured: Baseline
Median Time to CNS Progression Per RECIST 1.1 by BICR (With Pembrolizumab)
Time to CNS Progression per RECIST 1.1 by BICR (with Pembrolizumab)
Measured: 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 to CNS Progression per RECIST 1.1 by BICR (with or without Pembrolizumab)
Measured: 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)
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with Pembrolizumab)
Measured: 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)
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with or without Pembrolizumab)
Measured: Baseline through CNS Progression or Death Up to 31 Months
Intracranial DOR Per RANO-BM by BICR (With Pembrolizumab)
Intracranial DOR per RANO-BM by BICR (with Pembrolizumab)
Measured: 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)
Intracranial DOR per RANO-BM by BICR (with or without Pembrolizumab)
Measured: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2019
- Study start17 Feb 2020
- Primary completion1 May 2023
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 261 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Loxo Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04194944
- Sponsor's protocol ID
- 17479
- Other IDs
- J2G-MC-JZJC, 2019-001979-36, 2019
- Acronym
- LIBRETTO-431
- Status last verified
- Oct 2026
- First submitted
- 9 Dec 2019
- Last updated
- 21 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Duke ES, Bradford D, Sinha AK, Li X, Mishra-Kalyani PS, de Claro RA, Larkins E, Drezner N. Selpercatinib and the Crossover Conundrum: Potential Impact of Postprogression Therapies on Overall Survival. J Clin Oncol. 2026 May 20;44(15):1457-1464. doi: 10.1200/JCO-25-02375. Epub 2026 Apr 17.
PubMed 41996652Perol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. doi: 10.1200/JCO.24.00724. Epub 2024 Jun 3.
PubMed 38828957Zhou C, Solomon B, Loong HH, Park K, Perol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. doi: 10.1056/NEJMoa2309457. Epub 2023 Oct 21.
PubMed 37870973Claerhout S, Lehnert S, Vander Borght S, Spans L, Dooms C, Wauters E, Vansteenkiste J, Weynand B, Deraedt K, Bourgain C, Vanden Bempt I. Targeted RNA sequencing for upfront analysis of actionable driver alterations in non-small cell lung cancer. Lung Cancer. 2022 Apr;166:242-249. doi: 10.1016/j.lungcan.2022.02.013. Epub 2022 Mar 1.
PubMed 35378489Solomon BJ, Zhou CC, Drilon A, Park K, Wolf J, Elamin Y, Davis HM, Soldatenkova V, Sashegyi A, Lin AB, Lin BK, F Loong HH, Novello S, Arriola E, Perol M, Goto K, Santini FC. Phase III study of selpercatinib versus chemotherapy +/- pembrolizumab in untreated RET positive non-small-cell lung cancer. Future Oncol. 2021 Mar;17(7):763-773. doi: 10.2217/fon-2020-0935. Epub 2020 Nov 5.
PubMed 33150799