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

Non-Small Cell Lung Cancer Clinical Trial

— LIBRETTO-431  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04194944
• Other study ID #: 17479
• Secondary ID: J2G-MC-JZJC2019-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 17, 2020
• Est. completion date: June 18, 2026

Study information

• Verified date: June 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 261
• Est. completion date: June 18, 2026
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Selpercatinib
Administered orally
• Carboplatin
Administered IV
• Cisplatin
Administered IV
• Pemetrexed
Administered IV
• Pembrolizumab
Administered IV

Locations

Country	Name	City	State
Argentina	Centro de Oncología e Investigación de Buenos Aires	Berazategui	Buenos Aires
Argentina	Fundacion CENIT para la Investigacion en Neurociencias	Caba	Buenos Aires
Argentina	Alexander Fleming	Ciudad de Buenos Aires
Argentina	Clínica El Castaño	San Juan
Argentina	Clinica Viedma	Viedma	Río Negro
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Monash Health	Clayton	Victoria
Australia	Peninsula Oncology Centre	Frankston
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	St Vincent's Hospital	Melbourne	Victoria
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	UZ Brussel	Brussels	Bruxelles-Capitale, Région De
Belgium	UZ Gent Hospital	Gent
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
Belgium	AZ Sint-Maarten, Campus Leopoldstraat 2	Mechelen
Belgium	CHU UCL Namur/Site Sainte Elisabeth	Namur
Belgium	AZ Delta	Roeselare	West Flanders
Belgium	AZ Nikolaas	Sint Niklaas	Oost-Vlaanderen
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	Sao Paulo
Brazil	Hospital de Cancer de Londrina	Londrina	Paraná
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul
Brazil	Centro de Tratamento de Tumores Botafogo para Oncoclinicas Rio de Janeiro SA	Rio de Janeiro
Brazil	Grupo COI - Clínicas Oncológicas Integradas	Rio de Janeiro	RJ
Brazil	Instituto Nacional de Câncer - INCA	Rio de Janeiro
Brazil	Núcleo de Oncologia da Bahia	Salvador	Bahia
Brazil	Hospital Sírio Libanês	Sao Paolo
Brazil	Icesp - Instituto Do Câncer Do Estado de São Paulo	Sao Paulo
Brazil	Instituto D'Or de Pesquisa e Ensino (IDOR)	Sao Paulo	SP
Brazil	Hospital Sírio Libanês	São Paulo
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
China	Beijing Cancer hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	Changzhou No.2 People's Hospital	Changzhou	Jiangsu
China	West China Hospital of Sichuan University	Cheng Du	Sichuan
China	First affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The First Affiated Hospital Of Guangzhou Medical Collage	Guangzhou	Guangzhou
China	First Affiliated Hosp of College of Med, Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Shanghai Chest Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	Xinjiang Medical University Cancer Hospital - Urumqi	Urumqi	Xinjiang
China	Wuhan Union Hospital	Wuhan	Hubei
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Nemocnice AGEL Ostrava - Vitkovice a.s.	Ostrava - Vitkovice
Czechia	Fakultni nemocnice Bulovka	Praha 8
France	Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne	Clermont-Ferrand	Puy-de-Dôme
France	Chu Grenoble Alpes	La Tronche	Isère
France	Centre Leon Berard	Lyon	Rhône-Alpes
France	Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone	Marseille	Bouches-du-Rhône
France	Institut Régional du Cancer Montpellier	Montpellier Cedex 5	Hérault
France	Hopitaux Universitaires Paris Centre-Hopital Cochin	Paris
Germany	Charite Universitätsmedizin Berlin Campus Benjamin Franklin	Berlin
Germany	Asklepios Fachkliniken München-Gauting	Gauting	Bayern
Germany	Franziskus-Hospital Harderberg	Georgsmarienhütte	Niedersachsen
Germany	Universitätsmedizin Göttingen	Göttingen	Niedersachsen
Germany	LungenClinic Grosshansdorf	Grosshansdorf	Schleswig-Holstein
Germany	Thoraxklinik-Heidelberg gGmbH	Heidelberg	Baden-Württemberg
Germany	Klinikverbund Kempten-Oberallgäu	Immenstadt	Bayern
Germany	University Hospital of Cologne	Köln	Nordrhein-Westfalen
Greece	Sotiria Thoracic Diseases Hospital of Athens	Athens	Attikí
Greece	University General Hospital of Heraklion	Heraklion	Krítí
Greece	European Interbalkan Medical Center	Thessaloniki	Thessaloníki
Greece	G. Papanikolaou General Hospital	Thessaloniki	Thessaloníki
Hong Kong	Hong Kong United Oncology Centre	Jordan	Kowloon
Hong Kong	Prince of Wales Hospital	Shatin
Israel	Soroka Medical Center	Beer-Sheva
Israel	Rambam Health Care Campus	Haifa	?eifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino
Italy	Cro-Irccs	Aviano	Friuli-Venezia Giulia
Italy	IRCCS - AOU di Bologna	Bologna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan	Milano
Italy	Ospedale San Gerardo-ASST Monza	Monza	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli	Campania
Italy	Azienda Sanitaria Ospedaliera S Luigi Gonzaga	Orbassano	Torino
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Ospedale Santa Maria delle Croci	Ravenna	Emilia-Romagna
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma	Lazio
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Italy	Humanitas	Rozzano	Milano
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Japanese Foundation for Cancer Research	Koto	Tokyo
Japan	Tominaga Hospital	Nagaizumi	Shizuoka
Japan	Okayama University Hospital	Okayama
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital- Osakasayama Campus	Osaka Sayama-shi	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Kanagawa cancer center	Yokohama	Kanagawa
Japan	Tottori University Hospital	Yonago	Tottori
Korea, Republic of	Konyang University Hospital	Daejon
Korea, Republic of	Boramae Medical Center	Dongjak-gu	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Korea
Korea, Republic of	Gyeongsang National University Hospital	Jin-ju-si	Kyongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Korea
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul, Korea
Mexico	Actualidad Basada en la Investigación del Cáncer	Guadalajara	Jalisco
Mexico	Health Pharma Professional Research S.A. de C.V:	Mexico City	Federal District
Mexico	Oncologico Potosino, S.C.	San Luis Potosí
Netherlands	Amsterdam UMC, locatie VUmc	Amsterdam
Netherlands	Jeroen Bosch ziekenhuis	Den Bosch	Noord-Brabant
Netherlands	Ziekenhuis St. Jansdal	Harderwijk	Gelderland
Netherlands	Erasmus Medisch Centrum	Rotterdam	Zuid-Holland
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warszawa
Romania	Institutul Oncologic	Bucharest	Bucure?ti
Romania	Gral Medical Diagnostic Center	Bucuresti	Bucure?ti
Romania	Spitalul Universitar de Urgen?a Bucure?ti	Bucuresti
Romania	Institutul Oncologic	Cluj-Napoca
Romania	Constanta County Emergency Clinical Hospital Sf.Ap.Andrei	Constanta	Constan?a
Romania	Spitalul Jude?ean Sfântul Ioan cel Nou Suceava	Suceava
Romania	Cabinet Medical Oncomed	Timi?oara	Timi?
Russian Federation	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk
Russian Federation	Kaluga Regional Clinical Oncology Center	Kaluga	Kalužskaja Oblast
Russian Federation	Republican Clinical Oncology Dispensary	Kazan
Russian Federation	First Moscow State Medical University I.M. Sechenov	Moscow
Russian Federation	Hadassah Medical	Moscow
Russian Federation	Murmansk Regional Clinical Hospital P.A. Bayandina	Murmansk	Murmanskaya Oblast'
Russian Federation	Scientific research institution of oncology named after N.N. Petrov	Saint Petersburg	Sankt-Peterburg
Russian Federation	Samara Regional Clinical Oncology Center	Samara	Samarskaya Oblast'
Russian Federation	Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (oncological) named afte -T	St. Petersburg	Sankt-Peterburg
Russian Federation	GBUZ Republican Clinical Oncological Dispensary	Ufa	Baškortostan, Respublika
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Institut Català d'Oncologia (ICO) - Badalona	Badalona	Barcelona [Barcelona]
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Dexeus	Barcelona
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals	Barcelona
Spain	Parc de Salut Mar - Hospital del Mar	Barcelona
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital Insular de Gran Canaria	Las palmas de gran canaria	Las Palmas
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Regional Universitario	Malaga
Spain	Hospital Fundacion Son Llatzer	Palma de Mallorca	Baleares
Spain	Clinica Universitaria De Navarra	Pamplona	Navarra
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	Galicia [Galicia]
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Taiwan	Changhua Christian Hospital	Changhua County	Changhua
Taiwan	Buddhist Dalin Tzu Chi General Hospital	Dalin Town	Chiayi
Taiwan	Chang Gung Memorial Hospital - Linkou	Guei Shan Township	Taoyuan County
Taiwan	Chang Gung Memorial Hospital at Kaohsiung	Kaohsiung
Taiwan	E-Da hospital	Kaohsiung
Taiwan	Tri-Service General Hospital	Neihu Taipei
Taiwan	Taipei Medical University Shuang Ho Hospital	New Taipei
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng-Kung Uni. Hosp.	Tainan
Taiwan	Chi Mei Hospital - Liouying Branch	Tainan City
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei City
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center	Adana
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Hacettepe University Faculty of Medicine	Ankara
Turkey	Memorial Antalya Hastanesi	Antalya
Turkey	Ege Universitesi Hastanesi	Bornova	Izmir
Turkey	Dicle Üniversitesi	Diyarbakir
Turkey	Trakya University	Edirne
Turkey	Istanbul Medeniyet University	Istanbul
Turkey	Izmir Medical Park Hospital	Izmir
Turkey	zmir Katip Çelebi Üniversitesi Atatürk Eitim Ve Aratrma Hastanesi	Izmir
Turkey	Inonu Universitesi Turgut Ozal Tip Merkezi	Malatya
Turkey	Acibadem Maslak Hastanesi	Sariyer
Ukraine	Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center"	Chernivtsi
Ukraine	Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Medical University"	Dnipro	Dnipropetrovska Oblast
Ukraine	CNPE "Regional Center of Oncology"	Kharkiv	Kharkivska Oblast
Ukraine	Medical Center "Mriya Med-Service", LLC	Kryvyi Rig
Ukraine	Municipal non-profit enterprise "Kyiv City Clinical Oncology Center" of executive body of Kyiv City Counci -T	Kyiv
Ukraine	Municipal Enterprise "Volyn Regional Medical Oncology Centre" of the Volyn Regional Council	Lutsk	Volynska Oblast
Ukraine	Municipal non-profit enterprise'Odesa Regional Clinical Hospital'of Odesa Regional Council	Odesa
Ukraine	Odessa Regional Oncology Center	Odesa	Odeska Oblast
Ukraine	Sumy regional clinical oncological dispensary	Sumy	Sumska Oblast
Ukraine	Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council"	Vinnytsia	Vinnytska Oblast
Ukraine	"Oncolife" LLC	Zaporizhya	Zaporizka Oblast
United Kingdom	City Hospital, Nottingham University Hospitals	Nottingham	Nottinghamshire

Sponsors (2)

Lead Sponsor	Collaborator
Loxo Oncology, Inc.	Eli Lilly and Company

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Primary	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.	Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Secondary	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.	Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Secondary	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.	Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
Secondary	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.	Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
Secondary	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.	Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
Secondary	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.	Baseline through Disease Progression or Death Up to 31 Months
Secondary	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.	Baseline through Disease Progression or Death Up to 31 Months
Secondary	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.	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
Secondary	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.	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
Secondary	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.	Baseline to Date of Death from Any Cause Up to 38 Months
Secondary	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.	Baseline to Date of Death from Any Cause Up to 38 Months
Secondary	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)	Baseline through Central Nervous System (CNS) Progression or Death up to 31 Months
Secondary	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)	Baseline through CNS Progression or Death Up to 31 Months
Secondary	Median Intracranial DOR Per RECIST 1.1 by BICR (With Pembrolizumab)	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
Secondary	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)	Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months
Secondary	Time to Deterioration of Pulmonary Symptoms (With Pembrolizumab)	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
Secondary	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)	Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months
Secondary	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)	Baseline
Secondary	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)	Baseline through CNS Progression or Death Up to 31 Months
Secondary	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)	Baseline through CNS Progression or Death Up to 31 Months
Secondary	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)	Baseline through CNS Progression or Death Up to 31 Months
Secondary	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)	Baseline through CNS Progression or Death Up to 31 Months
Secondary	Intracranial DOR Per RANO-BM by BICR (With Pembrolizumab)	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
Secondary	Intracranial DOR Per RANO-BM by BICR (With or Without Pembrolizumab)	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

External Links

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