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

NCT ID: NCT04194944

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 261 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-17
• Study Completion Date: 2030-06-30

Brief 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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selpercatinib - Treatment A (TRT A)

160 milligram (mg) Selpercatinib administered orally twice daily (BID) continuously in 21-day cycles.

Group Type: EXPERIMENTAL

Selpercatinib

Intervention Type: DRUG

Administered orally

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.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Administered IV

Cisplatin

Intervention Type: DRUG

Administered IV

Pemetrexed

Intervention Type: DRUG

Administered IV

Pembrolizumab

Intervention Type: DRUG

Administered IV

Interventions

Selpercatinib

Administered orally

Intervention Type: DRUG

Carboplatin

Administered IV

Intervention Type: DRUG

Cisplatin

Administered IV

Intervention Type: DRUG

Pemetrexed

Administered IV

Intervention Type: DRUG

Pembrolizumab

Administered IV

Intervention Type: DRUG

Other Intervention Names

LY3527723; LOXO-292

Eligibility Criteria

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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Loxo Oncology, Inc.

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal 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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Centro de Oncología e Investigación de Buenos Aires

Berazategui, Buenos Aires, Argentina

Fundacion CENIT para la Investigacion en Neurociencias

Caba, Buenos Aires, Argentina

Clinica Viedma

Viedma, Río Negro Province, Argentina

Alexander Fleming

Ciudad de Buenos Aires, , Argentina

Clínica El Castaño

San Juan, , Argentina

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Monash Health

Clayton, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

St Vincent's Hospital

Melbourne, Victoria, Australia

Peninsula Oncology Centre

Frankston, , Australia

UZ Brussel

Brussels, Bruxelles-Capitale, Région de, Belgium

AZ Nikolaas

Sint-Niklaas, Oost-Vlaanderen, Belgium

UZ Leuven

Leuven, Vlaams-Brabant, Belgium

AZ Delta

Roeselare, West Flanders, Belgium

UZ Gent Hospital

Ghent, , Belgium

AZ Sint-Maarten, Campus Leopoldstraat 2

Mechelen, , Belgium

CHU UCL Namur/Site Sainte Elisabeth

Namur, , Belgium

Hospital Sírio Libanês

São Paulo, Brazil, Brazil

Núcleo de Oncologia da Bahia

Salvador, Estado de Bahia, Brazil

Hospital de Cancer de Londrina

Londrina, Paraná, Brazil

Grupo COI - Clínicas Oncológicas Integradas

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Fundação Pio XII - Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

Instituto D'Or de Pesquisa e Ensino (IDOR)

São Paulo, São Paulo, Brazil

Instituto Nacional de Câncer - INCA

Rio de Janeiro, , Brazil

Centro de Tratamento de Tumores Botafogo para Oncoclinicas Rio de Janeiro SA

Rio de Janeiro, , Brazil

Icesp - Instituto Do Câncer Do Estado de São Paulo

São Paulo, , Brazil

Hospital Sírio Libanês

São Paulo, , Brazil

Cross Cancer Institute

Edmonton, Alberta, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Beijing Cancer hospital

Beijing, Beijing Municipality, China

First affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

The First Affiated Hospital Of Guangzhou Medical Collage

Guangzhou, Guangzhou, China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Wuhan Union Hospital

Wuhan, Hubei, China

Hunan Provincial People's Hospital

Changsha, Hunan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Changzhou No.2 People's Hospital

Changzhou, Jiangsu, China

Jilin Cancer Hospital

Changchun, Jilin, China

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Xinjiang Medical University Cancer Hospital - Urumqi

Ürümqi, Xinjiang, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

First Affiliated Hosp of College of Med, Zhejiang University

Hangzhou, , China

Shanghai Chest Hospital

Shanghai, , China

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Nemocnice AGEL Ostrava - Vitkovice a.s.

Ostrava - Vitkovice, , Czechia

Fakultni nemocnice Bulovka

Prague, , Czechia

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone

Marseille, Bouches-du-Rhône, France

Institut Régional du Cancer Montpellier

Montpellier, Hérault, France

Chu Grenoble Alpes

La Tronche, Isère, France

Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne

Clermont-Ferrand, Puy-de-Dôme, France

Hopitaux Universitaires Paris Centre-Hopital Cochin

Paris, , France

Thoraxklinik-Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, Germany

Asklepios Fachkliniken München-Gauting

Gauting, Bavaria, Germany

Klinikverbund Kempten-Oberallgäu

Immenstadt im Allgäu, Bavaria, Germany

Franziskus-Hospital Harderberg

Georgsmarienhütte, Lower Saxony, Germany

Universitätsmedizin Göttingen

Göttingen, Lower Saxony, Germany

University Hospital of Cologne

Cologne, North Rhine-Westphalia, Germany

LungenClinic Grosshansdorf

Großhansdorf, Schleswig-Holstein, Germany

Charite Universitätsmedizin Berlin Campus Benjamin Franklin

Berlin, , Germany

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, Greece

Hong Kong United Oncology Centre

Jordan, Kowloon, Hong Kong

Prince of Wales Hospital

Shatin, , Hong Kong

Soroka Medical Center

Beersheba, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Rambam Health Care Campus

Haifa, Ḥeifā, Israel

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, Campania, Italy

Ospedale Santa Maria delle Croci

Ravenna, Emilia-Romagna, Italy

Cro-Irccs

Aviano, Friuli Venezia Giulia, Italy

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, Italy

Fondazione Policlinico Universitario Agostino Gemelli

Rome, Lazio, Italy

Ospedale San Gerardo-ASST Monza

Monza, Lombardy, Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, Milano, Italy

Humanitas

Rozzano, Milano, Italy

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Torino, Italy

Azienda Ospedaliera San Giuseppe Moscati

Avellino, , Italy

IRCCS - AOU di Bologna

Bologna, , Italy

Azienda Ospedaliera Universitaria Pisana

Pisa, , Italy

Istituto Nazionale Tumori Regina Elena

Roma, , Italy

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Kanagawa cancer center

Yokohama, Kanagawa, Japan

Kindai University Hospital- Osakasayama Campus

Osaka Sayama-shi, Osaka, Japan

Tominaga Hospital

Nakatogari, Shizuoka, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Japanese Foundation for Cancer Research

Koto, Tokyo, Japan

Tottori University Hospital

Yonago, Tottori, Japan

Okayama University Hospital

Okayama, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Health Pharma Professional Research S.A. de C.V:

Mexico City, Federal District, Mexico

Actualidad Basada en la Investigación del Cáncer

Guadalajara, Jalisco, Mexico

Oncologico Potosino, S.C.

San Luis Potosí City, , Mexico

Ziekenhuis St. Jansdal

Harderwijk, Gelderland, Netherlands

Jeroen Bosch Hospital

's-Hertogenbosch, North Brabant, Netherlands

Erasmus Medisch Centrum

Rotterdam, South Holland, Netherlands

Amsterdam UMC, locatie VUmc

Amsterdam, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

Gral Medical Diagnostic Center

Bucharest, București, Romania

Institutul Oncologic

Bucharest, București, Romania

Constanta County Emergency Clinical Hospital Sf.Ap.Andrei

Constanța, Constanța County, Romania

Cabinet Medical Oncomed

Timișoara, Timiș County, Romania

Spitalul Universitar de Urgență București

Bucharest, , Romania

Institutul Oncologic

Cluj-Napoca, , Romania

Spitalul Județean Sfântul Ioan cel Nou Suceava

Suceava, , Romania

GBUZ Republican Clinical Oncological Dispensary

Ufa, Baškortostan, Respublika, Russia

Kaluga Regional Clinical Oncology Center

Kaluga, Kalužskaja Oblast, Russia

Murmansk Regional Clinical Hospital P.A. Bayandina

Murmansk, Murmansk Oblast, Russia

Samara Regional Clinical Oncology Center

Samara, Samara Oblast, Russia

Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (oncological) named afte -T

Saint Petersburg, Sankt-Peterburg, Russia

Scientific research institution of oncology named after N.N. Petrov

Saint Petersburg, Sankt-Peterburg, Russia

Arkhangelsk Clinical Oncological Dispensary

Arkhangelsk, , Russia

Republican Clinical Oncology Dispensary

Kazan', , Russia

First Moscow State Medical University I.M. Sechenov

Moscow, , Russia

Hadassah Medical

Moscow, , Russia

Tan Tock Seng Hospital

Singapore, , Singapore

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Gachon University Gil Medical Center

Incheon, Korea, South Korea

Asan Medical Center

Seoul, Korea, South Korea

Gyeongsang National University Hospital

Jinju, Kyǒngsangnam-do, South Korea

Seoul National University Hospital

Seoul, Seoul, Korea, South Korea

Boramae Medical Center

Dongjak-gu, Seoul-teukbyeolsi [Seoul], South Korea

Konyang University Hospital

Daejeon, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Fundacion Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

Institut Català d'Oncologia (ICO) - Badalona

Badalona, Barcelona [Barcelona], Spain

CHUS - Hospital Clinico Universitario

Santiago de Compostela, Galicia [Galicia], Spain

Hospital Insular de Gran Canaria

Las Palmas de Gran Canaria, Las Palmas, Spain

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Clinica Universitaria De Navarra

Pamplona, Navarre, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Parc de Salut Mar - Hospital del Mar

Barcelona, , Spain

Hospital Universitari Dexeus

Barcelona, , Spain

Instituto Catalan de Oncologia - Hospital Duran i Reynals

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

Clinica Universidad de Navarra

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Regional Universitario

Málaga, , Spain

Complejo Hospitalario de Navarra

Pamplona, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

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

E-Da hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital at Kaohsiung

Kaohsiung City, , Taiwan

Tri-Service General Hospital

Neihu Taipei, , Taiwan

Taipei Medical University Shuang Ho Hospital

New Taipei City, , Taiwan

Chung Shan Medical University Hospital

Taichung, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng-Kung Uni. Hosp.

Tainan City, , Taiwan

Chi Mei Hospital - Liouying Branch

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Ege Universitesi Hastanesi

Bornova, İzmir, Turkey (Türkiye)

Baskent University Dr. Turgut Noyan Research and Training Center

Adana, , Turkey (Türkiye)

Abdurrahman Yurtaslan Ankara Oncology, education and Research Hospital

Ankara, , Turkey (Türkiye)

Hacettepe University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Memorial Antalya Hastanesi

Antalya, , Turkey (Türkiye)

Dicle Üniversitesi

Diyarbakır, , Turkey (Türkiye)

Trakya University

Edirne, , Turkey (Türkiye)

Istanbul Medeniyet University

Istanbul, , Turkey (Türkiye)

zmir Katip Çelebi Üniversitesi Atatürk Eitim Ve Aratrma Hastanesi

Izmir, , Turkey (Türkiye)

Izmir Medical Park Hospital

Izmir, , Turkey (Türkiye)

Inonu Universitesi Turgut Ozal Tıp Merkezi

Malatya, , Turkey (Türkiye)

Acıbadem Maslak Hastanesi

Sarıyer, , Turkey (Türkiye)

Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Medical University"

Dnipro, Dnipropetrovsk Oblast, Ukraine

CNPE "Regional Center of Oncology"

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Odessa Regional Oncology Center

Odesa, Odesa Oblast, Ukraine

Sumy regional clinical oncological dispensary

Sumy, Sumska Oblast, Ukraine

Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council"

Vinnytsia, Vinnytsia Oblast, Ukraine

Municipal Enterprise "Volyn Regional Medical Oncology Centre" of the Volyn Regional Council

Lutsk, Volyn Oblast, Ukraine

"Oncolife" LLC

Zaporizhya, Zaporizhzhia Oblast, Ukraine

Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center"

Chernivtsi, , 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 non-profit enterprise'Odesa Regional Clinical Hospital'of Odesa Regional Council

Odesa, , Ukraine

City Hospital, Nottingham University Hospitals

Nottingham, Nottinghamshire, United Kingdom

Countries

Argentina; Australia; Belgium; Brazil; Canada; China; Czechia; France; Germany; Greece; Hong Kong; Israel; Italy; Japan; Mexico; Netherlands; Poland; Romania; Russia; Singapore; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Perol 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.

Reference Type: DERIVED

PMID: 38828957 (View on PubMed)

Zhou 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.

Reference Type: DERIVED

PMID: 37870973 (View on PubMed)

Claerhout 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.

Reference Type: DERIVED

PMID: 35378489 (View on PubMed)

Solomon 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.

Reference Type: DERIVED

PMID: 33150799 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lilly.com/en-US/trial/230195

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

Other Identifiers

J2G-MC-JZJC

Identifier Type: OTHER

Identifier Source: secondary_id

2019-001979-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17479

Identifier Type: -

Identifier Source: org_study_id