A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)

Carcinoma, Non-Small-Cell Lung Clinical Trial

— LIBRETTO-432  

Official title:

LIBRETTO-432: A Placebo-controlled Double-Blinded Randomized Phase 3 Study of Adjuvant Selpercatinib Following Definitive Locoregional Treatment in Participants With Stage IB-IIIA RET Fusion-Positive NSCLC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04819100
• Other study ID #: 18126
• Secondary ID: J2G-MC-JZJX2020-
• Status: Recruiting
• Phase: Phase 3
• Start date: December 20, 2021
• Est. completion date: August 30, 2032

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: There may be multiple sites in this clinical trial. 1-877-CTLILL
• Phone: 1-317-615-4559
• Email: ClinicalTrials.gov[@]lilly.com
• 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 placebo is effective and safe in delaying cancer return in participants with early-stage non-small cell lung cancer (NSCLC), who have already had surgery or radiation. Participants who are assigned to placebo and stop the study drug because their disease comes back or gets worse have the option to potentially crossover to selpercatinib. Participation could last up to three years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: August 30, 2032
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have histologically confirmed Stage IB, II, or IIIA NSCLC.

• Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR), next generation sequencing (NGS), or another molecular test per sponsor's approval.

• Must have received definitive locoregional therapy with curative intent (surgery or radiotherapy) for Stage IB, II, or IIIA NSCLC.

-- Must have undergone the available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, based on the investigator's discretion.

• Maximum time allowed between definitive therapy completion and randomization must be:

• 10 weeks if no chemotherapy was administered

• 26 weeks if adjuvant chemotherapy was administered

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• 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 the study and for at least 2 weeks after last dose of study drug.

Exclusion Criteria:

• Additional oncogenic drivers in NSCLC, if known.

• Evidence of small cell lung cancer.

• Clinical or radiologic evidence of disease recurrence or progression following definitive therapy.

• Known or suspected interstitial fibrosis or interstitial lung disease or history of (noninfectious) pneumonitis that required steroids.

• Clinically significant active cardiovascular disease or history of myocardial infarction within six months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) greater than 470 milliseconds.

• Have known uncontrolled human immunodeficiency virus (HIV)-1/2 infection.

• Have known active hepatitis B or C.

• Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment.

• Major surgery within 4 weeks prior to planned start of selpercatinib.

• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.

• Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers or a malignancy diagnosed greater than or equal to two years previously and not currently active.

• Pregnancy or lactation.

• Prior treatment with a selective RET inhibitor (e.g. selpercatinib or pralsetinib).

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Selpercatinib
Administered orally.
• Placebo
Administered orally.

Locations

Country	Name	City	State
Australia	Border Medical Oncology	Albury	New South Wales
Australia	Ballarat Health Services	Ballarat Central	Victoria
Australia	Bendigo Health Care Group	Bendigo	Victoria
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Rockhampton Hospital	Rockhampton	Queensland
Australia	Goulburn Valley Health	Shepparton	Victoria
Australia	The Townsville Hospital	Townsville	Queensland
Australia	South West Healthcare	Warrnambool	Victoria
Austria	Landeskrankenhaus Feldkirch	Feldkirch	Vorarlberg
Austria	Klinik Floridsdorf	Wien
Belgium	Cliniques universitaires Saint-Luc	Brussels	Bruxelles-Capitale, Région De
Belgium	Antwerp University Hospital	Edegem	Antwerpen
Belgium	CHU UCL Namur/Site Sainte Elisabeth	Namur
Belgium	Clinique Saint Pierre	Ottignies	Wallonne, Région
Belgium	AZ Delta vzw	Roeselare	West-Vlaanderen
Belgium	Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant-Godinne - Site Godinne	Yvoir	Namur
Brazil	Centro Avançado de Tratamento Oncológico- CENANTRON	Belo Horizonte	Minas Gerais
Brazil	Sirio-Libanes Brasilia - Centro de Oncologia - Asa Sul	Brasilia	Distrito Federal
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Câncer de Recife	Recife	Pernambuco
Brazil	Grupo COI - Clínicas Oncológicas Integradas	Rio de Janeiro
Brazil	Nucleo de Oncologia da Bahia	Salvador	Bahia
Brazil	Hospital BP	Sao Paulo	São Paulo
Brazil	Instituto D'Or de Pesquisa e Ensino (IDOR)	Sao Paulo	São Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	Sao Paulo	São Paulo
Brazil	Centro Paulista de Oncologia Clínica	São Paulo
Brazil	Núcleo de Pesquisa Clínica da Rede São Camilo	São Paulo
Brazil	Centro Oncológico do Triângulo	Uberlândia	Minas Gerais
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
China	Beijing Friendship Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Xiangya Hospital, Central South University	Changsha	Hunan
China	the Third People's Hospital of Chengdu	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	Beijing Cancer hospital	Haidian District	Beijing
China	First Affiliated Hosp of College of Med, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Jinan Central Hospital	Jinan	Shandong
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Tangdu Hospital of Fourth Military Medical University of Chinese People's Liberation Army	Xi'an	Shaanxi
Czechia	Masarykuv onkologicky ustav	Brno	Brno-mesto
Czechia	Nemocnice AGEL Ostrava - Vitkovice a.s	Ostrava	Ostrava Mesto
Czechia	Fakultni nemocnice Bulovka	Prague	Praha 8
Denmark	Odense Universitetshospital	Odense	Syddanmark
France	Centre Chirurgical Marie Lannelongue	Le Plessis-Robinson	Hauts-de-Seine
France	Hospices Civils de Lyon - Hopital Louis Pradel	Lyon	Rhône
France	Centre Leon Berard	Lyon CEDEX 08	Rhône-Alpes
France	Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone	Marseille	Bouches-du-Rhône
France	Hopitaux Universitaires Paris Centre-Hopital Cochin	Paris
France	CHU Charles Nicolle	Rouen	Haute-Normandie
Germany	Charite Universitätsmedizin Berlin Campus Benjamin Franklin	Berlin
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Asklepios Fachkliniken München-Gauting	Gauting	Bayern
Germany	Franziskus-Hospital Harderberg	Georgsmarienhütte	Niedersachsen
Germany	LungenClinic Grosshansdorf	Grosshansdorf	Schleswig-Holstein
Germany	Asklepios Klinik Harburg	Hamburg
Germany	KRH, Klinikum Siloah	Hannover	Niedersachsen
Germany	Thoraxklinik-Heidelberg gGmbH	Heidelberg	Baden-Württemberg
Germany	Lungenfachklinik Immenhausen	Immenhausen	Hessen
Germany	Klinik Löwenstein	Löwenstein	Baden-Württemberg
Germany	Klinikum der Ludwig-Maximilians-Universitaet Muenchen	München	Bayern
Germany	Universitätsklinikum Münster - Albert Schweitzer Campus	Münster	Nordrhein-Westfalen
Greece	Agios Savvas Regional Cancer Hospital	Athens	Attikí
Greece	Errikos Dunant Hospital Center	Athens	Attikí
Greece	Sotiria Thoracic Diseases Hospital of Athens	Athens	Attikí
Greece	University General Hospital of Heraklion	Heraklion	Irakleío
Greece	University Hospital of Patras	Patras	Acha?a
Greece	European Interbalkan Medical Center	Thessaloniki	Thessaloníki
Greece	G. Papanikolaou General Hospital	Thessaloniki	Thessaloníki
Hong Kong	Hong Kong United Oncology Centre	Hong Kong
Hong Kong	Princess Margaret Hospital	Lai Chi Kok
Hong Kong	Queen Elizabeth Hospital	Yau Ma Tei
India	Tata Memorial Hospital	Mumbai	Maharashtra
India	Rashtrasant Tukdoji Regional Cancer Hospital	Nagpur	Maharashtra
India	HCG Manavata Cancer Centre	Nashik	Maharashtra
India	Rajiv Gandhi Cancer Institute And Research Centre	New Delhi	Delhi
India	Regional Cancer Centre - Thiruvananthapuram	Thiruvananthapuram	Kerala
Israel	Rambam Health Care Campus	Haifa	?eifa
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Sheba Medical Center	Ramat Gan	HaMerkaz
Italy	Instituto Tumori Giovanni Paolo II	Bari	Puglia
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan	Milano
Italy	Azienda Ospedaliera Dei Colli	Naples	Napoli
Italy	Azienda Sanitaria Ospedaliera S Luigi Gonzaga	Orbassano	Torino
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	Humanitas	Rozzano	Milano
Japan	Himeji Medical Center	Himeji	Hyogo
Japan	Hiroshima University Hospital	Hiroshima
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Japanese Foundation for Cancer Research	Koto	Tokyo
Japan	Tominaga Hospital	Nagaizumi	Shizuoka
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka
Japan	Kanagawa cancer center	Yokohama	Kanagawa
Japan	Tottori University Hospital	Yonago	Tottori
Korea, Republic of	Pusan National University Hospital	Busan	Pusan-Kwangyokshi
Korea, Republic of	Kyungpook National University Chilgok Hospital	Deagu	Taegu-Kwangyokshi
Korea, Republic of	National Cancer Center	Goyang-si	Kyonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeonranamdo
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Korea University Guro Hospital	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
Mexico	Oncare Viaducto Napoles	Cdmx	México
Mexico	Actualidad Basada en la Investigación del Cáncer	Guadalajara	Jalisco
Mexico	Avix Investigación Clinica, S.C.	Monterrey	Nuevo León
Mexico	Hospital Universitario ""Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo León
Netherlands	Ziekenhuis St. Jansdal	Harderwijk	Gelderland
Netherlands	Radboudumc	Nijmegen	Gelderland
Norway	Oslo Universitetssykehus Ullevål	Oslo
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie	Warszawa	Mazowieckie
Puerto Rico	Pan American Center for Oncology Trials	Rio Piedras
Romania	Institutul Oncologic	Cluj
Russian Federation	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk	Arkhangel'skaya Oblast'
Russian Federation	Hadassah Medical	Moscow	Moskva
Russian Federation	First Pavlov State Medical University of Saint Petersburg	Saint Petersburg	Sankt-Peterburg
Russian Federation	Scientific research institution of oncology named after N.N. Petrov	Sankt-Peterburg
Singapore	Parkway Cancer Centre - Gleneagles Hospital	Singapore	Central Singapore
Singapore	Tan Tock Seng Hospital	Singapore	Central Singapore
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Institut Català d'Oncologia (ICO) - Badalona	Badalona	Barcelona [Barcelona]
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya [Cataluña]
Spain	Hospital Universitari Dexeusa	Barcelona	Catalunya [Cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Parc de Salut Mar - Hospital del Mar	Barcelona	Barcelona [Barcelona]
Spain	Hospital Universitario Puerta del Mar	Cádiz	Andalucía
Spain	Hospital Universitario Reina Sofia	Cordoba	Andalucía
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	El Palmar, Murcia	Murcia, Región De
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals	L'Hospitalet Del Llobregat	Barcelona [Barcelona]
Spain	Hospital Universitario de Canarias	La Laguna	Santa Cruz De Tenerife
Spain	Complejo Asistencial Universitario de León - Hospital de León	León	Castilla Y León
Spain	Hospital Lucus Augusti	Lugo	Lugo [Lugo]
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad De
Spain	MD Anderson Cancer Center	Madrid
Spain	Hospital Regional Universitario	Málaga
Spain	Hospital de Mataró"	Mataró	Barcelona [Barcelona]
Spain	Complexo Hospitalario Universitario de Ourense	Ourense	Ourense [Orense]
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Son Llàtzer	Palma	Illes Balears [Islas Baleares]
Spain	CHUVI- Hospital Alvaro Cunqueiro	Pontevedra	Pontevedra [Pontevedra]
Spain	Hospital Universitari Sant Joan de Reus	Reus	Tarragona [Tarragona]
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [La Coruña]
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	València
Sweden	Sahlgrenska Universitetssjukhuset	Gothenburg	Västra Götalands Län [se-14]
Taiwan	Changhua Christian Hospital	Changhua County	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital at Kaohsiung	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung City	Taichung
Taiwan	Chi Mei Hospital - Liouying Branch	Tainan City	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	National Taiwan University Cancer Center (NTUCC)	Taipei City	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch	Taoyuan
Turkey	Adana City Hospital	Adana
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center	Adana	Diyarbakir
Turkey	Ankara Bilkent Sehir Hastanesi	Ankara
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Memorial Antalya Hospital	Antalya
Turkey	Ege Universitesi Hastanesi	Bornova	Izmir
Turkey	Uludag Universitesi	Bursa
Turkey	Dicle Üniversitesi	Diyarbakir
Turkey	Trakya University	Edirne
Turkey	Acibadem Maslak Hastanesi	Istanbul
Turkey	Medipol Mega Universite Hastanesi	Istanbul
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Izmir Katip Celebi Universitesi Ataturk Egitim Ve Arastrma Hastanesi	Izmir
Turkey	Izmir Medical Park Hospital	Izmir, Karsiyaka	Izmir
Turkey	Inönü Üniversitesi Turgut Özal Tip Merkezi Egitim ve Arastirma	Malatya
Ukraine	Sumy regional clinical oncological dispensary	Sumy	Sumska Oblast
United Kingdom	Chelsea and Westminster Hospital NHS Foundation Trust	London	England
United Kingdom	Royal Brompton Hospital	London	Kensington And Chelsea
United Kingdom	University College London Hospital	London	London, City Of
United Kingdom	City Hospital, Nottingham University Hospitals	Nottingham
United Kingdom	New Cross Hospital	Wolverhampton
United States	USO - New York Oncology Hematology, P.C.	Albany	New York
United States	USO-Texas Oncology-Central/South Texas	Austin	Texas
United States	GenesisCare	Aventura	Florida
United States	GenesisCare - Boca Raton	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UCLA Hematology/Oncology - Santa Monica	Los Angeles	California
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Tennessee Oncology Nashville	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	Stockton Hematology Oncology Group	Stockton	California
United States	US Oncology	The Woodlands	Texas
United States	USO-New York Oncology Hematology, P.C	The Woodlands	Texas
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Greece,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival (EFS)	EFS by Investigator Assessment in the Primary Analysis Population	Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)
Secondary	EFS	EFS by investigator assessment in the overall population	Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)
Secondary	Overall Survival (OS)	OS	Randomization to death from any cause (estimated as up to 9 years)]
Secondary	EFS	EFS by blinded independent central review (BICR)	Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)]
Secondary	Time to Distant Disease Recurrence in the Central Nervous System (CNS)	Time to distant disease recurrence in the CNS by investigator assessment and BICR	Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)
Secondary	Progression Free Survival on the Next Line of Treatment (PFS2)	PFS2 by investigator assessment	Randomization to disease progression on the next line of treatment or death from any cause (estimated as up to 9 years)
Secondary	Positive Predictive Value (PPV) of Rearranged during Transfection (RET) Tests from Investigator-Identified Laboratories with Respect to the Lilly-Designated RET Test	PPV of RET Tests from Investigator-Identified Laboratories with Respect to the Lilly-Designated RET Test	Baseline
Secondary	Mean Change from Baseline over Time in NSCLC Symptoms	NSCLC symptoms will be measured using the 7-item NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ). The NSCLC-SAQ measures the severity/frequency of the following core symptoms: Cough, pain, dyspnea, fatigue, and appetite. Raw scores range from 0 to 4 and the total score ranges from 0-20. Higher scores represent worse symptoms.	Baseline to treatment discontinuation (estimated as up to 3 years)
Secondary	Mean Change from Baseline over Time in Physical Function	Physical function will be measured by the 5 physical function items in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) (also known as the EORTC IL 19 questionnaire). Raw scores range from 0-20. Higher scores indicate worst function.	Baseline to treatment discontinuation (estimated as up to 3 years)

External Links

•   A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC) (LIBRETTO-432)