A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
LIBRETTO-531
A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing Selpercatinib to Physicians Choice of Cabozantinib or Vandetanib in Patients With Progressive, Advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)
3 other identifiers
interventional
291
20 countries
143
Brief Summary
The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2020
Longer than P75 for phase_3
143 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 24, 2019
CompletedFirst Posted
Study publicly available on registry
December 26, 2019
CompletedStudy Start
First participant enrolled
February 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 22, 2023
CompletedResults Posted
Study results publicly available
June 13, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2027
ExpectedMarch 19, 2026
March 1, 2026
3.3 years
December 24, 2019
March 12, 2024
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
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 1.1) criteria, or death from any cause in the absence of BICR-documented progressive disease. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months
Secondary Outcomes (7)
Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR
Baseline through Disease Progression or Death Up to 39 Months
Duration of Response (DoR) by BICR
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months
Overall Survival (OS)
Baseline
PFS2 by Investigator
Baseline
- +2 more secondary outcomes
Study Arms (2)
Selpercatinib - Treatment A (TRT A)
EXPERIMENTAL160 milligrams Selpercatinib administered orally (PO) twice daily (BID). Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).
Cabozantinib or Vandetanib - Treatment B (TRT B)
ACTIVE COMPARATOR140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice. Cabozantinib Adolescent Dose: 40 mg/m2. Vandetanib Adolescent Dose: * 0.7 - \<0.9 - 100 mg every other day (QOD) * 0.9 - \<1.2 - 100 mg QD * 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg * ≥1.6 - 200 QD
Interventions
Administered orally
Eligibility Criteria
You may not qualify if:
- An additional validated oncogenic driver in MTC if known that could cause resistance to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF gene mutations and NTRK gene fusions.
- Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression.
- Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months, history of Torsades de pointes, or prolongation of the QTcF \>470 milliseconds on more than one electrocardiogram (ECG) during screening. Participants who are intended to receive vandetanib if randomized to the control arm are ineligible if QTcF is \>450 milliseconds.
- Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing uncontrolled intercurrent illness.
- Active hemorrhage or at significant risk for hemorrhage.
- Other malignancy unless nonmelanoma skin cancer, carcinoma in situ or malignancy diagnosed ≥2 years previously and not currently active. Participants with multiple endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companycollaborator
- Loxo Oncology, Inc.lead
Study Sites (143)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
City of Hope National Medical Center
Duarte, California, 91010-0269, United States
UCLA Hematology/Oncology - Westwood (Building 100)
Los Angeles, California, 90095, United States
University of California Davis (UC Davis) Comprehensive Cancer Center
Sacramento, California, 95817, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502, United States
Emory University
Atlanta, Georgia, 30322, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10017, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19114, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792, United States
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3050, Australia
Sir Charles Gairdner Hospital
Perth, Western Australia, 6009, Australia
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
Liège, 4000, Belgium
Oncocentro
Belo Horizonte, Minas Gerais, 30380-680, Brazil
Hospital de Cancer de Londrina
Londrina, Paraná, 86015-520, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, São Paulo, 14784400, Brazil
Centro de Pesquisa Sao Lucas
Campinas, São Paulo, 13060-904, Brazil
Hospital de Clínicas de Ribeirão Preto
Ribeirão Preto, São Paulo, 14051-140, Brazil
Hospital Sírio Libanês
São Paulo, São Paulo, 01308-060, Brazil
Instituto D'Or de Pesquisa e Ensino (IDOR)
São Paulo, São Paulo, 04543-000, Brazil
Instituto Nacional de Câncer - INCA
Rio de Janeiro, 20230-130, Brazil
Grupo Oncoclínicas Botafogo
Rio de Janeiro, 22250-905, Brazil
Grupo COI - Clínicas Oncológicas Integradas
Rio de Janeiro, 22775-001, Brazil
Icesp - Instituto Do Câncer Do Estado de São Paulo
São Paulo, 01246-000, Brazil
Centro Paulista de Oncologia Clínica
São Paulo, 01452-000, Brazil
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Anhui Provincial Hospital
Hefei, Anhui, 230071, China
Beijing Tongren Hospital affiliated to Capital Medical University
Beijing, Beijing Municipality, 100730, China
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, 400030, China
The First Affiliated Hospital Of Fujian Medical University
Fuzhou, Fujian, 350005, China
Gansu Cancer Hospital
Lanzhou, Gansu, 730050, China
Sun Yat-Sen University Cancer Centre
Guangzhou, Guangdong, 510060, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081, China
Henan Cancer Hospital
Zhengzhou, Henan, 450008, China
Hunan Cancer Hospital
Changsha, Hunan, 410013, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210000, China
Jilin Cancer Hospital
Changchun, Jilin, 132000, China
Jinan Central Hospital
Jinan, Shandong, 250013, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032, China
West China Hospital, Sichuan University
Chengdu, Sichuan, 610041, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060, China
First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650032, China
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang, 310014, China
Sir Run Run Shaw Hospital
Hangzhou, Zhejiang, 310016, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Fakultní nemocnice Brno Bohunice
Brno, Brno-město, 625 00, Czechia
Fakultni nemocnice Motol
Prague, Praha 5, 150 06, Czechia
Fakultni nemocnice Olomouc
Olomouc, 779 00, Czechia
Centre Paul Strauss
Strasbourg, Alsace, 67065, France
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux, Aquitaine, 33076, France
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69008, France
Assistance Publique Hôpitaux de Marseille - Hôpital Nord
Marseille, Bouches-du-Rhône, 13915, France
Centre François Baclesse
Caen, Calvados, 14076, France
Centre Georges François Leclerc
Dijon, Côte-d'Or, 21079, France
Institut Claudius Regaud
Toulouse, Haute-Garonne, 31059, France
Centre Hospitalier Universitaire d'Angers
Angers, Maine-et-Loire, 49933, France
Hopital Claude Huriez - CHU de Lille
Lille, Nord, 59037, France
Pitie Salpetriere University Hospital
Paris, Orne, 75013, France
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
Clermont-Ferrand, Puy-de-Dôme, 63011, France
Gustave Roussy
Villejuif, Val-de-Marne, 94800, France
Klinikum der Universität München Großhadern
München, Bavaria, 81337, Germany
Klinikum der Universität München Großhadern
Würzburg, Bavaria, 97080, Germany
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625, Germany
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45122, Germany
Universitätsmedizin Johannes Gutenberg Universität Mainz
Mainz, Rhineland-Palatinate, 55131, Germany
Otto-von-Guericke-Universität Magdeburg
Magdeburg, Saxony-Anhalt, 39120, Germany
Charité Universitaetsmedizin Berlin - Campus Mitte
Berlin, 10117, Germany
Hämato-Onkologie Hamburg, Prof. Laack und Partner
Hamburg, 20251, Germany
Alexandra Hospital
Athens, Attikí, 115 28, Greece
University General Hospital of Heraklion
Heraklion, Irakleío, 711 10, Greece
European Interbalkan Medical Center
Thessaloniki, Thessaloniki, 570 01, Greece
Regional Cancer Centre - Thiruvananthapuram
Thiruvananthapuram, Kerala, 695011, India
HCG Manavata Cancer Centre
Nashik, Maharashtra, 422001, India
Grant Medical Foundation - Ruby Hall Clinic
Pune, Maharashtra, 411001, India
Deenanath Mangeshkar Hospital & Research Centre
Pune, Maharashtra, 411004, India
Apollo Gleneagles Hospitals Kolkata
Kolkata, West Bengal, 700054, India
Post Graduate Institute of Medical Education & Research (PGIMER)
Chandigarh, 160012, India
Rabin Medical Center
Petah Tikva, Central District, 4941492, Israel
Sheba Medical Center
Ramat Gan, Central District, 5265601, Israel
Hadassah Medical Center
Jerusalem, Jerusalem, 9112001, Israel
University of Naples Federico II
Naples, Campania, 80131, Italy
Policlinico Umberto I
Rome, Lazio, 00161, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133, Italy
Istituto Auxologico Italiano
Milan, Milano, 20122, Italy
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
Turin, Piedmont, 10126, Italy
Istituto Nazionale Tumori Regina Elena
Rome, Roma, 00144, Italy
Azienda Ospedaliera Universitaria Pisana
Pisa, Tuscany, 56124, Italy
Ospedale Le Scotte
Siena, Tuscany, 53100, Italy
Istituto Oncologico Veneto IRCCS
Padua, Veneto, 35128, Italy
Azienda Ospedaliera Garibaldi
Catania, 95124, Italy
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, 464-8681, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648, Japan
Kobe University Hospital
Kobe, Hyōgo, 650-0017, Japan
Yokohama City University Hospital
Yokohama, Kanagawa, 236-0004, Japan
Osaka University Hospital
Suita, Osaka, 565-0871, Japan
Japanese Foundation for Cancer Research
Koto, Tokyo, 135-8550, Japan
National Hospital Organization Kyushu Medical Center
Fukuoka, 810-8563, Japan
Maastricht UMC+
Maastricht, Limburg, 6229 HX, Netherlands
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
Amsterdam, North Holland, 1066 CX, Netherlands
Leids Universitair Medisch Centrum
Leiden, South Holland, 2333 ZA, Netherlands
University Medical Center Groningen
Groningen, 9713 GR, Netherlands
Narodowy Instytut Onkologii - Oddzial w Gliwicach
Gliwice, Silesian Voivodeship, 44-101, Poland
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej
Kielce, Świętokrzyskie Voivodeship, 25-734, Poland
Clinic Evimed
Chelyabinsk, Chelyabinsk Oblast, 454048, Russia
A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological
Obninsk, Kalužskaja Oblast', 249036, Russia
Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
Moscow, Moscow, 115478, Russia
Endocrinology Research Center of Rosmedtechnologies
Moscow, Moscow, 117292, Russia
Saint Petersburg State University
Saint Petersburg, Sankt-Peterburg, 190020, Russia
Saint-Petersburg City Clinical Oncology Dispensary
Saint Petersburg, Sankt-Peterburg, 198255, Russia
Chungbuk National University Hospital
Jungbuk, Chungcheongbuk-do [Chungbuk], 28644, South Korea
National Cancer Center
Goyang-si, Kyǒnggi-do, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam, Kyǒnggi-do, 13620, South Korea
Seoul National University Hospital
Seoul, Seoul-teukbyeolsi [Seoul], 3080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, Seoul-teukbyeolsi [Seoul], 3722, South Korea
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], 6351, South Korea
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [Barcelona], 8035, Spain
Instituto Catalan de Oncologia - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Catalunya [Cataluña], 8907, Spain
Institut Català d'Oncologia (ICO) - Girona
Girona, Girona [Gerona], 17007, Spain
Clinica Universidad de Navarra
Madrid, Madrid, Comunidad de, 28027, Spain
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Comunidad de, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, Madrid, Comunidad de, 28041, Spain
Hospital Universitario La Paz
Madrid, Madrid, Comunidad de, 28046, Spain
Hospital Universitario Virgen de la Victoria
Málaga, Málaga, 29010, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, 31008, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28009, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Velindre Cancer Centre
Cardiff, Cardiff [Caerdydd Gb-crd], CF14 2TL, United Kingdom
Weston Park Hospital
Sheffield, England, S10 2SJ, United Kingdom
Gartnavel General Hospital
Glasgow, Glasgow City, g12OYN, United Kingdom
Royal Marsden Hospital (Chelsea)
London, Kensington and Chelsea, SW3 6JJ, United Kingdom
University College London Hospital
London, London, City of, NW1 2PG, United Kingdom
Royal Marsden Hospital (Sutton)
London, Sutton, SM2 5PT, United Kingdom
Related Publications (4)
Payakachat N, Gilligan AM, Altman D, Maeda P, Choi J, Bourke S, Speck RM, Spies E, Kopeckova K, Elisei R, Wadsley J, Krajewska J. Assessing side-effect bother, burden, and tolerability: A qualitative study exploring the content validity of the Functional Assessment of Cancer Therapy - Item GP5. J Geriatr Oncol. 2025 Sep;16(7):102304. doi: 10.1016/j.jgo.2025.102304. Epub 2025 Jul 4.
PMID: 40617171DERIVEDHadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Fuhrer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. doi: 10.1056/NEJMoa2309719. Epub 2023 Oct 21.
PMID: 37870969DERIVEDWirth LJ, Brose MS, Elisei R, Capdevila J, Hoff AO, Hu MI, Tahara M, Robinson B, Gao M, Xia M, Maeda P, Sherman E. LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naive RET-mutant medullary thyroid cancer. Future Oncol. 2022 Sep;18(28):3143-3150. doi: 10.2217/fon-2022-0657. Epub 2022 Aug 15.
PMID: 35969032DERIVEDJaber T, Dadu R, Hu MI. Medullary thyroid carcinoma. Curr Opin Endocrinol Diabetes Obes. 2021 Oct 1;28(5):540-546. doi: 10.1097/MED.0000000000000662.
PMID: 34292174DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
December 24, 2019
First Posted
December 26, 2019
Study Start
February 11, 2020
Primary Completion
May 22, 2023
Study Completion (Estimated)
November 1, 2027
Last Updated
March 19, 2026
Results First Posted
June 13, 2024
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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.