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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Medullary Thyroid Cancer
• Intervention / Treatment: Drug: Selpercatinib; Drug: Cabozantinib; Drug: Vandetanib

Detailed Description

Adaptive sample size re-estimation will be performed at interim analysis. The sample size could be increased from approximately 250 to 400 depending on the results of interim analysis.

• Study Type: Interventional
• Enrollment (Actual): 291
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3050
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Instituto Nacional de Câncer - INCA
  • Rio de Janeiro, Brazil, 22250-905
    • Grupo Oncoclínicas Botafogo
  • Rio de Janeiro, Brazil, 22775-001
    • Grupo COI - Clínicas Oncológicas Integradas
  • São Paulo, Brazil, 01246-000
    • ICESP - Instituto do Cancer do Estado de Sao Paulo
  • São Paulo, Brazil, 01452-000
    • Centro Paulista de Oncologia Clínica
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30380-680
      • Oncocentro
  • Paraná
    • Londrina, Paraná, Brazil, 86015-520
      • Hospital de Cancer de Londrina
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Fundação Pio XII - Hospital de Câncer de Barretos
    • Campinas, São Paulo, Brazil, 13060-904
      • Centro de Pesquisa Sao Lucas
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Hospital de Clínicas de Ribeirão Preto
    • São Paulo, São Paulo, Brazil, 04543-000
      • Instituto D'Or de Pesquisa e Ensino (IDOR)
    • São Paulo, São Paulo, Brazil, 01308-060
      • Hospital Sírio Libanês
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• China
  • Anhui
    • Hefei, Anhui, China, 230071
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Tongren Hospital Affiliated to Capital Medical University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Gansu Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Centre
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
  • Jilin
    • Changchun, Jilin, China, 132000
      • Jilin Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital
• Czechia
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc
  • Brno-město
    • Brno, Brno-město, Czechia, 625 00
      • Fakultní nemocnice Brno Bohunice
  • Praha 5
    • Prague, Praha 5, Czechia, 150 06
      • Fakultni nemocnice Motol
• France
  • Alsace
    • Strasbourg, Alsace, France, 67065
      • Centre Paul Strauss
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33076
      • Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France, 69008
      • Centre Leon Berard
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13915
      • Assistance Publique Hôpitaux de Marseille - Hôpital Nord
  • Calvados
    • Caen, Calvados, France, 14076
      • Centre Francois Baclesse
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • Centre Georges François Leclerc
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
      • Centre Hospitalier Universitaire d'Angers
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Claude Huriez - CHU de Lille
  • Orne
    • Paris, Orne, France, 75013
      • Pitie Salpetriere University Hospital
  • Puy-de-Dôme
    • Clermont-Ferrand, Puy-de-Dôme, France, 63011
      • Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Gustave Roussy
• Germany
  • Berlin, Germany, 10117
    • Charité Universitaetsmedizin Berlin - Campus Mitte
  • Hamburg, Germany, 20251
    • Hämato-Onkologie Hamburg, Prof. Laack und Partner
  • Bavaria
    • München, Bavaria, Germany, 81337
      • Klinikum der Universität München Großhadern
    • Würzburg, Bavaria, Germany, 97080
      • Klinikum der Universität München Großhadern
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45122
      • Universitaetsklinikum Essen
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin Johannes Gutenberg Universität Mainz
  • Saxony-Anhalt
    • Magdeburg, Saxony-Anhalt, Germany, 39120
      • Otto-von-Guericke-Universität Magdeburg
• Greece
  • Attikí
    • Athens, Attikí, Greece, 115 28
      • Alexandra Hospital
  • Irakleío
    • Heraklion, Irakleío, Greece, 711 10
      • University General Hospital of Heraklion
  • Thessaloniki
    • Thessaloniki, Thessaloniki, Greece, 570 01
      • European Interbalkan Medical Center
• India
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education & Research (PGIMER)
  • Kerala
    • Thiruvananthapuram, Kerala, India, 695011
      • Regional Cancer Centre - Thiruvananthapuram
  • Maharashtra
    • Nashik, Maharashtra, India, 422001
      • HCG Manavata Cancer Centre
    • Pune, Maharashtra, India, 411004
      • Deenanath Mangeshkar Hospital & Research Centre
    • Pune, Maharashtra, India, 411001
      • Grant Medical Foundation - Ruby Hall Clinic
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Apollo Gleneagles Hospitals Kolkata
• Israel
  • Central District
    • Petah Tikva, Central District, Israel, 4941492
      • Rabin Medical Center
    • Ramat Gan, Central District, Israel, 5265601
      • Sheba Medical Center
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 9112001
      • Hadassah Medical Center
• Italy
  • Catania, Italy, 95124
    • Azienda Ospedaliera Garibaldi
  • Campania
    • Napoli, Campania, Italy, 80131
      • University of Naples Federico II
  • Lazio
    • Rome, Lazio, Italy, 00161
      • Policlinico Umberto I
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano
    • Milan, Milano, Italy, 20122
      • Istituto Auxologico Italiano
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
  • Roma
    • Rome, Roma, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena
  • Tuscany
    • Pisa, Tuscany, Italy, 56124
      • Azienda Ospedaliera Universitaria Pisana
    • Siena, Tuscany, Italy, 53100
      • Ospedale Le Scotte
  • Veneto
    • Padua, Veneto, Italy, 35128
      • Istituto Oncologico Veneto IRCCS
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0017
      • Kobe University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • Japanese Foundation for Cancer Research
• Netherlands
  • Groningen, Netherlands, 9713 GR
    • University Medical Center Groningen
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht UMC+
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum
• Poland
  • Silesian Voivodeship
    • Gliwice, Silesian Voivodeship, Poland, 44-101
      • Narodowy Instytut Onkologii - Oddzial w Gliwicach
  • Świętokrzyskie Voivodeship
    • Kielce, Świętokrzyskie Voivodeship, Poland, 25-734
      • Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej
• Russia
  • Chelyabinsk Oblast
    • Chelyabinsk, Chelyabinsk Oblast, Russia, 454048
      • Clinic Evimed
  • Kalužskaja Oblast'
    • Obninsk, Kalužskaja Oblast', Russia, 249036
      • A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological
  • Moscow
    • Moscow, Moscow, Russia, 115478
      • Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
    • Moscow, Moscow, Russia, 117292
      • Endocrinology Research Center of Rosmedtechnologies
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 198255
      • Saint-Petersburg City Clinical Oncology Dispensary
    • Saint Petersburg, Sankt-Peterburg, Russia, 190020
      • Saint Petersburg State University
• South Korea
  • Chungcheongbuk-do [Chungbuk]
    • Jungbuk, Chungcheongbuk-do [Chungbuk], South Korea, 28644
      • Chungbuk National University Hospital
  • Kyǒnggi-do
    • Goyang-si, Kyǒnggi-do, South Korea, 10408
      • National Cancer Center
    • Seongnam, Kyǒnggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 3080
      • Seoul National University Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 3722
      • Severance Hospital, Yonsei University Health System
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 6351
      • Samsung Medical Center
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 8035
      • Hospital Universitari Vall d'Hebron
  • Catalunya [Cataluña]
    • L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain, 8907
      • Instituto Catalan de Oncologia - Hospital Duran I Reynals
  • Girona [Gerona]
    • Girona, Girona [Gerona], Spain, 17007
      • Institut Català d'Oncologia (ICO) - Girona
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28034
      • Hospital Universitario Ramon y Cajal
    • Madrid, Madrid, Comunidad de, Spain, 28027
      • Clinica Universidad de Navarra
    • Madrid, Madrid, Comunidad de, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Madrid, Madrid, Comunidad de, Spain, 28046
      • Hospital Universitario La Paz
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• United Kingdom
  • Cardiff [Caerdydd Gb-crd]
    • Cardiff, Cardiff [Caerdydd Gb-crd], United Kingdom, CF14 2TL
      • Velindre Cancer Centre
  • England
    • Sheffield, England, United Kingdom, S10 2SJ
      • Weston Park Hospital
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, g12OYN
      • Gartnavel General Hospital
  • Kensington and Chelsea
    • London, Kensington and Chelsea, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital (Chelsea)
  • London, City of
    • London, London, City of, United Kingdom, NW1 2PG
      • University College London Hospital
  • Sutton
    • London, Sutton, United Kingdom, SM2 5PT
      • Royal Marsden Hospital (Sutton)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010-0269
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology - Westwood (Building 100)
    • Sacramento, California, United States, 95817
      • University of California Davis (UC Davis) Comprehensive Cancer Center
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10017
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• At least 18 years of age (participants as young as 12 years of age will be allowed if permitted by local regulatory authorities).
• Histologically or cytologically confirmed, unresectable, locally advanced and/or metastatic MTC and no prior history of treatment with kinase inhibitors for advanced/metastatic disease.
• Radiographic progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at screening compared with a previous image taken within the prior 14 months as assessed by the BICR. Participants with measurable or non-measurable but evaluable disease are eligible; however, participants with non-measurable disease may not have disease limited to bone sites only.

• A defined/acceptable RET gene alteration identified in a tumor, germline deoxyribonucleic acid (DNA) or blood sample.

  • Tumor tissue in sufficient quantity to allow for retrospective central analysis of RET mutation status
• Eastern Cooperative Oncology Group performance status score of 0 to 2.
• Adequate hematologic, hepatic, and renal function and electrolytes.
• Men and women of childbearing potential must agree to use a highly effective contraceptive method during treatment with study drug and for 4 months following the last dose of study drug.
• Ability to swallow capsules.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selpercatinib - Treatment A (TRT A); 160 milligrams Selpercatinib administered orally (PO) twice daily (BID). Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).	Drug: Selpercatinib; Administered orally; Other Names: LOXO-292; LY3527723
Active Comparator: Cabozantinib or Vandetanib - Treatment B (TRT B); 140 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	Drug: Cabozantinib; Administered orally; Drug: Vandetanib; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)	TFFS by BICR is defined as the time from randomization to the first occurrence of: documented radiographic disease progression per RECIST 1.1 as assessed by BICR; or; unacceptable toxicity leading to treatment discontinuation as assessed by the investigator. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. To qualify as an event, the toxicity must be from an intolerable AE (defined as any study drug-related AE that meets protocol guidance for treatment discontinuation, with the exception of alopecia); or death (due to any cause).	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	ORR is defined as the number of participants who achieved the best overall response (BOR) of CR or PR divided by the total number of participants randomized to each treatment arm. ORR per RECIST 1.1 as assessed by BICR.	Baseline through Disease Progression or Death Up to 39 Months
Duration of Response (DoR) by BICR	DoR by BICR is defined as the time from the date that measurement criteria for complete response (CR) or partial response (PR) (whichever is first recorded) are first met by the BICR or investigator assessment, as applicable, until the first date that disease is recurrent or documented disease progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. 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.	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months
Overall Survival (OS)	Overall survival (OS) is defined as the time from randomization until death from any cause. If the participant is 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
PFS2 by Investigator	Progression-free survival 2 (PFS2) is defined as the time from randomization to disease progression (radiographic or symptomatic progression as determined by the investigator) on the next line of treatment or death from any cause in the absence of observed disease progression. If the participant is alive at the cutoff for analysis, and disease progression has not been observed, PFS2 data will be censored on the latest date of last progression-free assessment or start of the next line of treatment.	Baseline
Comparative Tolerability: Number of Weeks With High Side Effect Bother Based Score of 3 or 4 on the Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5)	Comparative tolerability defined as a comparison of the proportion of time on treatment with high side effect bother as assessed by the FACT-GP5. The FACT-GP5 is a single question used to assess the overall bother of the treatment side effects. It is scored using a 5-point rating scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; and 4 = very much), where lower scores reflect less bother from treatment side effects. Time with high side effect bother (i.e.) score of 3 or 4 is reported here and was derived as follows: cumulative amount of time, in weeks, during which a participant reports high side effect bother divided by the total duration of therapy (weeks), derived as (date of last study treatment dose - date of first study treatment dose + 1) divided by 7.	Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months

Collaborators and Investigators

• Sponsor: Loxo Oncology, Inc.
• Collaborators: Eli Lilly and Company
• Investigators: 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

Publications and helpful links

General Publications

• Wirth 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.
• Jaber 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.
• Hadoux 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.

Helpful Links

• A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2020
• Primary Completion (Actual): May 22, 2023
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 24, 2019
• First Submitted That Met QC Criteria: December 24, 2019
• First Posted (Actual): December 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: targeted therapy; medullary thyroid carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Neuroendocrine; Carcinoma, Medullary; cabozantinib; selpercatinib; vandetanib
• Other Study ID Numbers: 17478; J2G-MC-JZJB (Other Identifier: Eli Lilly and Company); 2019-001978-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No