Medullary Thyroid CancerPhase 1/2LIBRETTO-121NCT03899792
A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
A Phase 1/2 study testing Selpercatinib in people with Medullary Thyroid Cancer and Infantile Myofibromatosis, run by Eli Lilly and Company at 26 sites in 11 countries.
Trial summary
This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor. Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Medullary Thyroid Cancer, Infantile Myofibromatosis, Infantile Fibrosarcoma
- What is being tested?
- Selpercatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 26 sitesin 11 countries
- Study dates
- 13 Jun 2019to May 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
- Evidence of an activating RET gene alteration in the tumor and/or blood
- Measurable or non-measurable disease
- Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
- Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
- Adequate hematologic, hepatic and renal function.
- Ability to receive study drug therapy orally or via gastric access
- Willingness of men and women of reproductive potential to observe conventional and effective birth control
Who cannot join
- Major surgery within two weeks prior to planned start of LOXO-292
- Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
- Clinically significant active malabsorption syndrome
- Pregnancy or lactation
- Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
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- Uncontrolled symptomatic hypercalcemia or hypocalcemia
- Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
- Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])
Trial locations and contacts
26 sites in 11 countries.
26 sites in 11 countries
United States12 sites
The Children's Hospital for Cancer and Blood Disorders
Aurora, Colorado, 80045
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390-9063
Texas Childrens Hospital
Houston, Texas, 77025
Childrens Hospital of Los Angeles
Los Angeles, California, 90027
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Minnesota Hospital
Minneapolis, Minnesota, 55455
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Nemours Children's Health
Orlando, Florida, 32827
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Seattle Children's Hospital Research Foundation
Seattle, Washington, 98105
Japan4 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
Hiroshima University Hospital
Hiroshima, 734-8551
Kyoto University Hospital
Kyoto, 606-8507
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Australia2 sites
Royal Children's Hospital
Melbourne, Victoria, 3052
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Germany1 site
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69115
Italy1 site
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133
Spain1 site
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [Barcelona], 8035
United Kingdom1 site
University College Hospital - London
London, Greater London, NW1 2BU
About this study
Official title: A Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumors
This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor.
Read the detailed description
This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, participants will be enrolled using a rolling 6 dose escalation scheme. The starting dose of LOXO-292 is equivalent to the adult recommended phase 2 dose of 160 milligrams (mg) twice a day (BID). Once the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) is identified, participants will be enrolled to one of four phase 2 dose expansion cohorts depending on tumor histology and tumor genotype. Cycle length will be 28 days.
- Conditions
- Medullary Thyroid Cancer, Infantile Myofibromatosis, Infantile Fibrosarcoma, Papillary Thyroid Cancer, Soft Tissue Sarcoma
- Being tested
- Selpercatinib
- Keywords
- Loxo, LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET
- Medical subject headings
- Carcinoma, Medullary, Myofibromatosis, Thyroid Cancer, Papillary, Sarcoma, Neoplasms by Site, Neoplasms, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelpercatinibDrug
Also called LOXO-292, LY3527723
Oral LOXO-292
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Medullary Thyroid Cancer (MTC) Group | Experimental | Participants in this cohort had MTC and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle.
The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. Receives: Drug: Selpercatinib |
| Cohort 2: Papillary Thyroid Cancer (PTC) Group | Experimental | Participants in this cohort had PTC and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle.
The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. Receives: Drug: Selpercatinib |
| Cohort 3: Other Cancer Group | Experimental | Participants in this cohort had other (REarranged during Transfection (RET)-altered non-thyroid) cancer and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle.
The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. Receives: Drug: Selpercatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was any of the adverse events that starts on or after the first administration of study drug listed below, as defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
- Any Grade(G) ≥3 nonhematologic toxicity except G3 fatigue, nausea, tendon reflex decrease, weight gain attributable to normal growth and development.
- G3 vomiting/diarrhea was DLT only if it persists >48 h despite standard of care treatment.
- G4 vomiting/diarrhea was DLT regardless of duration.
- Any toxicity, regardless of the NCI CTCAE v5.0 grade, resulting in discontinuation or dose reduction of treatment (except symptoms related to progressive disease (PD)).
- G4/G3 thrombocytopenia with G1 or higher bleeding.
- G4 anemia lasting >8 days, despite supportive therapy.
- G4 neutropenia, lasting >8 days, despite supportive therapy
Measured: Cycle 1 (28 Day Cycle)
Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study
ORR: Percentage of participants who achieve best overall response Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST).
- CR is defined as disappearance of all target lesions.
- PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: Date of first dose to disease progression or death (Up to 62.4 Months)
Secondary outcomes (23)
Plasma Concentrations of LOXO-292
Outcome data will be provided after the study is completed.
Measured: Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of LOXO-292
Outcome data will be provided after the study is completed.
Measured: Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
Maximum Concentration (Cmax) of LOXO-292
Outcome data will be provided after the study is completed.
Measured: Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
Time to Maximum Concentration (Tmax) of LOXO-292
Outcome data will be provided after the study is completed.
Measured: Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
Recommended LOXO-292 Dose for Phase 2 (MTD)
Outcome data will be provided after the study is completed.
Measured: Cycle 1 (28 days)
To Assess the Preliminary Anti-Tumor Activity of LOXO-292 in Pediatric Participants With Tumors Harboring an Activating RET Alteration as Determined by ORR Based on RECIST v1.1
Outcome data will be provided after the study is completed.
Measured: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Changes From Baseline in Pain Measures as Measured by Wong Baker Faces Scales. Wong-Baker Faces Pain Scale Includes Pictures of Facial Expressions With Correlating Scores of 0 Being 'no Hurt' and 10 Being 'Hurts Worst'.
Outcome data will be provided after the study is completed.
Measured: Up to 24 months
Changes From Baseline in Health Related Quality of Life Measures as Measured by Pediatric Quality of Life (PedsQoL) Inventory Core. PedsQoL Includes a List of Problems With Scores of 0 Being 'Never a Problem' and 4 Being 'Almost Always a Problem'.
Outcome data will be provided after the study is completed.
Measured: Up to 24 months
Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Objective Response Rate as Assessed by RANO, as Assessed by Investigator
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Duration of Response (DOR) as Assessed by Investigator
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Duration of Response (DOR) as Assessed by the IRC
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Progression Free Survival (PFS) as Assessed by Investigator
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
PFS as Assessed by IRC
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Overall Survival (OS)
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Clinical Benefit Rate (by Investigator)
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Clinical Benefit Rate (by IRC)
Outcome data will be provided after the study is completed.
Measured: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed.
Frequency of Adverse Events (AEs)
Outcome data will be provided after the study is completed.
Measured: From the time of informed consent, for approximately 24 months (or earlier if the participants discontinues from the study), and through Safety Follow-up (28 days after the last dose)
To Evaluate the Concordance of Prior Molecular That Detected a RET Alteration Within the Participant's Tumor With Diagnostic Tests Being Evaluated by Sponsor
Outcome data will be provided after the study is completed.
Measured: 6 months
Phase 2: Post-Operative Stage on Participants Treated With LOXO-292
Tumor stage is described according to the Tumor, Node, Metastasis (TNM)Classification of malignant tumors of the Union for International Cancer Control (UICC). Outcome data will be provided after the study is completed.
Measured: Up to 3 years
Phase 2: Surgical Margin Status in Participants Treated With LOXO-292
Tumor margins after surgery are classified into four groups using the International Cancer Control (UICC)-R classification and the Intergroup Rhabdomyosarcoma Staging (IRS) systems: 1) Complete tumor resection with histologically free margins, 2) Macroscopic resection but invaded margins on histology, 3)Macroscopic residual tumor and 4) Distant metastatic tumor. Outcome data will be provided after the study is completed.
Measured: Up to 3 years
Descriptive Analysis of Pretreatment Surgical Plan
Outcome data will be provided after the study is completed.
Measured: Up to 3 years
Descriptive Analysis of Post-Treatment Plans
Outcome data will be provided after the study is completed.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2019
- Study start13 Jun 2019
- Primary completion8 Nov 2024
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Medullary Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Loxo Oncology, Inc.
- Responsible party
- Sponsor
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03899792
- Sponsor's protocol ID
- 17493
- Other IDs
- J2G-OX-JZJJ, LOXO-RET-18036, 2019-000212-28, 2019
- Acronym
- LIBRETTO-121
- Status last verified
- Jan 2026
- First submitted
- 6 Feb 2019
- Last updated
- 6 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Laetsch TW, Kang HJ, Casanova M, Anazodo A, DuBois SG, Manabe A, Navid F, Pappo A, Gilligan AM, Grbovic-Huezo O, Liu D, Suriyapperuma S, Sharma N, Peterson P, Wright J, van Tilburg CM, Morgenstern D. Selpercatinib in Pediatric and Adolescent Patients With RET-Altered Solid Tumors: Safety and Efficacy Results From the Phase I/II LIBRETTO-121 Study. J Clin Oncol. 2026 Oct 14:JCO2503013. doi: 10.1200/JCO-25-03013. Online ahead of print.
PubMed 42874021