A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors (LIBRETTO-121)

January 2, 2026 updated by: Eli Lilly and Company

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2
  • Phase 1

Expanded Access

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • The Children's Hospital at Westmead
    • Victoria
      • Melbourne, Victoria, Australia, 3052
        • Royal Children's Hospital
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children
  • Denmark
      • Copenhagen, Denmark, 2200
        • Rigshospitalet
  • France
      • Villejuif, France, 94805
        • Gustave Roussy
  • Germany
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69115
        • Universitätsklinikum Heidelberg
  • Italy
    • Lombardy
      • Milan, Lombardy, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Japan
      • Hiroshima, Japan, 734-8551
        • Hiroshima University Hospital
      • Kyoto, Japan, 606-8507
        • Kyoto University Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Hokkaido University Hospital
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
  • South Korea
    • Korea
      • Seoul, Korea, South Korea, 03080
        • Seoul National University Hospital
  • Spain
    • Barcelona [Barcelona]
      • Barcelona, Barcelona [Barcelona], Spain, 8035
        • Hospital Universitari Vall d'Hebron
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, NW1 2BU
        • University College Hospital - London
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital of Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • The Children's Hospital for Cancer and Blood Disorders
    • Florida
      • Orlando, Florida, United States, 32827
        • Nemours Children's Health
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Hospital
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • University of Texas Southwestern Medical Center at Dallas
      • Houston, Texas, United States, 77025
        • Texas Childrens Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital Research Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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])

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: Medullary Thyroid Cancer (MTC) Group

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.
Drug: Selpercatinib
Oral LOXO-292
Other Names:
  • LOXO-292
  • LY3527723
Experimental: Cohort 2: Papillary Thyroid Cancer (PTC) Group

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.
Drug: Selpercatinib
Oral LOXO-292
Other Names:
  • LOXO-292
  • LY3527723
Experimental: Cohort 3: Other Cancer Group

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.
Drug: Selpercatinib
Oral LOXO-292
Other Names:
  • LOXO-292
  • LY3527723

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (28 Day Cycle)

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
Cycle 1 (28 Day Cycle)
Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study
Time Frame: Date of first dose to disease progression or death (Up to 62.4 Months)

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.
Date of first dose to disease progression or death (Up to 62.4 Months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma Concentrations of LOXO-292
Time Frame: 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)
Outcome data will be provided after the study is completed.
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
Time Frame: 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)
Outcome data will be provided after the study is completed.
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
Time Frame: 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)
Outcome data will be provided after the study is completed.
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
Time Frame: 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)
Outcome data will be provided after the study is completed.
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)
Time Frame: Cycle 1 (28 days)
Outcome data will be provided after the study is completed.
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
Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Outcome data will be provided after the study is completed.
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'.
Time Frame: Up to 24 months
Outcome data will be provided after the study is completed.
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'.
Time Frame: Up to 24 months
Outcome data will be provided after the study is completed.
Up to 24 months
Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator
Time Frame: 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.
Outcome data will be provided after the study is completed.
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
Time Frame: 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.
Outcome data will be provided after the study is completed.
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
Time Frame: 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.
Outcome data will be provided after the study is completed.
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
Time Frame: 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.
Outcome data will be provided after the study is completed.
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
Time Frame: 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.
Outcome data will be provided after the study is completed.
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
Time Frame: 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.
Outcome data will be provided after the study is completed.
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)
Time Frame: 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.
Outcome data will be provided after the study is completed.
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)
Time Frame: 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.
Outcome data will be provided after the study is completed.
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)
Time Frame: 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.
Outcome data will be provided after the study is completed.
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)
Time Frame: 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)
Outcome data will be provided after the study is completed.
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
Time Frame: 6 months
Outcome data will be provided after the study is completed.
6 months
Phase 2: Post-Operative Stage on Participants Treated With LOXO-292
Time Frame: Up to 3 years
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.
Up to 3 years
Phase 2: Surgical Margin Status in Participants Treated With LOXO-292
Time Frame: Up to 3 years
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.
Up to 3 years
Descriptive Analysis of Pretreatment Surgical Plan
Time Frame: Up to 3 years
Outcome data will be provided after the study is completed.
Up to 3 years
Descriptive Analysis of Post-Treatment Plans
Time Frame: Up to 3 years
Outcome data will be provided after the study is completed.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Collaborators

Loxo Oncology, Inc.

Investigators

  • Study Director: 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), Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2019

Primary Completion (Actual)

November 8, 2024

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

February 6, 2019

First Submitted That Met QC Criteria

April 1, 2019

First Posted (Actual)

April 2, 2019

Study Record Updates

Last Update Posted (Estimated)

January 6, 2026

Last Update Submitted That Met QC Criteria

January 2, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17493
  • J2G-OX-JZJJ (Other Identifier: Eli Lilly and Company)
  • LOXO-RET-18036 (Other Identifier: LOXO Oncology, Inc.)
  • 2019-000212-28 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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