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

March 6, 2024 updated by: Loxo Oncology, Inc.

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

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 (Estimated)

50

Phase

  • Phase 2
  • Phase 1

Expanded Access

Available outside the clinical trial. 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 Contact

  • Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: clinicaltrials.gov@lilly.com

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • The Children's Hospital at Westmead
        • Contact:
          • Phone Number: 61293821730
        • Principal Investigator:
          • David Ziegler
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Recruiting
        • Royal Children's Hospital
        • Contact:
          • Phone Number: + 61 3 93459180
        • Principal Investigator:
          • Martin Campbell
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • The Hospital For Sick Children
        • Principal Investigator:
          • Daniel Alexander Morgenstern
        • Contact:
          • Phone Number: 416.813.7654
  • Denmark
      • Copenhagen, Denmark, 2200
        • Recruiting
        • Rigshospitalet
        • Contact:
          • Phone Number: 4535453545
        • Principal Investigator:
          • Karstend Nysom
  • France
      • Villejuif Cedex, France, 94805
        • Recruiting
        • Gustave Roussy
        • Contact:
          • Phone Number: +33 1.42.11.46.61
        • Principal Investigator:
          • Charlotte Rigaud
  • Germany
    • Baden-Württemberg
      • Heidelberg, Baden-Württemberg, Germany, 69120
        • Recruiting
        • Universitätsklinikum Heidelberg
        • Contact:
          • Phone Number: +49 6221 56-36926
        • Principal Investigator:
          • Cornelis Van Tilburg
  • Italy
    • Lombardia
      • Milan, Lombardia, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori
        • Contact:
          • Phone Number: +390223902588
        • Principal Investigator:
          • Michela Casanova
  • Japan
      • Hiroshima, Japan, 734-8551
        • Recruiting
        • Hiroshima University Hospital
        • Contact:
          • Phone Number: 81822575555
        • Principal Investigator:
          • Shuhei Karakawa
      • Kyoto, Japan, 606-8507
        • Recruiting
        • Kyoto University Hospital
        • Contact:
          • Phone Number: 81757513111
        • Principal Investigator:
          • Katsutsugu Umeda
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Recruiting
        • Hokkaido University Hospital
        • Contact:
          • Phone Number: 81 117161161
        • Principal Investigator:
          • Atushi Manabe
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
          • Phone Number: 81335422511
        • Principal Investigator:
          • Ayumu Arakawa
  • Korea, Republic of
    • Seoul, Korea
      • Seoul, Seoul, Korea, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Phone Number: 82-2-2072-3304
        • Principal Investigator:
          • HyoungJin Kang
  • Spain
    • Barcelona [Barcelona]
      • Barcelona, Barcelona [Barcelona], Spain, 8035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
          • Phone Number: 934893000
        • Principal Investigator:
          • Raquel Hladun
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, NW1 2BU
        • Recruiting
        • University College Hospital - London
        • Principal Investigator:
          • Sara Stoneham
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Childrens Hospital of Los Angeles
        • Principal Investigator:
          • Leo Mascarenhas
        • Contact:
          • Phone Number: 323-669-2101
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Not yet recruiting
        • The Children's Hospital for Cancer and Blood Disorders
        • Contact:
          • Phone Number: 720-777-6458
        • Principal Investigator:
          • Margaret Macy
    • Florida
      • Orlando, Florida, United States, 32827
        • Not yet recruiting
        • Nemours Children's Health
        • Principal Investigator:
          • Ramamoorthy Nagasubramanian
        • Contact:
          • Phone Number: +91 407567 4000
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Steven DuBois
        • Contact:
          • Phone Number: 617-632-5869
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • Recruiting
        • University of Minnesota Hospital
        • Principal Investigator:
          • Emily Greengard
        • Contact:
          • Phone Number: 612-273-9820
    • New York
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Phone Number: 212-639-6729
        • Principal Investigator:
          • Julia Glade Bender
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Not yet recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
          • Phone Number: 513-636-7329
        • Principal Investigator:
          • Brian Turpin
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
          • Phone Number: 267-426-9338
        • Principal Investigator:
          • frank balis
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Recruiting
        • St. Jude Children's Research Hospital
        • Contact:
          • Phone Number: 901-595-2813
        • Principal Investigator:
          • Alberto Pappo
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • Recruiting
        • University of Texas Southwestern Medical Center at Dallas
        • Principal Investigator:
          • Tanya Watt
        • Contact:
          • Phone Number: 214-456-6363
      • Houston, Texas, United States, 77025
        • Recruiting
        • Texas Childrens Hospital
        • Principal Investigator:
          • Stephanie Fetzko
        • Contact:
          • Phone Number: 713-770-3453
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital Research Foundation
        • Contact:
          • Phone Number: 206-987-2114
        • Principal Investigator:
          • Douglas Hawkins

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LOXO-292
Phase 1- Dose Escalation and determination of MTD; multiple dose levels of LOXO-292 to be evaluated; Phase 2 - The MTD/recommended dose from Phase 1
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumors: Dose Limiting Toxicities (DLTs)
Time Frame: During the first 28-day cycle of LOXO-292 treatment
For Phase 1
During the first 28-day cycle of LOXO-292 treatment
To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumors: DLTs
Time Frame: During the first 28-day cycle of LOXO-292 treatment
For Phase 1
During the first 28-day cycle of LOXO-292 treatment
Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC)
Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
For Phase 2
Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC
Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
For Phase 2
Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 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)
Phase 1
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)
Phase 1 and Phase 2
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)
Phase 1 and Phase 2
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)
Phase 1 and Phase 2
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)
For Phase 1
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)
For Phase 1
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
For Phase 1
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
For Phase 1
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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.
For Phase 2
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)
For Phase 2
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
For Phase 2
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)
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.
Up to 3 years
Descriptive Analysis of Pretreatment Surgical Plan
Time Frame: Up to 3 years
For Phase 2
Up to 3 years
Descriptive Analysis of Post-Treatment Plans
Time Frame: Up to 3 years
For Phase 2
Up to 3 years

Collaborators and Investigators

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

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 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 (Estimated)

December 15, 2024

Study Completion (Estimated)

May 31, 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 (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 6, 2024

Last Verified

March 1, 2024

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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