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

NCT03899792 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: 17493J2G-OX-JZJJLOXO-RET-180362019-000212-28
• Study Type: interventional
• Target: 36
• Locations: 11 countries
• Sites: 26

Brief 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.

Conditions

Medullary Thyroid Cancer; Infantile Myofibromatosis; Infantile Fibrosarcoma; Papillary Thyroid Cancer; Soft Tissue Sarcoma

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; RET-PTC6; TRIM27-RET; TRIM33-RET; RET-PTC7; AKAP13-RET; FKBP15-RET; SPECC1L-RET; TBL1XR1-RET; BCR-RET; FGRF1OP-RET; RFG8-RET; RET-PTC9; ACBD5-RET; MYH13-RET; CUX1-RET; KIAA1468-RET; FRMD4A-RET; SQSTM1-RET; AFAP1L2-RET; PPFIBP2-RET; EML4-RET; PARD3-RET; G533C; C609F; C609G; C609R; C609S; C609Y; C611F; C611G; C611S; C611Y; C611W; C618F; C618R; C618S; C620F; C620R; C620S; C630R; C630Y; D631Y; C634F; C634G; C634R; C634S; C634W; C634Y; K666E; E768D; L790F; V804L; V804M; A883F; S891A; R912P; CLIP1-RET; Y806C; RET fusion; RET alteration; RET mutation; RET rearrangement; RET translocation; Neoplasms by Site; Neoplasms; Non-Small Cell Lung Cancer; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Respiratory Tract Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Medullary Thyroid Cancer; Papillary Thyroid Cancer; Thyroid Diseases; Thyroid Neoplasms; Cancer of the Thyroid; Cancer of Thyroid; Neoplasms, Thyroid; Thyroid Adenoma; Thyroid Cancer; Thyroid Carcinoma; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thoracic Neoplasms; CNS tumor; Primary CNS tumor; Colonic Neoplasms; Cancer of Colon; Cancer of the Colon; Colon Cancer; Colon Neoplasms; Colonic Cancer; Neoplasms, Colonic; Malignant tumor of Breast; Mammary Cancer; Mammary Carcinoma, Human; Mammary Neoplasm, Human; Neoplasms, Breast; Tumors, Breast; Human Mammary Carcinoma; Malignant Neoplasm of Breast; Breast Carcinoma; Breast Tumors; Cancer of the Breast; Breast Neoplasms; Breast Cancer; RET Inhibitor; MTC; NSCLC; Soft tissue sarcoma; Infantile Myofibromatosis; Infantile Fibrosarcoma

Outcome Measures

Primary Outcomes (2)

• 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

  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.

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

Secondary Outcomes (23)

• Plasma Concentrations of LOXO-292

  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

  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

  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

  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)

  Cycle 1 (28 days)

Study Arms (3)

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.

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.

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.

Drug: Selpercatinib

Interventions

Selpercatinib DRUG

Oral LOXO-292

Also known as: LOXO-292, LY3527723

Cohort 1: Medullary Thyroid Cancer (MTC) Group; Cohort 2: Papillary Thyroid Cancer (PTC) Group; Cohort 3: Other Cancer Group

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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\[s\])

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (26)

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

The Children's Hospital for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

Nemours Children's Health

Orlando, Florida, 32827, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota Hospital

Minneapolis, Minnesota, 55455, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390-9063, United States

Location

Texas Childrens Hospital

Houston, Texas, 77025, United States

Location

Seattle Children's Hospital Research Foundation

Seattle, Washington, 98105, United States

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Rigshospitalet

Copenhagen, 2200, Denmark

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69115, Germany

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Seoul National University Hospital

Seoul, Korea, 03080, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona], 8035, Spain

Location

University College Hospital - London

London, Greater London, NW1 2BU, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Medullary; Myofibromatosis; Thyroid Cancer, Papillary; Sarcoma; Neoplasms by Site; Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thoracic Neoplasms; Central Nervous System Neoplasms; Colonic Neoplasms; Breast Neoplasms

Interventions

selpercatinib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Adenocarcinoma, Papillary; Bronchial Diseases; Nervous System Neoplasms; Nervous System Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: April 2, 2019
• Study Start: June 13, 2019
• Primary Completion: November 8, 2024
• Study Completion (Estimated): May 1, 2029
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); IT (1); US (12); DE (1); DK (1); CA (1); FR (1); GB (1); AU (2); JP (4); KR (1)