TriangleNCT03899792 · CITED IN SOURCE DOCUMENTS
A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1, PHASE2
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-01-06
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study
Plasma Concentrations of LOXO-292
Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of LOXO-292
Maximum Concentration (Cmax) of LOXO-292
Time to Maximum Concentration (Tmax) of LOXO-292
Recommended LOXO-292 Dose for Phase 2 (MTD)
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
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'.
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'.
Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator
Objective Response Rate as Assessed by RANO, as Assessed by Investigator
Duration of Response (DOR) as Assessed by Investigator
Duration of Response (DOR) as Assessed by the IRC
Progression Free Survival (PFS) as Assessed by Investigator
PFS as Assessed by IRC
Overall Survival (OS)
Clinical Benefit Rate (by Investigator)
Clinical Benefit Rate (by IRC)
Frequency of Adverse Events (AEs)
To Evaluate the Concordance of Prior Molecular That Detected a RET Alteration Within the Participant's Tumor With Diagnostic Tests Being Evaluated by Sponsor
Phase 2: Post-Operative Stage on Participants Treated With LOXO-292
Phase 2: Surgical Margin Status in Participants Treated With LOXO-292
Descriptive Analysis of Pretreatment Surgical Plan
Descriptive Analysis of Post-Treatment Plans
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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\[s\])
- healthy Volunteers
- false
- maximum Age
- 21 Years
- minimum Age
- 6 Months
- sex
- ALL
- std Ages
- CHILD
- ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Drug: Selpercatinib
- label
- Cohort 1: Medullary Thyroid Cancer (MTC) Group
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Selpercatinib
- label
- Cohort 2: Papillary Thyroid Cancer (PTC) Group
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Selpercatinib
- label
- Cohort 3: Other Cancer Group
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Cohort 1: Medullary Thyroid Cancer (MTC) Group
- Cohort 2: Papillary Thyroid Cancer (PTC) Group
- Cohort 3: Other Cancer Group
- description
- Oral LOXO-292
- name
- Selpercatinib
- other Names
- LOXO-292
- LY3527723
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 36
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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
- measure
- Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
- time Frame
- Cycle 1 (28 Day Cycle)
- description
- 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.
- measure
- 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)
- secondary Outcomes
- description
- Outcome data will be provided after the study is completed.
- measure
- 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)
- description
- Outcome data will be provided after the study is completed.
- measure
- 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)
- description
- Outcome data will be provided after the study is completed.
- measure
- 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)
- description
- Outcome data will be provided after the study is completed.
- measure
- 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)
- description
- Outcome data will be provided after the study is completed.
- measure
- Recommended LOXO-292 Dose for Phase 2 (MTD)
- time Frame
- Cycle 1 (28 days)
- description
- Outcome data will be provided after the study is completed.
- measure
- 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)
- description
- Outcome data will be provided after the study is completed.
- measure
- 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
- description
- Outcome data will be provided after the study is completed.
- measure
- 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
- description
- Outcome data will be provided after the study is completed.
- measure
- 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.
- description
- Outcome data will be provided after the study is completed.
- measure
- 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.
- description
- Outcome data will be provided after the study is completed.
- measure
- 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.
- description
- Outcome data will be provided after the study is completed.
- measure
- 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.
Full study description
- 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.
- 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.
Source references
Source notices and limitations
Discovery and provenance
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- pediatric and young adult patients with advanced RET -activated solid tumors enrolled in a multicenter, open-label, multi-cohort clinical trial (LIBRETTO-121 , NCT03899792). Patients received RETEVMO 92 mg/m 2 orally twice daily until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. Tumor
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- pediatric and young adult patients with advanced RET -activated solid tumors enrolled in a multicenter, open-label, multi-cohort clinical trial (LIBRETTO-121 , NCT03899792) [see Clinical Studies ( 14.2 )]. Efficacy was evaluated in 15 patients with RET fusion-positive thyroid cancer who were non-responsive to available therapies
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- pediatric and young adult patients with advanced RET- activated solid tumors enrolled in a multicenter, open-label, multi-cohort clinical trial (LIBRETTO-121 , NCT03899792) [see Clinical Studies ( 14.2 )]. Efficacy was evaluated in 3 patients with locally advanced refractory RET -fusion positive other solid tumors who were unresp
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- inoid, ovarian, small intestine, and neuroendocrine (including pancreatic).</p><p>Efficacy in pediatric and young adult patients was evaluated in LIBRETTO-121 (NCT03899792), a multicenter, open-label, multi-cohort trial. Efficacy was evaluated in patients with locally advanced refractory <em>RET</em> fusion-positive solid tumors
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Preserved source evidence · Not medical advice