Infantile Fibrosarcoma, Infantile Myofibromatosis, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Soft Tissue Sarcoma
Conditions
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
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.
Interventions
DRUGSelpercatinib
Oral LOXO-292
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 21 Years
Healthy volunteers
No
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\[s\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 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 |
| Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Outcome data will be provided after the study is completed. |
| 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) | Outcome data will be provided after the study is completed. |
| Recommended LOXO-292 Dose for Phase 2 (MTD) | Cycle 1 (28 days) | Outcome data will be provided after the study is completed. |
| 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 | 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. |
| 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'. | Up to 24 months | Outcome data will be provided after the study is completed. |
| 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'. | Up to 24 months | Outcome data will be provided after the study is completed. |
| Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator | 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. |
| Objective Response Rate as Assessed by RANO, as Assessed by Investigator | 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. |
| Duration of Response (DOR) as Assessed by Investigator | 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. |
| Duration of Response (DOR) as Assessed by the IRC | 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. |
| 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) | Outcome data will be provided after the study is completed. |
| PFS as Assessed by IRC | 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. |
| Overall Survival (OS) | 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. |
| Clinical Benefit Rate (by Investigator) | 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. |
| Clinical Benefit Rate (by IRC) | 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. |
| Frequency of Adverse Events (AEs) | 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. |
| To Evaluate the Concordance of Prior Molecular That Detected a RET Alteration Within the Participant's Tumor With Diagnostic Tests Being Evaluated by Sponsor | 6 months | Outcome data will be provided after the study is completed. |
| Phase 2: Post-Operative Stage on Participants Treated With LOXO-292 | 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. |
| Phase 2: Surgical Margin Status in Participants Treated With LOXO-292 | 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. |
| Descriptive Analysis of Pretreatment Surgical Plan | Up to 3 years | Outcome data will be provided after the study is completed. |
| Descriptive Analysis of Post-Treatment Plans | Up to 3 years | Outcome data will be provided after the study is completed. |
| Progression Free Survival (PFS) as Assessed by Investigator | 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. |
| 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) | Outcome data will be provided after the study is completed. |
Countries
Australia, Canada, Denmark, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study consisted of two parts: Phase 1 (dose-escalation) and Phase 2 (dose-expansion). In Phase 1, three participants received selpercatinib, with dosing based on body surface area. The starting dose level was 92 mg/m\^2 (maximum 160 mg, twice daily (BID\]), selected to approximate the exposure associated with the recommended Phase 2 dose (RP2D) in adults. The Phase 2 portion opened for enrollment after confirmation of the RP2D of 92 mg/m\^2 (maximum 160 mg BID).
Pre-assignment details
In Phase 2, participants were assigned to one of three disease-based groups: medullary thyroid cancer (MTC), papillary thyroid cancer (PTC), or Other Solid Tumors and received selpercatinib at the RP2D. Current primary results are reported, and additional results will be reported during study completion.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Cohort (Phase 1) Participants received selpercatinib given orally BID, with the dose based on body surface area in a 28-day cycle. The starting dose level of 92mg/m\^2 (maximum160 mg BID) was intended to deliver equivalent exposure to the RP2D in adults. | 3 |
| Cohort 1 (Phase 2): MTC Group Participants in this cohort had MTC and received 92mg/m\^2 (maximum160 mg BID) 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. | 13 |
| Cohort 2 (Phase 2): PTC Group Participants in this cohort had PTC and received 92mg/m\^2 (maximum160 mg BID) 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. | 15 |
| Cohort 3 (Phase 2): Other Cancer Group Participants in this cohort had other (RET-altered non-thyroid) cancer and received 92mg/m\^2 (maximum160 mg BID) 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. | 5 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase 2 | Death | 0 | 0 | 0 | 4 |
| Phase 2 | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Phase 2 | Ongoing Treatment | 0 | 13 | 14 | 2 |
| Phase 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation Cohort (Phase 1) | Cohort 1 (Phase 2): MTC Group | Cohort 2 (Phase 2): PTC Group | Cohort 3 (Phase 2): Other Cancer Group | Total |
|---|---|---|---|---|---|
| Age, Customized Age <=18 years | 2 Participants | 10 Participants | 13 Participants | 5 Participants | 30 Participants |
| Age, Customized Age Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 4 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 11 Participants | 11 Participants | 4 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 7 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 3 Participants | 9 Participants | 6 Participants | 0 Participants | 18 Participants |
| Region of Enrollment Australia | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Canada | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Denmark | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment France | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Germany | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Italy | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Japan | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment South Korea | 0 Participants | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Spain | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Male | 1 Participants | 8 Participants | 8 Participants | 2 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 4 / 6 |
| other Total, other adverse events | 15 / 15 | 15 / 15 | 5 / 6 |
| serious Total, serious adverse events | 8 / 15 | 4 / 15 | 3 / 6 |
Outcome results
Primary
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
Time frame: Cycle 1 (28 Day Cycle)
Population: All participants in Phase 1 of the study who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Cohort (Phase 1) | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
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.
Time frame: Date of first dose to disease progression or death (Up to 62.4 Months)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation Cohort (Phase 1) | Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study | 60.0 Percentage of participants |
| Cohort 2 (Phase 2): PTC Group | Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study | 53.3 Percentage of participants |
| Cohort 3 (Phase 2): Other Cancer Group | Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study | 33.3 Percentage of participants |
Secondary
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.
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)
Secondary
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.
Time frame: Up to 24 months
Secondary
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.
Time frame: Up to 24 months
Secondary
Clinical Benefit Rate (by Investigator)
Outcome data will be provided after the study is completed.
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.
Secondary
Clinical Benefit Rate (by IRC)
Outcome data will be provided after the study is completed.
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.
Secondary
Descriptive Analysis of Post-Treatment Plans
Outcome data will be provided after the study is completed.
Time frame: Up to 3 years
Secondary
Descriptive Analysis of Pretreatment Surgical Plan
Outcome data will be provided after the study is completed.
Time frame: Up to 3 years
Secondary
Duration of Response (DOR) as Assessed by Investigator
Outcome data will be provided after the study is completed.
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.
Secondary
Duration of Response (DOR) as Assessed by the IRC
Outcome data will be provided after the study is completed.
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.
Secondary
Frequency of Adverse Events (AEs)
Outcome data will be provided after the study is completed.
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)
Secondary
Maximum Concentration (Cmax) of LOXO-292
Outcome data will be provided after the study is completed.
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)
Secondary
Objective Response Rate as Assessed by RANO, as Assessed by Investigator
Outcome data will be provided after the study is completed.
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.
Secondary
Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator
Outcome data will be provided after the study is completed.
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.
Secondary
Overall Survival (OS)
Outcome data will be provided after the study is completed.
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.
Secondary
PFS as Assessed by IRC
Outcome data will be provided after the study is completed.
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.
Secondary
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.
Time frame: Up to 3 years
Secondary
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.
Time frame: Up to 3 years
Secondary
Plasma Concentrations of LOXO-292
Outcome data will be provided after the study is completed.
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)
Secondary
Progression Free Survival (PFS) as Assessed by Investigator
Outcome data will be provided after the study is completed.
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.
Secondary
Recommended LOXO-292 Dose for Phase 2 (MTD)
Outcome data will be provided after the study is completed.
Time frame: Cycle 1 (28 days)
Secondary
Time to Maximum Concentration (Tmax) of LOXO-292
Outcome data will be provided after the study is completed.
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)
Secondary
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.
Time frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Secondary
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.
Time frame: 6 months