Trial Outcomes & Findings for Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (NCT NCT03834961)

Last Updated: 2025-12-02

Results Overview

A responder is defined as a patient who achieves a best response of partial response (PR) or complete response (CR) on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2025-12-02

Participant Flow

Zero patients were assigned to Cohort C

Participant milestones

Participant milestones
Measure	Cohort A Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified
Overall Study STARTED	18	15
Overall Study COMPLETED	17	13
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Overall Study Lack of Efficacy	1	1	0
Overall Study Physician Decision	0	1	0

Baseline Characteristics

Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A n=18 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B n=15 Participants Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified	Total n=33 Participants Total of all reporting groups
Age, Categorical <=18 years	18 Participants n=121 Participants	14 Participants n=122 Participants	—	32 Participants n=24 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=121 Participants	1 Participants n=122 Participants	—	1 Participants n=24 Participants
Age, Categorical >=65 years	0 Participants n=121 Participants	0 Participants n=122 Participants	—	0 Participants n=24 Participants
Age, Continuous	0.2 years n=121 Participants	9.4 years n=122 Participants	—	0.7 years n=24 Participants
Sex: Female, Male Female	6 Participants n=121 Participants	8 Participants n=122 Participants	—	14 Participants n=24 Participants
Sex: Female, Male Male	12 Participants n=121 Participants	7 Participants n=122 Participants	—	19 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=121 Participants	1 Participants n=122 Participants	—	5 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=121 Participants	12 Participants n=122 Participants	—	22 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=121 Participants	2 Participants n=122 Participants	—	6 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=121 Participants	0 Participants n=122 Participants	—	0 Participants n=24 Participants
Race (NIH/OMB) Asian	0 Participants n=121 Participants	0 Participants n=122 Participants	—	0 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=121 Participants	0 Participants n=122 Participants	—	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	2 Participants n=121 Participants	3 Participants n=122 Participants	—	5 Participants n=24 Participants
Race (NIH/OMB) White	13 Participants n=121 Participants	10 Participants n=122 Participants	—	23 Participants n=24 Participants
Race (NIH/OMB) More than one race	2 Participants n=121 Participants	0 Participants n=122 Participants	—	2 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=121 Participants	2 Participants n=122 Participants	—	3 Participants n=24 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Cohort A n=18 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Objective Response Rate (ORR) of Children With Infantile Fibrosarcoma (IFS) Treated With Neoadjuvant Larotrectinib Prior to Local Control	94.4 percentage of patients Interval 80.1 to 97.0	—	—

SECONDARY outcome

Timeframe: Up to 1 year

The Kaplan-Meier method will be used to estimate 1-year EFS, defined as the time from study entry until last contact, relapse, secondary malignancy, or death.

Outcome measures

Outcome measures
Measure	Cohort A n=18 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Event-free Survival (EFS) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	94.4 percentage of patients Interval 66.6 to 99.2	—	—

SECONDARY outcome

Timeframe: Up to 1 year

The Kaplan-Meier method will be used to estimate 1-year OS, defined as the time from study entry until last contact or death.

Outcome measures

Outcome measures
Measure	Cohort A n=18 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Overall Survival (OS) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	100 percentage of patients Interval 100.0 to 100.0	—	—

SECONDARY outcome

Timeframe: Up to 5 years

Will be defined among patients with a confirmed best response of either PR and CR. Will be computed as the time from first observation of either PR or CR until either the first observation of progressive disease (PD) (event) or last known observation of the patient (censored observation).

Outcome measures

Outcome measures
Measure	Cohort A n=17 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Duration of Response (DoR) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	2.1 years Interval 0.4 to 4.2	—	—

SECONDARY outcome

Timeframe: Up to 5 years

A responder is defined as a patient who achieves a best response of PR or CR on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.

Outcome measures

Outcome measures
Measure	Cohort A n=15 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
ORR of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	60 percentage of patients Interval 32.3 to 83.7	—	—

SECONDARY outcome

Timeframe: Up to 1 year

The Kaplan-Meier method will be used to estimate 1-year EFS, defined as the time from study entry until last contact, relapse, secondary malignancy, or death.

Outcome measures

Outcome measures
Measure	Cohort A n=15 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
EFS of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	93.3 percentage of participants Interval 61.3 to 99.0	—	—

SECONDARY outcome

Timeframe: Up to 1 year

The Kaplan-Meier method will be used to estimate 1-year OS, defined as the time from study entry until last contact or death.

Outcome measures

Outcome measures
Measure	Cohort A n=15 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
OS of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	93.3 percentage of patients Interval 61.3 to 99.0	—	—

SECONDARY outcome

Timeframe: Up to 5 years

Will be defined among patients with a confirmed best response of either PR and CR. Will be computed as the time from first observation of either PR or CR until either the first observation of PD (event) or last known observation of the patient (censored observation).

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
DoR of Children With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control	2.9 years Interval 0.2 to 4.8	—	—

SECONDARY outcome

Timeframe: Through 30 days after treatment, a mean of 12.6 months

Population: Zero patients were assigned to Cohort C

Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy. Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Outcome measures

Outcome measures
Measure	Cohort A n=18 Participants Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B n=15 Participants Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Percentage of Participants With Adverse Events	44.4 percentage of patients Interval 21.5 to 69.2	20 percentage of patients Interval 4.3 to 48.1	—

SECONDARY outcome

Timeframe: Up to 5 years

The percentage of ctDNA and frequency with which patients have detectable ctDNA prior to the start of therapy and at times during therapy when subsequent serial samples are obtained (2 weeks, 4 weeks, 24 weeks of treatment, at the time of discontinuation of larotrectinib therapy, and at progression) will be calculated.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A

Serious events: 3 serious events

Other events: 9 other events

Deaths: 1 deaths

Cohort B

Serious events: 1 serious events

Other events: 5 other events

Deaths: 1 deaths

Cohort C

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A n=18 participants at risk Patients with infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort B n=15 participants at risk Patients with solid tumors including CNS tumors, with an NTRK1, NTRK2, or NTRK3 fusion identified	Cohort C Patients with a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified
Eye disorders Optic nerve disorder	0.00% 0/18 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	6.7% 1/15 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	— 0/0 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Gastrointestinal disorders Constipation	5.6% 1/18 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	0.00% 0/15 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	— 0/0 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Infections and infestations Sepsis	5.6% 1/18 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	0.00% 0/15 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	— 0/0 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Investigations Aspartate aminotransferase increased	5.6% 1/18 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	0.00% 0/15 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	— 0/0 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Psychiatric disorders Irritability	5.6% 1/18 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	0.00% 0/15 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.	— 0/0 • Through 30 days after treatment, a mean of 12.6 months Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 6262411500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior sponsor approval
Publication restrictions are in place

Restriction type: OTHER