Testing LOXO-101 as Potentially Targeted Treatment in Cancers With NTRK Genetic Changes (MATCH - Subprotocol Z1E)

NCT ID: NCT06390852

Last Updated: 2025-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-12

Study Completion Date

2026-12-31

Brief Summary

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This phase II MATCH treatment trial tests how well larotrectinib (LOXO-101) works in treating patients with cancer that has certain genetic changes. Larotrectinib (LOXO-101) is used in patients whose cancer has a mutated (changed) form of a gene called NTRK. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive larotrectinib (LOXO-101) orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Conditions

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Advanced Lymphoma Advanced Malignant Solid Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (larotrectinib [LOXO-101])

Patients receive larotrectinib (LOXO-101) PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Larotrectinib

Intervention Type DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Larotrectinib

Given PO

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography ARRY 470 LOXO 101 LOXO-101 LOXO101 Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI

Eligibility Criteria

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Inclusion Criteria

* Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
* Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
* Patients must have a malignancy harboring an NTRK1, NTRK2 or NTRK3 gene fusion, as determined by the MATCH screening assessment
* Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
* Patients must not have known hypersensitivity to larotrectinib (LOXO-101) or compounds of similar chemical or biologic composition
* Patients with inability to discontinue treatment with a strong CYP3A4 inhibitor or inducer prior to start of treatment are excluded
* Patients who have previously received treatment with a TRKA, TRKB, or TRKC inhibitor are excluded. Such inhibitors include larotrectinib (LOXO-101), entrectinib (RXDX-101), TSR-011, DS6051, altiratinib (DCC-2701), MGCD516, dovitinib (TKI258, CHIR528), AZD7451, PLX7486, and BIBF1120
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David S Hong

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2024-01138

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-Z1E

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-Z1E

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01138

Identifier Type: -

Identifier Source: org_study_id

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