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

NCT06390852 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2024-01138EAY131-Z1EU10CA180820
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Secondary Outcomes (2)

• 6-month Progression Free Survival (PFS)

  Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined

• Progression Free Survival

  Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Study Arms (1)

Treatment (larotrectinib [LOXO-101])

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Larotrectinib; Procedure: Magnetic Resonance Imaging

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (larotrectinib [LOXO-101])

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (larotrectinib [LOXO-101])

Larotrectinib DRUG

Given PO

Also known as: ARRY 470, LOXO 101, LOXO-101, LOXO101

Treatment (larotrectinib [LOXO-101])

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: 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

Treatment (larotrectinib [LOXO-101])

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: 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

Treatment (larotrectinib [LOXO-101])

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma

Interventions

Biopsy; Specimen Handling; larotrectinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Cancer Research Group

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• David S Hong

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2024
• First Posted: April 30, 2024
• Study Start: August 21, 2017
• Primary Completion: April 24, 2023
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 1, 2026
• Results First Posted: August 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)