Clinical trial NCT06390852: Testing LOXO-101 as Potentially Targeted Treatment in Cancers With NTRK Genetic Changes (MATCH - Subprotocol Z1E)
Official title: MATCH Treatment Subprotocol Z1E: Larotrectinib (LOXO-101) in Patients With Tumors With NTRK Fusions
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Lymphoma
Advanced Malignant Solid Neoplasm
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Multiple Myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2024-04-30
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
measure: 6-month progression free survival (PFS)
timeFrame: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
measure: Progression free survival
timeFrame: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: ECOG-ACRIN Cancer Research Group
state: Pennsylvania
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: David S Hong
role: PRINCIPAL_INVESTIGATOR
References: