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Carcinoma, Non-Small-Cell Lung

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Merestinib at the recommended phase II dose of 120 mg by mouth daily.

Merestinib is a potent and selective type II MET/RON kinase inhibitor with the ability to achieve inhibition of MET activity both in vitro and in vivo.

Merestinib

Mark Awad, MD

This research study is examining merestinib (a targeted therapy) as a possible treatment for non-small cell lung cancer (NSCLC) that was found to have a specific change in the MET gene (a MET exon 14 mutation); or as a treatment for solid tumors that have an alteration in the NTRK gene (an NTRK1, 2, or 3 rearrangement).

This is an open-label, phase II study of merestinib in patients with advanced NSCLC with a MET exon 14 mutation or patients with advanced cancer harboring an NTRK1, 2, or 3 rearrangement. Twenty patients with a MET mutation will be evaluated in a single-arm design. A small separate cohort of 5 NTRK patients will be evaluated for exploratory purposes.

Merestinib (LY2801653) is a small molecule that has been shown in vitro to be a reversible type II ATP-competitive inhibitor of MET. Pre-clinical testing also has shown merestinib to inhibit several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, NTRK1/2/3, and DDR1/2 and the serine/threonine kinases MKNK1/2.

Merestinib In Non-Small Cell Lung Cancer And Solid Tumors

A Phase II Study of Merestinib in Non-Small Cell Lung Cancers Harboring MET Exon 14 Mutations and Solid Tumors With NTRK Rearrangements

ORR was defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment in MET Exon 14 Cohort based on RECISTv1.1 criteria.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

PFS based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) defined per RECIST 1.1 criteria. or death, or is censored at time of last disease assessment.

DOR, estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per RECISTv1.1, until the first date that recurrent or progressive disease is objectively documented. Patients without PD are censored at the date of last disease assessment.

All grade 4-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.

Eli Lilly and Company

Dana-Farber Cancer Institute

Principal Investigator

Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Merestinib: Oral, predetermined dosage of 120mg per protocol, once daily per 28 day treatment cycle

NSCLC (Met Exon 14 Mutation)

Solid Tumor (NTRK1,2,3 Rearrangement)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

No patient was accrued in the solid tumor arm.

Mark Awad, MD, PhD

The analysis population is comprised of eligible and treated patients.

Overall Response Rate (ORR) - MET Exon 14 Cohort

Median Overall Survival (OS) - MET Exon 14 Cohort

The analysis population is comprised of all eligible and treated patients.

Median Progression-free Survival (PFS) - MET Exon 14 Cohort

This analysis dataset is comprised of all patients who had a CR or PR on treatment.

Median Duration of Response (DOR) - MET Exon 14 Cohort

This analysis dataset is comprised of all eligible and treated patients.

Grade 4-5 Treatment-related Toxicity Rate

Merestinib: Oral, predetermined dosage of 120 mg per protocol, once daily per 28 day treatment cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Merestinib In Non-Small Cell Lung Cancer And Solid Tumors	NCT02920996	Carcinoma, Non-... Solid Tumor	Merestinib	18 Years -	Dana-Farber Cancer Institute
Merestinib In Non-Small Cell Lung Cancer And Solid Tumors	NCT02920996	Carcinoma, Non-... Solid Tumor	Merestinib	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for ntrk rearrangement