Merestinib In Non-Small Cell Lung Cancer And Solid Tumors

NCT02920996 | Terminated Phase 2 Results DMC

• 2 other identifiers: 16-374I30-MC-E001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Carcinoma, Non-Small-Cell Lung; Solid Tumor

Keywords

NSCLC; MET; Non-small cell lung cancer; MET mutation; NTRK rearrangement; NTRK; targeted therapy; MET exon 14; NTRK1; NTRK2; NTRK3; merestinib; LY2801653

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) - MET Exon 14 Cohort

  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.

  ORR evaluation starting at cycle 2 day 28 and at the end of every 2 cycles of treatment thereafter. The median treatment duration is 1.20 months with range (0.26 months - 28.81 months).

Secondary Outcomes (4)

• Median Overall Survival (OS) - MET Exon 14 Cohort

  Survival data collection in long-term follow-up every 3 months. Median follow-up for survival is of 24.28 months with range (0.46 months - 32.13 months).

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

  Disease was evaluated at cycle 2 day 28 and at the end of every 2 cycles thereafter and in long-term survival followed-up every 3 months. Median follow-up for survival is of 24.28 months with range (0.46 months - 32.13 months).

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

  Radiologic evaluation starting at cycle 2 day 28 and at the end of every 2 cycles of treatment thereafter. The median of treatment duration is 1.20 months with range (0.26 months - 28.81 months).

• Grade 4-5 Treatment-related Toxicity Rate

  AE evaluated on treatment on day 1 and 15 on cycle 1, and day 1 on each cycle thereafter. The median of treatment duration is 1.20 months with range (0.26 months - 28.81 months).

Study Arms (2)

NSCLC (Met Exon 14 Mutation)

EXPERIMENTAL

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

Drug: Merestinib

Solid Tumor (NTRK1,2,3 Rearrangement)

EXPERIMENTAL

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

Drug: Merestinib

Interventions

Merestinib DRUG

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.

Also known as: LY2801653

NSCLC (Met Exon 14 Mutation); Solid Tumor (NTRK1,2,3 Rearrangement)

Eligibility Criteria

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

You may qualify if:

• Baseline evaluations are to be conducted within 14 days prior to start of protocol therapy, with the exception of the informed consent and baseline tumor imaging which may be obtained up to 28 days prior to the start of protocol therapy.
• For enrollment into the MET cohort: Participants must have a histologically or cytologically confirmed advanced NSCLC and must have received at least one prior line of therapy in the metastatic setting.
• For enrollment into the NTRK cohort: Participants must have a histologically or cytologically confirmed advanced solid tumor and must have received at least one prior line of therapy in the metastatic setting.
• Participants enrolling into the MET cohort must have a MET exon 14 mutation as confirmed by targeted NextGen Sequencing using the DFCI/BWH OncoPanel or another CLIA-certified method. Participants whose NSCLC specimens contain actionable genetic mutations/alterations (e.g. ALK/EGFR) should receive appropriate targeted therapies prior to enrollment in the trial.
• Participants enrolling into the NTRK cohort must have an NTRK1, 2, or 3 rearrangement as confirmed by targeted NextGen Sequencing using the DFCI/BWH OncoPanel or another CLIA-certified method.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Participants enrolling to the MET cohort who have received treatment with a prior MET inhibitor must be able and willing to undergo a baseline tumor biopsy.
• Participants enrolling to the NTRK cohort who have received treatment with a prior NTRK inhibitor must be able and willing to undergo a baseline tumor biopsy.
• Age ≥ 18 years. As no dosing or adverse event data are currently available in participants \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
• ECOG performance status ≤ 1 (see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 K/uL
• Platelets ≥ 100 K/uL
• Hemoglobin ≥ 9 g/dL (with or without transfusion support)
• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

You may not qualify if:

• Participants who have had chemotherapy, immune therapy, other investigational therapy, major surgery, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Participants who have not recovered to eligibility levels from adverse events due to agents administered more than 3 weeks earlier.
• Participants who are receiving any other investigational agents.
• Participants with untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with a history of brain metastases that have been treated, are no longer taking corticosteroids, and have been stable on imaging for ≥ 4 weeks following the last date of treatment are permitted. Note: a brain MRI is required during the screening period.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to merestinib.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because merestinib is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with merestinib, breastfeeding should be discontinued if the mother is treated with merestinib.
• Known HIV-positive participants are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Participants enrolling to the MET cohort who have received a prior MET inhibitor may not be on anticoagulant therapy unless the investigator has deemed it safe to temporarily hold to facilitate the baseline tumor biopsy.
• Participants enrolling to the NTRK cohort who have received a prior NTRK inhibitor may not be on anticoagulant therapy unless the investigator has deemed it safe to temporarily hold to facilitate the baseline tumor biopsy.
• Participants with uncontrolled high blood pressure, defined as a blood pressure during screening of ≥ 160/100 despite medical management.
• Participants must not have any clinically significant gastrointestinal abnormalities that in the opinion of the treating investigator may alter absorption of oral medications, such as malabsorption syndrome or major resection of the stomach or bowels.
• Participants with a history of a second primary malignancy. Exceptions include: patients with a history of malignancies that were treated curatively and have not recurred within 3 years prior to study entry; resected basal and squamous cell carcinomas of the skin, and completely resected carcinoma in situ of any type.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Yan SB, Um SL, Peek VL, Stephens JR, Zeng W, Konicek BW, Liu L, Manro JR, Wacheck V, Walgren RA. MET-targeting antibody (emibetuzumab) and kinase inhibitor (merestinib) as single agent or in combination in a cancer model bearing MET exon 14 skipping. Invest New Drugs. 2018 Aug;36(4):536-544. doi: 10.1007/s10637-017-0545-x. Epub 2017 Nov 29.

  PMID: 29188469 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

merestinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Mark Awad, MD, PhD
• Organization: Dana-Farber Cancer Institute

mark_awad@dfci.harvard.edu

(617) 632-3468

Study Officials

• Mark Awad, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2016
• First Posted: September 30, 2016
• Study Start: November 11, 2016
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2023
• Last Updated: April 11, 2024
• Results First Posted: April 11, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)