Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

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

Overall Study

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Neoplasm Metastasis

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Ramucirumab

Antimetabolites

Angiogenesis Inhibitors

Growth Inhibitors

Participants received 8 mg/kg ramucirumab plus 25 mg/square meter (mg/m²) cisplatin and 1000 mg/m² gemcitabine intravenously (IV) on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).

Participants received placebo (indistinguishable and equivalent volume to ramucirumab) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Participants received 80 mg merestinib orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for merestinib therapy).

Participants received placebo (indistinguishable to merestinib) orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days. Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Placebo Oral

Placebo IV

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to evaluate the efficacy and safety of ramucirumab or merestinib or placebo plus cisplatin and gemcitabine in participants with advanced or metastatic biliary tract cancer.

A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer

Randomized, Double-Blind, Phase 2 Study of Ramucirumab or Merestinib or Placebo Plus Cisplatin and Gemcitabine as First-Line Treatment in Patients With Advanced or Metastatic Biliary Tract Cancer

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

OS defined as the time from from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

ORR was the number of participants who achieve a best overall response of CR or PR divided by the total number of participants randomized to the corresponding treatment arm as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Disease Control Rate (DCR) was the number of participants who achieve a best overall response of CR, PR, or SD divided by the total number of participants randomized to the corresponding treatment arm as per RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

PK was determined by the minimum observed plasma concentration (Cmin). 1 Cycle (C) = 21 days (D).

PK was presented through graphical overlay comparison versus historic data. No numerical summary of data was intended or produced.

Number of participants with positive treatment emergent anti-ramucirumab antibodies (ADA) was summarized by treatment group.

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180.Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.

EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state.

EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. The second part is assessed using a VAS on which the patient rates their perceived health state, ranging from 0 millimeter (the worst health you can imagine) to 100 millimeter (the best health you can imagine).

All randomized participants who received at least 1 dose of study drug.

Participants received 8 mg/kg ramucirumab plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

All randomized participants

All randomized participants who received at least 1 dose of study drug

All randomized participants and all randomized participants who received at least 1 dose of study drug to align gender specific adverse event numbers.

Argentina

Hungary

Czechia

United Kingdom

Russia

Spain

Austria

South Korea

Sweden

Turkey

Belgium

Taiwan

Denmark

Mexico

Australia

France

Germany

Chief Medical Officer

Participants received placebo IV and placebo oral (indistinguishable and equivalent volume to ramucirumab and merestinib) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Pooled Placebo

All randomized participants. Censored participants: 8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine = 29; 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine = 34; Pooled Placebo = 25. Pooling is done in the placebo arm (Pooled Placebo) from both arms (Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine and Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine) for analysis purpose and combined as pre-specified in protocol.

Progression Free Survival (PFS)

Overall Survival (OS)

All randomized participants. Pooling is done in the placebo arm (Pooled Placebo) from both arms (Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine and Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine) for analysis purpose and combined as pre-specified in protocol.

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

Cycle 1 Day 8 (Week 1)

Cycle 2 Day 1 (Week 3)

Cycle 3 Day 1 (Week 6)

Cycle 4 Day 1 (Week 9)

Cycle 5 Day 1 (Week 12)

Cycle 7 Day 1 (Week 18)

Cycle 9 Day 1 (Week 24)

Cycle 13 Day 1 (Week 36)

All participants who received at least one dose of study drug and had evaluable PK data. As per protocol, Cmin of merestinib was not measured.

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Zero participants were analyzed as no data collected for summary analysis.

PK: Plasma Concentration of Merestinib

All randomized participants who received at least 1 dose of study drug with both baseline and at least one post baseline ADA assessments.

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

FACT-Hep

All randomized participants who received at least 1 dose of study drug with baseline and one post-baseline FACT-Hep Questionnaire.

Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep)

All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L data.

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score

Change From Baseline in Participant-Reported EQ-5D-5L Visual Analog Scale (VAS) Score

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Blood and Lymph Conditions

Breast Neoplasms

Bone Neoplasms

Bone Marrow Diseases

Breast Diseases

Skin Diseases

Neoplastic Processes

Bone Diseases

Hematologic Diseases

\*The merestinib does escalation timing will depend on the schedule of the other anticancer regimen\*

Subjects will receive merestinib 40mg PO Qday (dose level 1) for 2 to 4 weeks followed by 80mg PO daily (dose level 2) for 4 to 10 weeks

This is an open label, pharmacodynamics, intrapatient dose escalation phase 1B study.

a single arm, open label, pharmacodynamics, intrapatient dose escalation phase 1B study

Merestinib on Bone Metastases in Subjects With Breast Cancer

An Exploratory Phase 1B Study to Assess the Effects of Merestinib on Bone Metastases in Subjects With Breast Cancer

To assess the tolerability of merestinib in combination with standard breast cancer therapies.

To measure the change in urinary N-telopeptide level after 12 weeks of therapy with merestinib

To measure the absolute and percentage change in serum β-CTX, TRAP-5b, P1NP, and BSAP at time points from baseline to 12 weeks.

To evaluate determine time to skeletal-related event(s) following initiation of merestinib dosing

To evaluate change in pain as measured by pain scores during and after 12 weeks of merestinib treatment

To evaluate change in pain as measured by narcotic use) during and after 12 weeks of merestinib treatment

To evaluate the change in bone lesion uptake on NaF PET scan after 12 weeks of merestinib treatment

University of Utah

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Patients who fulfill eligibility criteria will be entered into the trial to receive Merestinib and LY2874455.

After the screening procedures confirm participation in the research study:

* The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have AML, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.
* Merestinib
* LY2874455

Oral, once a day, Merestinib Only- Lead in period on week. The followed by cycles on combination therapy with Merestinib and LY2874455 (28 days long)

This will be followed by cycles of combination therapy with merestinib and LY2874455. Each of these cycles are 28 days long. • LY2874455 will be taken by mouth twice a day. You may take LY2874455 twice daily for 14 days, 21 days, or 28 days each cycle depending on the dose level you are assigned.

LY2874455

Jacqueline S. Garcia, MD

This research study is studying a combination of two targeted therapies as a possible treatment for acute myeloid leukemia (AML) that has relapsed after initial treatment or did not fully respond.

The name of the study interventions involved in this study are:

* Merestinib
* LY2874455

* This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
* The FDA (the U.S. Food and Drug Administration) has not approved Merestinib or LY2874455 as a treatment for any disease.
* Merestinib is an oral drug known as a MET kinase inhibitor that is being developed as a treatment for patients with advanced cancer. MET inhibitors work by stopping a signal that a cell receives instructing it to grow.
* LY2874455 is an oral drug known as an FGFR inhibitor that is also being developed as a treatment for patients with advanced cancer. FGFR inhibitors work by stopping a signal that a cell receives instructing it to grow.
* In this research study, the investigators are investigating whether Merestinib and LY2874455 is safe to give in combination in patients with AML. In previous laboratory studies, it was found that leukemia cells responded to treatment with a MET inhibitor and an FGFR inhibitor. However, it is not yet known whether this will also be the case with LY2874455 and merestinib when given to participants.

open-label phase 1 study using a 3+3 design with planned dose escalation

Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 Study of Merestinib in Combination With LY2874455 in Relapsed or Refractory Acute Myeloid Leukemia

Dose-escalation will follow a standard 3+3 design exploring 3 dose levels of LY2874455 with a steady dose of Merestinib. We will escalate to next dose cohort if 0/3 or 1/6 participants have a DLT during the first cycle of therapy. If the rate of dose limiting toxicity (DLT) exceeds 30%, it is less likely that the dose of LY2874455 will be escalated.

Time to event summaries will use the Kaplan-Meier method.

Standard noncompartmental pharmacokinetic analysis will be employed including AUC 0-24 after initial and repeat administration.

Standard noncompartmental pharmacokinetic analysis will be employed including peak drug plasma concentration (Cmax) after initial and repeat administration.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer	NCT02711553	Biliary Tract C... Metastatic Canc... Advanced Cancer	Ramucirumab Merestinib Cisplatin Gemcitabine Placebo Oral Placebo IV	18 Years -	Eli Lilly and Company
Merestinib on Bone Metastases in Subjects With Breast Cancer	NCT03292536	Bone Metastases Breast Cancer	Merestinib	18 Years -	University of Utah
Merestinib on Bone Metastases in Subjects With Breast Cancer	NCT03292536	Bone Metastases Breast Cancer	Merestinib	18 Years -	University of Utah
Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia	NCT03125239	Relapsed Adult ... Refractory Adul...	Merestinib LY2874455	18 Years -	Dana-Farber Cancer Institute
A Study in Advanced Cancers Using Ramucirumab (LY3009806) and Other Targeted Agents	NCT02745769	Advanced Cancer Colorectal Canc... Mantle Cell Lym...	Ramucirumab Merestinib Abemaciclib	18 Years -	Eli Lilly and Company
A Study of Merestinib (LY2801653) in Japanese Participants With Advanced or Metastatic Cancer	NCT03027284	Advanced Cancer Metastatic Canc... Biliary Tract C... Cholangiocarcin... Gall Bladder Ca... Solid Tumor Non-Hodgkin's L...	Merestinib Cisplatin Gemcitabine	20 Years -	Eli Lilly and Company
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer	NCT02711553	Biliary Tract C... Metastatic Canc... Advanced Cancer	Ramucirumab Merestinib Cisplatin Gemcitabine Placebo Oral Placebo IV	18 Years -	Eli Lilly and Company
A Study in Advanced Cancers Using Ramucirumab (LY3009806) and Other Targeted Agents	NCT02745769	Advanced Cancer Colorectal Canc... Mantle Cell Lym...	Ramucirumab Merestinib Abemaciclib	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for merestinib

Every month we try and update this database with for merestinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for merestinib

Every month we try and update this database with for merestinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for merestinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.