A Study of Merestinib (LY2801653) in Japanese Participants With Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate tolerability of merestinib monotherapy or in combination with other anti-cancer agents in Japanese participants with advanced and/or metastatic cancer.

Official Title
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A Phase I Study of Merestinib Monotherapy or in Combination With Other Anti-Cancer Agents in Japanese Patients With Advanced and/or Metastatic Cancer

Conditions
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Advanced Cancer, Metastatic Cancer, Biliary Tract Carcinoma, Cholangiocarcinoma, Gall Bladder Carcinoma, Solid Tumor, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Merestinib
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: Histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic (solid tumors or non-Hodgkin's lymphoma). Part B: Biliary tract carcinoma that is unresectable, recurrent, or metastatic. The participant must not have received prior systemic front-line therapy for metastatic or resectable disease. Part A: Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Cheson Criteria. Part B: Measurable disease as defined by RECIST v1.1. Adequate organ function including hematologic, hepatic and renal. Eastern Cooperative Oncology Group (ECOG) scale of 0 or 1. Are able to swallow tablets. For participants in Part B, a tumor tissue sample is mandatory for biomarker analysis. Males must agree to use medically approved barrier contraceptive precautions during the study and for 3 months following the last dose of study drug. Females with childbearing potential: Must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug, must have had a negative serum or urine pregnancy test ≤7 days before the first dose of study drug. A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding enters the study, breastfeeding must cease from the day of the first study drug administration until at least 3 months after the last administration. Exclusion Criteria: Have serious pre-existing medical conditions. Have a chronic underlying infection. Have symptomatic central nervous system malignancy or metastasis. Have an active fungal, bacterial, and/or known viral infection. Part B: Have mixed hepatocellular biliary tract carcinoma histology. Have liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant. Have a history of congestive heart failure with New York Heart Association (NYHA) class greater than 2, unstable angina, or have recent history of myocardial infarction, transient ischemic attacks, stroke, or arterial or venous vascular disease. Have a corrected QT interval >470 milliseconds as calculated be the Fredericia equation. Have a second primary malignancy that, in the judgment of the investigator, and sponsor may affect the interpretation of results. Have any evidence of clinically active interstitial lung disease (ILD).

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Merestinib (Part A Dose Level 1)<br>Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met. | Drug: Merestinib<br>* Administered orally<br>* Other names: LY2801653;|
| Experimental: Merestinib (Part A Dose Level 2)<br>Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met. | Drug: Merestinib<br>* Administered orally<br>* Other names: LY2801653;|
| Experimental: Merestinib + Cisplatin + Gemcitabine (Part B)<br>Merestinib administered orally with cisplatin and gemcitabine administered intravenously (IV). Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met, but Cisplatin and gemcitabine treatment will be limited to a maximum of 8 cycles. | Drug: Merestinib<br>* Administered orally<br>* Other names: LY2801653;Drug: Cisplatin<br>* Administered IV<br>Drug: Gemcitabine<br>* Administered IV<br>* Other names: LY188011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Merestinib Dose-Limiting Toxicities (DLTs) | Number of participants with DLTs | Cycle 1 (Part A = 28 Days or Part B = 21 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Merestinib and its Metabolites | PK: Cmax of merestinib and its metabolites | Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles) | 
| PK: Area Under the Concentration Time Curve (AUC) of Merestinib and its Metabolites | PK: AUC of merestinib and its metabolites | Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles) | 
| Objective Response Rate (ORR): Percentage of Participants With a Complete or Partial Response | ORR: Percentage of participants with a complete or partial response | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months) | 
| Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of Complete Response, Partial Response, and Stable Disease | DCR: Percentage of participants with a best overall response of complete response, partial response, and stable disease | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasm