Phase 1 Study of IM156 in Patients With Advanced Solid Tumor and Lymphoma

Study Overview
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Brief Summary
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The main purpose of first-in-human IM156 study is to evaluate the safety and tolerability, and to determine the maximum tolerated dose and recommended phase 2 dose of IM156.

Official Title
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A Multi Center, Open-label, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Preliminary Efficacy of IM156 in Patients With Advanced Solid Tumors and Lymphoma

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: IM156


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 19 years old. Patients histologically or cytologically diagnosed with advanced solid tumor. Patients for whom no standard therapies are available or who have failed in the existing conventional therapies. Patients with a measurable or evaluable lesion by the RECIST v1.1 [for patients with recurrent glioblastoma, the RANO guideline is applied]. Patients with the Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. Patients with the adequate function of bone marrow, kidney and liver as follows. ① Absolute Neutrophil Count ≥ 1,500/mm³, Platelet ≥ 100,000/mm³, Hemoglobin ≥ 9.0 g/dL (In case of hemoglobin < 9.0 g/dL, the patient can be enrolled if the value is reversed to ≥ 9.0 g/dL. However, blood transfusion to meet this criterion within 1 week is not allowed.) ② Serum creatinine ≤ 1.5 X upper limit of normal (ULN) ③ Total bilirubin ≤ 1.5 X UNL, AST, ALT ≤ 3 ×ULN (for patients with liver disease ≤ 5 ×ULN) ④ Fasting serum glucose ≤ 160 mg/dL Patients with the life expectancy ≥ 12 weeks. Patients who have agreed to use acceptable methods for contraception during the study treatment period. (e.g.: sterilization of the patient and his/her partner, intrauterine device of the partner, barrier contraception, combination with diaphragm or condom) Patients who have voluntarily signed an informed consent to participate in this clinical study. Exclusion Criteria: Patients with a history of hypersensitivity to the active ingredient or any component of the investigational product or biguanides. Patients with a current evidence of diabetes mellitus who are currently being treated with another biguanide (e.g., metformin) Patients with a history of serious gastrointestinal bleeding within 6 weeks prior to screening or patients with any disease possibly affecting the absorption of oral agents. (malabsorption syndrome, hemorrhagic gastric ulcer, etc.) At the time of screening, For patients who underwent major surgery, at least 4 weeks have not elapsed after surgery. For patients who underwent radiotherapy, at least 3 weeks have not elapsed from the last treatment day. For patients who underwent chemotherapy, at least 3 weeks have not elapsed from the last treatment day. (6 weeks for nitrosurea compounds). For patients treated with biologic agents including hormone therapy, at least 5 half-lives or 3 weeks, whichever is shorter. Patients who have not been recovered from the toxicities to grade 1 of the therapy received prior to screening. Pregnant women or nursing mothers. Patients who were administered another investigational product within 3 weeks prior to screening. Patients with uncontrolled metastasis to the central nervous system. However, patients with treated and stable brain metastases (stable at least for 30 days on radiology imaging) are allowed to enroll. Patients with suspected serious infectious diseases, intestinal paralysis, bowel obstruction, interstitial pneumonia, or pulmonary fibrosis. Patients with a history of psychiatric disorders likely to threaten the compliance with this protocol. Patients with a history of alcohol or drug abuse within 12 weeks prior to screening. Human Immunodeficiency Virus (HIV) infection or active hepatitis B or C. Patients with no detectable viral load could be enrolled. Patients with severe traumatism. Patients with any clinically significant abnormal intestinal findings that may interfere with the administration, passage, or absorption of the investigational product, which makes the patients unable to orally take the tablet form of drugs. Patients with severe cardiac disorders (e.g. myocardial infarction, congestive heart failure, arrhythmia showing dramatic change in electrocardiogram (ECG), severe or unstable angina, other serious cardiac disorders) or patients with comorbidities of other serious internal disorders (e.g. uncontrolled diabetes mellitus, chronic obstructive pulmonary disorder, renal failure, etc.) on investigator's judgment. Patients who are otherwise considered to be ineligible for this study on investigator's judgment.

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IM156, Dose escalation<br> | Drug: IM156<br>* Sequential 3+3 design.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | Evaluate the safety and tolerability to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) |  | 4 weeks | 
| Time to Cmax (Tmax) |  | 4 weeks | 
| Area under the curve (AUC) |  | 4 weeks | 
| Plasma half life (T1/2) |  | 4 weeks | 
| Volume of distribution (V/F) |  | 4 weeks | 
| Plasma Clearance (CL/F) |  | 4 weeks | 
| Exploratory Surrogate Biomarker | Explore potential surrogate biomarkers in peripheral blood mononuclear cells (PBMC). | 2 weeks | 
| Preliminary tumor response | Assess objective tumor response and progression based on the Response Evaluation Criteria for Solid Tumor (RECIST) v1.1 [for patients with recurrent glioblastoma, the Response Assessment in Neuro-Oncology (RANO) guideline is applied]. | Every 8 weeks up to end of treatment (EOT) |