MC# 19-01 - A Modular, Multi-Arm, Multi-Part, First Time in Patient Study to Evaluate the Safety and Tolerability of OMO-1, Alone and in Combination with Anti-Cancer Treatments, in Patients with Locally Advanced, Unresectable or Metastatic Solid Malignancies
Disease Type(s): Lung-NSCLC
Phase(s): I, II
Drug Classification(s): Targeted Therapy, Small Molecule
Molecular Target(s): MET
Mechanism of Action
OMO-1 is an inhibitor of the proto-oncogene and receptor tyrosine kinase (RTK) hepatocyte growth factor receptor (c-Met; HGFR; MET) and selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein.
In this study, the sponsor and investigators want to learn:
- How much of the study drug can be given with an acceptable level of side effects
- The effects of the study drug (good and bad) when given alone
- How much of the study drug is absorbed into the blood and how fast it is removed
- If research tests can be used in the future to predict who will benefit from the study drug
- Patients must be aged at least 18 years.
- Patients must have histological or cytological confirmation of locally advanced, unresectable or metastatic solid malignancy.
- Patients must have the following performance status: Eastern Co-operative Oncology Group (ECOG) ≤1 and life expectancy ≥3 months.
- Patients must have recovered from toxicities (except alopecia CTCAE Grade >2) of prior therapies (i.e. CTCAE Grade ≤2).
- Patients must have the ability to swallow and retain oral medication.
- Patients must have adequate organ functions as defined below:
- Females of child-bearing potential:
- Must use a highly effective method contraceptive measures during the study and for 6 months after the last dose of OMO-1. Contraceptives that are prone to drug-drug interactions may not be effective due to a potential CYP3A4 interaction with OMO-1.
- Must not be breast feeding.
- Must have a negative pregnancy test prior to start of dosing with OMO-1.
- Sexually active male patients must be willing to use barrier contraception (i.e., condoms with spermicide) with all sexual partners for the duration of the study and for 6 months after the last OMO-1 administration.
- Females of child-bearing potential:
- Patients recruited into Module 1, Part B cohorts:
- Tumours that are MET gene amplified and/or mutated. At least one lesion, not previously irradiated, that can be accurately measured at baseline.
- No prior therapy with a selective MET inhibitor. No history of other malignancy (except non-melanoma skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years prior to the first dose of OMO-1.
- No metastasis limited to the bone only.
- Patients receiving other cancer therapy, or other investigational product, apart from the combination agent(s) described in the relevant combination module(s).
- Patients who have received radiotherapy for the primary tumor within 1 week from screening visit.
- Patients receiving metformin
- Patients receiving medications that are known to have potent AO inhibitory activity (e.g. Raloxifene)
- Patients with prior splenectomy.
- Patients testing positive for human immunodeficiency virus (HIV) infection, hepatitis B based on findings of persistent hepatitis B virus surface antigen (HBsAg) or other serology test, hepatitis C virus (HCV) or Epstein-Barr Virus (EBV) infection.
- Patients with current, or a history of, uveitis.
- Patients with any known uncontrolled inter-current illness including ongoing or active infections, symptomatic congestive heart failure, conditions that could adversely be affected by hypertension or tachycardia, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with a history or clinical evidence of neoplastic central nervous system (CNS) involvement if not stable for 9 weeks prior to the first dose of study treatment.
- Patients with major and/or planned surgery within 12 weeks of the first dose of study treatment.
- Patients with pleural effusions and/or ascites, due to malignancy, requiring paracentesis every 2 weeks or more frequently.
- Patients with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in OMO-1.
- Patients with abnormal urinary function and outflow obstruction.
- Dallas, TX - Mary Crowley Cancer Research - Medical City