OMO-1 in Solid Malignancies

Inclusion Criteria:

• Aged at least 18 years
• Provision of signed and dated, written informed consent.
• Histological or cytological confirmation of locally advanced, unresectable or metastatic solid malignancy.
• Performance status: Eastern Co-operative Oncology Group (ECOG) ≤1 and life expectancy ≥3 months.
• Ability to swallow and retain oral medication.
• Adequate organ functions.

• Females of child-bearing potential:

  • Must use a highly effective method contraceptive measures during the study and for 1 month after the last dose of OMO 1.
  • Must not be breast feeding.
  • Must have a negative pregnancy test prior to start of dosing.
• Sexually active male patients must be willing to use barrier contraception

Exclusion Criteria:

• Patients receiving other cancer therapy, or other investigational product apart from the combination agent(s) described in the relevant combination modules.
• Patients who have received radiotherapy for the primary tumour within 1 week from the screening visit.
• Patients receiving medications predominantly metabolized by CYP2B6.
• Patients receiving cannabinoid substances.
• Patients receiving St John's Wort.
• Patients receiving medications that are known to have potent aldehyde oxidase (AO) inhibitory activity.
• 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 any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in OMO-1.
• Patients with nephrolithiasis.
• Patients with current, or a history of any seizure or seizure disorder. This includes receiving, or having received, seizure threshold-raising medication for the treatment of epilepsy.

In addition to the main core eligibility criteria, Module specific eligibility criteria include:

Module 1:

Patient recruited into the paired biopsy cohorts of Part A must have:

• at least 1 lesion suitable for biopsy.
• tumours that are MET gene amplified and/or mutated.
• had no prior therapy with a selective MET inhibitor.

Patients recruited into Part B cohorts must have:

• tumours that are MET gene amplified and/or mutated.
• at least one lesion, not previously irradiated, that can be accurately measured at baseline.
• had no prior therapy with a selective MET inhibitor.
• no coinciding malignancy that would impact on survival.
• no metastasis limited to the bone only.

Module 2:

Patients recruited into Part A and Part B cohorts must have:

• tumours that are EGFR gene mutant that are currently progressing on treatment with a small molecule EGFR-TKI. Enrolment must be restricted to patients that are resistant to all relevant EGFR TKI therapy according to their tumour mutated status.
• received the EGFR-TKI as monotherapy for at least 12 weeks.
• tolerated their current dose of EGFR-TKI for at least 12 weeks.
• tumours that are MET gene amplified.
• had no prior therapy with a selective MET inhibitor.
• had no prior EGFR-TKI treatment of >2 lines.
• no past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• no significant GI disorders with diarrhoea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >1 diarrhoea of any aetiology at the enrolment.
• no contra-indications (as per the relevant medication package insert) for therapy with the EGFR-TKI routinely used by their oncology unit.

In addition, patients recruited into Module 2 Part B cohorts must have:

• at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with CT or MRI and which is suitable for accurate repeated assessment.
• no coinciding malignancy that would impact on survival.
• no metastasis limited to the bone only.