OMO-1 in Solid Malignancies

• Status: Terminated
• Trial end date: 2020-05-25
• Target enrollment: 0
• Participant gender: All

Summary

This is a modular, first time in patient, open-label, multicentre study of OMO-1, administered orally, alone and in combination with anti-cancer treatments, in patients with locally advanced, unresectable or metastatic solid malignancies.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Octimet Oncology N.V.

Criteria

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.