Clinical Trials /

OMO-1 in Solid Malignancies

NCT03138083

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: OMO-1 in Solid Malignancies
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: OMO1.01.02
  • NCT ID: NCT03138083

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
OMO-1JNJ-38877618Module 1 Monotherapy Expansion Cohort(s)

Purpose

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.

Detailed Description

      The study will consist of a number of study modules. The initial Module 1 will evaluate OMO-1
      as monotherapy to provide dose(s) and schedule(s) for further Modules of combination therapy.

      Module 2 will evaluate OMO-1 in combination with small molecule EGFR-TKIs.

      Study modules will consist of a Part A (dose finding) and an optional Part B (cohort
      expansion). The option to start Part B and add further modules will be the decision of the
      safety review committee, based on emerging preclinical anti-tumour data and, safety and
      tolerability information from the study as a whole.

      For all modules, Part A cohorts may be expanded by up to 12 additional patients at doses (at
      or above the MBAD) that have been confirmed to be tolerated. These patients will have
      mandatory paired biopsies to assess the tumour for relevant PDc biomarkers, and to explore
      further the tolerability, safety and PK activity at these doses.

      In all combination modules, the dose of each combination agent investigated will not exceed
      their current recommended dose. The starting dose of OMO-1 in combination modules will not
      exceed the one currently tolerated in Module 1 (monotherapy). For cohorts in which OMO-1 is
      dosed in combination with cytotoxic chemotherapy, dosing will not continue once the cycles of
      chemotherapy have been completed.
    

Trial Arms

NameTypeDescriptionInterventions
Module 1 Monotherapy Multiple Ascending DoseExperimentalMultiple ascending dose cohorts dosing OMO-1 (bid) monotherapy in all comer patients up to a maximally tolerated or maximally feasible dose
  • OMO-1
Module 1 Monotherapy Paired BiopsyExperimentalPaired biopsy cohort(s) dosing OMO-1 (bid) monotherapy in patients selected for MET dependent tumours at minimally biologically active doses and above
  • OMO-1
Module 1 Monotherapy Expansion Cohort(s)ExperimentalExpansion cohort(s) dosing OMO-1 (bid) monotherapy in patients selected for MET dependent tumours at recommended phase 2 dose (RP2D)
  • OMO-1
Module 2 Combination with EGFR-TKI Multiple Ascending DoseExperimentalMultiple ascending dose cohorts dosing OMO-1 (bid) in combination with EGFR-TKI in MET amplified patients up to a maximally tolerated or maximally feasible dose
  • OMO-1
Module 2 Combination with EGFR-TKI Paired BiopsyExperimentalPaired biopsy cohort(s) dosing OMO-1 (bid) in combination with EGFR-TKI in MET amplified patients at minimally biologically active doses and above
  • OMO-1
Module 2 Combination with EGFR-TKI Expansion CohortExperimentalExpansion cohort dosing OMO-1 (bid) monotherapy in combination with EGFR-TKI in MET amplified patients at recommended phase 2 (combination) dose (RP2D)
  • OMO-1

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events including dose-limiting toxicities
Time Frame:Baseline (C1D1) until 28 days after last administration of OMO-1
Safety Issue:
Description:The proportion of patients with treatment-emergent (serious) adverse events including dose-limiting toxicity (DLT)

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:Screening until 28 days after last administration of OMO-1
Safety Issue:
Description:Objective response rate (ORR) by RECIST 1.1 - the proportion of patients with a confirmed reduction in tumour burden of a predefined amount (this will include short lived responses).
Measure:Percentage change in tumour size
Time Frame:Screening until 28 days after last administration of OMO-1
Safety Issue:
Description:Percentage change in tumour size will be determined for patients with measurable disease at baseline and is derived at each visit by the percentage change from baseline in the sum of the diameters of target lesions. The best percentage change in tumour size will be the patient's value representing the largest decrease (or smallest increase) from baseline in tumour size.
Measure:Maximal OMO-1 plasma concentration Cmax
Time Frame:Baseline (C1D1) and D1 in even cycles (C) until end of treatment (Part A) ; Baseline and C2D1 (Part B)
Safety Issue:
Description:Measurement of OMO-1 levels in plasma over time to calculate Cmax
Measure:Area under the OMO-1 plasma concentration curve (AUC)
Time Frame:Baseline (C1D1) and D1 in even cycles (C) until end of treatment (Part A) ; Baseline and C2D1 (Part B)
Safety Issue:
Description:Measurement of OMO-1 levels in plasma over time to calculate AUC
Measure:'Proof of mechanism' and 'proof of principle' pharmacodynamic biomarkers, including markers of tumour cell proliferation and apoptosis.
Time Frame:Screening until end of treatment
Safety Issue:
Description:Measurement of levels of 'Proof of mechanism' and 'proof of principle' pharmacodynamic biomarkers, including markers of tumour cell proliferation and apoptosis.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Octimet Oncology N.V.

Trial Keywords

  • Mesenchymal-epithelial transition factor (MET) inhibitor

Last Updated

September 19, 2019