OMO-1 in Solid Malignancies

NCT03138083 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: OMO1.01.02
• Study Type: interventional
• Target: 40
• Locations: 5 countries
• Sites: 11

Brief 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.

Conditions

Neoplasms

Keywords

Mesenchymal-epithelial transition factor (MET) inhibitor

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events including dose-limiting toxicities

  The proportion of patients with treatment-emergent (serious) adverse events including dose-limiting toxicity (DLT)

  Baseline (C1D1) until 28 days after last administration of OMO-1

• Incidence of clinically significant abnormal measurements in physical examination, ophthalmological examination, vital signs, electrocardiogram (ECG), pregnancy test, lab tests and ECOG performance status

  Physical examination and ophthalmological examination, vital signs; electrocardiogram (ECG); pregnancy test; haematology; clinical chemistry; urinalysis; plasma/renal makers; tumour markers; ECOG performance status

  Screening until 28 days after last administration of OMO-1

Secondary Outcomes (5)

• Objective Response Rate

  Screening until 28 days after last administration of OMO-1

• Percentage change in tumour size

  Screening until 28 days after last administration of OMO-1

• Maximal OMO-1 plasma concentration Cmax

  Baseline (C1D1) and D1 in even cycles (C) until end of treatment (Part A) ; Baseline and C2D1 (Part B)

• Area under the OMO-1 plasma concentration curve (AUC)

  Baseline (C1D1) and D1 in even cycles (C) until end of treatment (Part A) ; Baseline and C2D1 (Part B)

• 'Proof of mechanism' and 'proof of principle' pharmacodynamic biomarkers, including markers of tumour cell proliferation and apoptosis.

  Screening until end of treatment

Study Arms (6)

Module 1 Monotherapy Multiple Ascending Dose

EXPERIMENTAL

Multiple ascending dose cohorts dosing OMO-1 (bid) monotherapy in all comer patients up to a maximally tolerated or maximally feasible dose

Drug: OMO-1

Module 1 Monotherapy Paired Biopsy

EXPERIMENTAL

Paired biopsy cohort(s) dosing OMO-1 (bid) monotherapy in patients selected for MET dependent tumours at minimally biologically active doses and above

Drug: OMO-1

Module 1 Monotherapy Expansion Cohort(s)

EXPERIMENTAL

Expansion cohort(s) dosing OMO-1 (bid) monotherapy in patients selected for MET dependent tumours at recommended phase 2 dose (RP2D)

Drug: OMO-1

Module 2 Combination with EGFR-TKI Multiple Ascending Dose

EXPERIMENTAL

Multiple 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

Drug: OMO-1

Module 2 Combination with EGFR-TKI Paired Biopsy

EXPERIMENTAL

Paired biopsy cohort(s) dosing OMO-1 (bid) in combination with EGFR-TKI in MET amplified patients at minimally biologically active doses and above

Drug: OMO-1

Module 2 Combination with EGFR-TKI Expansion Cohort

EXPERIMENTAL

Expansion cohort dosing OMO-1 (bid) monotherapy in combination with EGFR-TKI in MET amplified patients at recommended phase 2 (combination) dose (RP2D)

Drug: OMO-1

Interventions

OMO-1 DRUG

OMO-1 is a small molecule inhibitor of the enzymatic activity of the MET receptor tyrosine kinase

Also known as: JNJ-38877618

Module 1 Monotherapy Expansion Cohort(s); Module 1 Monotherapy Multiple Ascending Dose; Module 1 Monotherapy Paired Biopsy; Module 2 Combination with EGFR-TKI Expansion Cohort; Module 2 Combination with EGFR-TKI Multiple Ascending Dose; Module 2 Combination with EGFR-TKI Paired Biopsy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Octimet Oncology N.V.: lead

Study Sites (11)

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

University Hospital Antwerp

Edegem, Belgium

Location

Institut Bergonie

Bordeaux, France

Location

Hôpital La Timone

Marseille, France

Location

lnstitut Gustave Roussy

Villejuif, France

Location

Erasmus MC

Rotterdam, Netherlands

Location

UMCU Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

University of Oxford, Department of Oncology

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Martijn Lolkema, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A modular, multi-arm, multi-part, first time in patient study

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 3, 2017
• Study Start: August 8, 2017
• Primary Completion: May 25, 2020
• Study Completion: May 25, 2020
• Last Updated: June 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (2); US (1); FR (3); GB (4)