Locally advanced, unresectable or metastatic solid malignancies MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: OMO-1
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: -
Other descriptive name: OMO-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pr
Sponsors
OCTIMET Oncology NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core: • 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. • Patients must have recovered from toxicities of prior therapies (i.e. CTCAE Grade =1). • Ability to swallow and retain oral medication. • Adequate organ functions. • Not receiving other cancer therapy, or other investigational product, apart from the combination agent(s) described in the relevant combination module(s). • No radiotherapy for the primary tumour within 1 week from screening visit. • Not receiving medications predominantly metabolized by CYP2B6. Washout period for medications predominantly metabolized by CYP2B6, apart for tamoxifen, is 7 days prior to the first dose of study treatment. Washout period for tamoxifen is 2 months prior to the first dose of study treatment • Not receiving cannabinoid substances and St. John’s Wort. Washout period for cannabinoid substances and St. John’s Wort is 5 and 7 days respectively prior to the first dose of study treatment. • Not receiving medication that are known to have potent aldehyde oxidase (AO) inhibitory activity. Washout period for medications that are known to have potent AO inhibitory activity is 7 days prior to the first dose of study treatment. • No prior splenectomy. • No current or history of uveitis. • No 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. • No 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. Note: Patients with glioblastomas are allowed if their symptoms are stable. • No current or 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 sequential biopsy cohorts of Part A: • At least 1 lesion suitable for biopsy. • Tumours that are MET gene amplified and/or mutated. (MET gene amplified and/or mutated status defined in the laboratory manual). • No prior therapy with a selective MET inhibitor. Patients recruited into Part B cohorts: • Tumours that are MET gene amplified and/or mutated. (MET gene amplified and/or mutated status defined in the laboratory manual). • At least one lesion, not previously irradiated, that can be accurately measured at baseline. • No prior therapy with a selective MET inhibitor. • No co-incident malignancy that would impact on survival. • No metastasis limited to the bone only. Module 2: Patient recruited into both Part A and Part B: • Tumours that are EGFR gene mutant that are currently progressing on treatment with a small molecule EGFR-TKI (gefitinib, erlotinib, afatinib or osimertinib administered as per the relevant medication package insert, or recognised dose reduction in the case of afatinib). Enrolment must be restricted to patients that are resistant to all relevant EGFR TKI therapy according to their tumour muta
Exclusion criteria
Exclusion criteria: 1. Patients receiving other cancer therapy, or other investigational product, apart from the combination agent(s) described in the relevant combination module(s). Note: Bisphosphonates and granulocyte-colony stimulating factor (GCSF) are acceptable. Immunotherapy’s such as mAbs, interferons and cytokines should not be taken other than the combination therapy agent. Immunosuppressant’s such as cyclosporine, rapamycin, tacrolimus, rituximab, alemtuzumab, natalizumab etc, should not be taken other than the combination therapy agent. Hormone replacement therapy (HRT) and stable treatment of >6 months with luteinizing hormone releasing hormone (LHRH) analogues are acceptable. During the study period, patients using HRT and bisphosphonates should maintain a constant dose and should not change existing regimen. However, if a change in HRT is indicated, e.g. due to intolerable adverse effects, the regimen may be modified but change should be minimized thereafter. Washout period for cytotoxic drugs and other mAbs is 21 days prior to the first dose of study treatment. Washout period for approved molecular targeted non-cytotoxic drugs is 5 half-lives prior to the first dose of study treatment. 2. Patients who have received radiotherapy for the primary tumour within 1 week from screening visit. 3. Patients receiving medications predominantly metabolized by CYP2B6 (refer to Section 12.1 for more information). Washout period for medications predominantly metabolized by CYP2B6, apart for tamoxifen, is 7 days prior to the first dose of study treatment. Washout period for tamoxifen is 2 months prior to the first dose of study treatment. 4. Patients receiving cannabinoid substances. Washout period for cannabinoid substances is 5 days prior to the first dose of study treatment. 5. Patients receiving St. John’s Wort. Washout period for St. John’s Wort is 7 days prior to the first dose of study treatment. 6. Patients receiving medications that are known to have potent AO inhibitory activity (refer to Section 12.1 for more information). Washout period for medications that are known to have potent AO inhibitory activity is 7 days prior to the first dose of study treatment. 7. Patients with prior splenectomy. 8. 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. 9. Patients with current, or a history of, uveitis. 10. 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. 11. 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. Note: Patients with glioblastomas are allowed if their symptoms are stable. 12. Patients with major and/or planned surgery within 12 weeks of the first dose of study treatment. 13. Patients with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in OMO 1. 14. Patients with nephrolithiasis; 15. Patients with current, or a history of any seizure or seizure disorder. This includes receiving, or having re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of OMO-1 when given orally to patients with locally advanced, unresectable or metastatic solid malignancies, alone or in combination with anti-cancer treatments, and define the doses and schedules for further clinical evaluation;Secondary Objective: • To characterise the PK and pharmacodynamics (PDc) of OMO 1, following a single dose and/or at steady state after multiple dosing, when given orally alone or in combination with anti-cancer treatments. • To assess the preliminary efficacy of OMO-1 by Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. locally. ;Primary end point(s): Module 1: Safety Endpoints The following safety parameters will be assessed: •Physical examination and ophthalmological examination, vital signs, and ECOG performance status •12-lead ECG •Laboratory parameters: Haematology, coagulation, clinical chemistry, serum renal markers, urinalysis, urine renal markers, and tumour markers (patients with relevant tumour types) •Number of DLTs •Adverse events (AEs) (graded by CTCAE) (including pregnancy) •Number of withdrawals, discontinuations and dose reductions Module 2 Safety Endpoints The following safety parameters will be assessed: • Physical examination and ophthalmological examination, vital signs, and ECOG performance status • 12-lead ECG • Laboratory parameters: Haematology, coagulation, clinical chemistry, serum renal markers, urinalysis, urine renal markers, and tumour markers (patients with relevant tumour types) • Number of DLTs • AEs (graded by CTCAE) (including pregnancy) • Number of withdrawals, discontinuations and dose reductions ;Timepoint(s) of evaluation of this end point: The investigator will assess the safety end points at each visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Module 1: Efficacy Endpoints Key efficacy endpoints for Part A and Part B: •Tumour response defined as: oPartial CR using standard RECIST 1.1 criteria, providing ORR and DRR (refer to Section 22.8) •Time to progression (TTP) Pharmacokinetic Endpoints •MBAD (as defined in Section 22.4.6.3.3) •Dose linearity of PK parameters for doses up to and beyond MBAD Pharmacodynamic Endpoints •Tumour tissue PoM oPaired tumour biopsies: Reduction in % and intensity of phospho MET positive tumour cells (immunohistochemistry [IHC]) •Surrogate tissue PoP oSerum: ?Increase in serum creatinine (OCT 2 inhibition) oPlasma: Reduction in kynurenine/tryptophan ratio Increased ratios between effector (CD8+) T cells and Tregs and between effector (CD8+) T cells CD4+ T cells ?Decreased neutrophil- to- lymphocyte ratio (NLR) and other markers of inflammation (platelet-to-lymphocyte ratio [PLR]/systemic immune inflammation [SIII]) ?Modulation of ShedMET levels ?Modulation of HGF levels •Tumour tissue PoP oPaired tumour biopsies (n=6 evaluable biopsy pairs): Reduction in phenotypic biomarker (e.g. Ki67) in tumour cells Increase in apoptosis biomarker (e.g. cleaved caspase) in tumour cells Reduction in pERK in tumour cells Reduction in pAKT in tumour cells Reduction in pGAB2 in tumour cells Reduction in TILs Significant modulation of immune oncology biomarker panel (e.g. Nanostring immune-oncology profile) Reduction of MET amp/mut cftDNA in patient positive for this at baseline Module 2 Efficacy Endpoints Key efficacy endpoints: • Tumour response defined as: o Partial or CR (RECIST 1.1), providing ORR and DRR (refer to Section 23.8) • TTP Pharmacokinetic Endpoints • Dose linearity of PK parameters for doses for all doses of OMO 1 • Trough levels of the EGFR TKIs Pharmacodynamic Endpoints • Tumour tissue PoM o Paired tumour biopsies: ? Reduction in % and intensity of phospho MET positive tumour cells (IHC) • Surrogate tissue PoP o Plasma: ? Decreased NLR • Tumour ti | — |
Countries
Belgium, France, Netherlands, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Desk
OCTIMET Oncology NV
Outcome results
None listed