RECRUITINGPhase 1INTERVENTIONAL
Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours
A Phase 1 Study to Determine the Safety, and Pharmacokinetics of the Selective MET Kinase Inhibitor, DO-2 in Patients With Advanced or Refractory Solid Tumours
About This Trial
This study is a first-in-human, open-label, 2-part, Phase 1 dose escalation study of DO-2, administered orally to patients with advanced or refractory solid tumours, with MET aberrations, and no available, approved therapeutic alternative. The dose escalation is completed, Part 2 of the study is ongoing.
Who May Be Eligible (Plain English)
Who May Qualify:
- 18 years or older
- diagnosed by tissue sample (biopsy-confirmed) locally advanced, unresectable or metastatic NSCLC, no longer eligible for approved, available standard therapies. To be entered patients must have proven MET exon 14 skipping mutation, determined by local next generation sequencing (NGS), whole exome sequencing (WES), whole transcriptome sequencing (WTS) or other genomic analysis methods, from an assessment not older than 3 months
- measurable disease in accordance with RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- adequate bone marrow function, without the support of cytokines
- adequate liver function
- adequate renal function with serum creatinine \<1 x institutional UNL and GFR within normal range
- agree to follow the contraception requirements of the trial
- signed willing to sign a consent form, indicating study patients understand the purpose of and procedures required for the study and are willing to participate in the study.
Who Should NOT Join This Trial:
- tumour harbouring other known oncogenic mutations promoting tumour growth
- major surgery within 3 weeks before enrolment
- chemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy, or any other study drug within 3 weeks before study drug administration
- antibody based cancer therapy within 4 weeks before administration of the first dose of DO-2
- patients who became progressive on previous treatment with a MET-kinase inhibitor
- patients with brain metastases are excluded unless all of the following criteria are met:
1. CNS lesions are asymptomatic and previously treated
2. No ongoing requirement for corticosteroids as therapy for cancer that has spread to the brain
3. Imaging demonstrates stability of disease \> 28 days from last treatment for cancer that has spread to the brain
- leptomeningeal involvement (leptomeningeal carcinomatosis)
...See full criteria on ClinicalTrials.gov
Always talk to your doctor about whether this trial is right for you.
Original Eligibility Criteria
View original clinical language
Inclusion Criteria:
* 18 years or older
* histologically or cytologically confirmed locally advanced, unresectable or metastatic NSCLC, no longer eligible for approved, available standard therapies. To be entered patients must have proven MET exon 14 skipping mutation, determined by local next generation sequencing (NGS), whole exome sequencing (WES), whole transcriptome sequencing (WTS) or other genomic analysis methods, from an assessment not older than 3 months
* measurable disease in accordance with RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* adequate bone marrow function, without the support of cytokines
* adequate liver function
* adequate renal function with serum creatinine \<1 x institutional UNL and GFR within normal range
* agree to follow the contraception requirements of the trial
* signed informed consent, indicating study patients understand the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion Criteria:
* tumour harbouring other known oncogenic mutations promoting tumour growth
* major surgery within 3 weeks before enrolment
* chemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy, or any other study drug within 3 weeks before study drug administration
* antibody based cancer therapy within 4 weeks before administration of the first dose of DO-2
* patients who became progressive on previous treatment with a MET-kinase inhibitor
* patients with brain metastases are excluded unless all of the following criteria are met:
1. CNS lesions are asymptomatic and previously treated
2. No ongoing requirement for corticosteroids as therapy for CNS metastases
3. Imaging demonstrates stability of disease \> 28 days from last treatment for CNS metastases
* leptomeningeal involvement (leptomeningeal carcinomatosis)
* history of uncontrolled heart disease including unstable angina, congestive heart failure, myocardial infarction within preceding 12 months, clinically significant rhythm or conduction abnormality, congenital long QT syndrome, obligate use of a cardiac pacemaker, QTc at screening greater than 450 milliseconds in males and greater than 470 milliseconds in females
* uncontrolled arterial hypertension despite appropriate therapy
* positive pregnancy test (urinary beta-hCG) at screening (applicable to women of child-bearing potential who are sexually active)
* mental status alteration or history of major psychiatric illness, which may potentially impair patient's compliance with study procedures
* signs and symptoms of active infection requiring systemic therapy
* other medical condition (e.g. pre-existing kidney dysfunction) that in the opinion of the investigator makes it undesirable for a patient to participate
* inability or unwillingness to swallow capsules and malabsorption syndrome or other condition that would interfere with enteral absorption
Treatments Being Tested
DRUG
DO-2
Deuterated MET kinase inhibitor
Locations (13)
Institut Roi Albert II - UC Louvain
Brussels, Belgium
UZA
Edegem, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
Institut Bergonie
Bordeaux, France
Institut Cœur Poumon - CHU Lille
Lille, France
Centre Léon Bérard
Lyon, France
Hôpitaux Universitaires de Marseille Timone
Marseille, France
Centre Antoine Lacassagne
Nice, France
Centre Hospitalier Universitaire De Rennes
Rennes, France
Institut Gustave Roussy
Villejuif, France
Radboud UMC
Nijmegen, Netherlands
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Rotterdam, Netherlands