Adult Solid Tumor, Advanced Solid Tumor, Hereditary Renal Papillary Cancer, Lung Cancer, Non-small Cell Carcinoma, Non-small Cell Lung Cancer, Refractory Tumor
Conditions
Brief summary
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.
Detailed description
In Part 1, a Simon Design 3 accelerated titration design will be followed. One patient will be enrolled per cohort, until grade 2 toxicity is observed. Three sequential patients per cohort will be enrolled thereafter, with a minimum of 1 week between first dose administration in the first patient and the subsequent ones, in those latter cohorts. In part 2, up to 30 evaluable patients with locally advanced, unresectable or metastatic non-small-cell cancer (NSCLC), no longer eligible for approved, available standard therapies and having tumour harbouring MET exon14 skipping mutation from an assessment not older than 3 months, will received DO-2 at the selected dose.
Interventions
DRUGDO-2
Deuterated MET kinase inhibitor
Sponsors
DeuterOncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation followed by a study single expansion arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects who experience specific treatment-related adverse events (TRAEs) | Baseline through study completion, an average of 12 months | Number of subjects with specific treatment-related adverse events for each dose group. AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment. TRAEs are any event that occurs after the subject has received study treatment. AE grading will be performed in accordance with NCI-CTC Version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective responses rate (ORR) | Baseline through study completion, an average of 12 months | ORR is defined as the proportion of subjects with confirmed CR or confirmed PR. Radiologic assessment will be repeated after every second cycle (or more frequently if clinically indicated) and using same methodology as at baseline. Response assessment (radiologic) will be determined in accordance with RECIST (version 1.1) and current disease specific solid tumour response criteria. |
| Duration of response (DoR) | Baseline through study completion, an average of 12 months | DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first. |
| Disease Control Rate (DCR) | Baseline through study completion, an average of 12 months | Rate of patients who achieve either a Complete Response (CR) or a Partial Response (PR) or Stable Disease (SD) at Week 6 and Week 14 |
| Progression-free survival (PFS) | Baseline through study completion, an average of 12 months | PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST Version 1.1). |
| Overall survival (OS) | Baseline through study completion, an average of 12 months | OS defined as the time from the first dose to death from any cause. |
Countries
Belgium, France, Netherlands
Contacts
CONTACTTimothy Perera, PhD
CONTACTDesirée Kanters
STUDY_CHAIRJaap Verweij, MD
CMO DeuterOncology
Outcome results
None listed