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.
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
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
Sequential
DO-2
DrugDeuterated MET kinase inhibitor
Number of subjects who experience specific treatment-related adverse events (TRAEs)
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.
Objective responses rate (ORR)
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)
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)
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)
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).
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