Abstract 602TiP
Background
TRK family proteins (Trk A, B and C) are constitutively activated in certain malignancies of both children and adults, especially when chimeric proteins involving tyrosine kinase portion are produced by rearrangements of NTRK 1, 2 or 3 genes. A number of small molecule inhibitors of TRK proteins have been developed and tried in clinical trials, some of which are now approved in an accelerated pathway. Cases of primary or secondary resistance to such drugs are accumulating, so a new drug with broader activity and improved pharmacologic features is still warranted. NOV1601 (CHC2014) is a novel small molecule of oral route of administration, with unique dynamic configurations in relation to solvent-front mutants of TRK proteins. Non-clinical studies suggested potential of NOV1601 (CHC2014) to overcome primary or secondary resistance to the already approved TRK inhibitor.
Trial design
This is the first-in-human, phase I, open-label, multicenter, dose-escalation study to investigate the safety, tolerability, PK, and clinical activity of NOV1601 in subjects with solid organ malignancies at four research-based hospitals in the Republic of Korea. The primary objective is to determine the recommended phase II dose (RP2D) of NOV1601 in adult subjects with solid organ malignancies. Dose escalation will follow a 3+3 design and will be based on prior cohort review. NOV1601 will be administered orally once daily (QD) or twice daily (BID) doses for continuous 28-day cycles. To date, 7 patients were enrolled and administered at 50mg QD or 100mg QD. NOV1601 is currently being administered at 150mg QD. The maximum tolerated dose (MTD) is not pre-determined yet. If MTD is not reached because of no dose-limiting toxicity, then the RP2D will be determined by PK and safety profiles. Efficacy per RECIST convention will be measured as an exploratory endpoint, and special attention will be cast to subjects with known genetic alterations involving NTRK family genes. Such cases will be validated at a central pathology laboratory using multiple diagnostic technologies available. Currently, this study is ongoing with affirmative PK and safety profiles as had been expected from non-clinical studies.
Clinical trial identification
NCT04014257.
Editorial acknowledgement
Legal entity responsible for the study
HANDOK INC. & CMG Pharmaceutical Inc. & National OncoVenture.
Funding
HANDOK INC. & CMG Pharmaceutical Inc. & National OncoVenture.
Disclosure
All authors have declared no conflicts of interest.