Study of IK-595 in RAS- or RAF-altered Advanced Tumors

This is a Phase 1, FiH clinical study to evaluate the safety, tolerability, PK and pharmacodynamic effects, and preliminary anti-tumor activity of IK-595, a dual mitogen-activated protein kinase kinase (MEK)/ RAF kinase inhibitor, administered orally (PO) as monotherapy in patients with advanced solid tumors with gene alterations in the RAS- MAPK pathway for whom there are no further treatment options known to confer clinical benefit. The study consists of an initial Dose Escalation phase using a Bayesian Optimal Interval (BOIN) design, followed by a Dose Expansion phase in 4 genetically/molecularly defined cohorts using 2-stage adaptive design. During the Dose Escalation phase, backfilling may occur, where ≥ 3 additional patients can be enrolled at a given dose level once that dose level is deemed safe and tolerable by the Safety Review Committee. Backfilling includes, but is not limited to, patients with the following diagnoses: neuroblastoma RAS viral oncogene homolog-mutant (NRASmut) colorectal carcinoma (CRC), NRASmut malignant melanoma , Kirsten rat sarcoma viral oncogene homolog-mutant (KRASmut) CRC, KRASmut pancreatic cancer, KRASmut non-small cell lung cancer(NSCLC), B-Raf proto-oncogene, serine/threonine kinase-mutant (BRAFmut) Class II/III or BRAF fusion positive solid tumors, and Raf-1 proto-oncogene, serine/threonine kinase-mutant (CRAFmut) or fusion positive solid tumors. Various dose levels and schedules will be explored.