NCT06270082

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

A First-in-Human (FiH) Study of IK-595, an Oral Dual MEK/RAF Inhibitor, in Patients With RAS-or RAF-altered Advanced Solid Tumors

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: Ikena Oncology · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1, FIH, Dose Escalation and Dose Expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) effects, and preliminary antitumor activity of IK-595, a MEK/RAF molecular glue, administered orally 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.

Detailed description

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.

Conditions

• Solid Tumor, Adult
• Colorectal Cancer
• Pancreatic Cancer
• Malignant Melanoma
• Ras (Kras or Nras) Gene Mutation
• BRAF Gene Mutation
• CRAF Gene Mutation
• Non-Small Cell Lung Carcinoma
• Thyroid Carcinoma
• Gliomas, Malignant

Interventions

Type	Name	Description
DRUG	IK-595	Oral tablet administered in 28-day or 30-day cycles until treatment discontinuation criteria are met.

Timeline

• Start date: 2023-12-18
• Primary completion: 2025-09-08
• Completion: 2025-09-08
• First posted: 2024-02-21
• Last updated: 2025-09-19

Locations

15 sites across 1 country: United States

Regulatory

• FDA-regulated drug study