Phase I Study of Rogocekib in Patients with Advanced, Relapsed, or Refractory Malignant Solid Tumors

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Aberrant RNA splicing is a key driver in cancer progression.
• Targeted therapies for aberrant splicing, like CDC2-like kinase (CLK) inhibitors, are needed.
• Rogocekib (CTX-712) is an oral CLK inhibitor designed to target RNA splicing.

Purpose of the Study:

• Evaluate the safety, tolerability, and maximum tolerated dose (MTD) of rogocekib in advanced solid tumors.
• Determine the recommended dose (RD) for further clinical trials.
• Assess the pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of rogocekib.

Main Methods:

• Phase I dose-escalation study using an accelerated titration followed by a 3+3 design.
• Doses ranged from 10 mg to 175 mg, administered twice weekly (BIW) or once weekly (QW).
• 46 patients with advanced solid tumors were enrolled.

Main Results:

• The MTD was established at 140 mg BIW.
• Common adverse events included nausea, vomiting, and diarrhea; two treatment-related deaths occurred.
• Rogocekib demonstrated dose-dependent PK, target engagement (PD markers THAP9-AS1, S6K), and preliminary efficacy (6.5% partial response, primarily in ovarian cancer).

Conclusions:

• Rogocekib shows target engagement and preliminary antitumor activity in solid tumors.
• Most toxicities were manageable, but safety monitoring is crucial due to observed treatment-related deaths.
• Further clinical investigation of rogocekib is warranted.