NCT04933422

CM93 Treatment in Subjects With Epidermal Growth Factor Receptor (EGFR)-Modified Recurrent Glioblastoma (rGBM)

Phase 1 Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Effects of CM93 in Subjects With Recurrent Glioblastoma (rGBM) Characterized by Epidermal Growth Factor Receptor (EGFR) Mutation or Amplification

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: Crimson Biopharm Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a first-in-human study of CM93, an oral investigational drug, in adults with Epidermal Growth Factor Receptor-modified glioblastoma. The study is designed in three parts consisting of a dose-escalation phase, a dose-expansion phase and a window-of-opportunity surgical trial. The trial objectives are to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical effects of CM93 in this patient population.

Detailed description

CM93 is a third-generation, covalent/irreversible, brain penetrant small molecule Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor. It is not a substrate of p-glycoprotein or breast cancer resistance protein (bcrp) and is a mild inhibitor of bcrp. It is a potent inhibitor of EGFR mutations but also has activity against wild type EGFR. This first-in-human phase I trial will evaluate the safety, tolerability, and pharmacokinetics (PK) of CM93 and determine the recommended Phase 2 dose (RP2D) for further evaluation using a 3+3 design (Part 1). Once the RP2D has been determined 12 additional patients will be treated in a dose expansion cohort to confirm the safety and tolerability of the selected dose (Part 2). Subsequent to the phase I trial a window-of-opportunity surgical trial will initiate. Tumor from both contrast enhancing and non-contrast enhancing areas of patients who received CM93 before surgery will be resected and evaluated to determine if therapeutic concentrations of the drug are achieved. Pharmacodynamic studies will be conducted in tumor tissue from patients who received CM93 before surgery and the patients who did not receive drug before surgery to determine if there is adequate inhibition of EGFR. After recovery from surgery all 30 patients will receive CM93 until progression, development of unacceptable toxicity, or withdrawal of consent and preliminary evidence of activity will be obtained.

Conditions

• Glioblastoma

Interventions

Type	Name	Description
DRUG	CM93	oral capsule of CM93 administered once daily

Timeline

• Start date: 2027-01-01
• Primary completion: 2029-07-01
• Completion: 2029-07-01
• First posted: 2021-06-21
• Last updated: 2024-08-21

Regulatory

• FDA-regulated drug study