AACR 2017 | Poster CT038/14 – 204653 study design: a phase I, open-label, dose-escalation study of GSK3326595 in patients with Non-Hodgkin Lymphoma

This year’s American Association for Cancer Research (AACR) annual meeting took place on 1–5 April in Washington, DC, USA. The program committee Chair was Kornelia Polyak, MD, PhD, from the Dana-Farber Cancer Institute, Boston, Massachusetts.

On Monday 3^rd April, a poster (CT038 / 14) by Drew Rasco, from South Texas Accelerated Research Therapeutics, San Antonio, TX, et al. titled “A phase I, open-label, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of GSK3326595 in subjects with solid tumors and non-Hodgkin's lymphoma” was presented.

GSK3326595 is an orally administered, selective, and reversible Protein Arginine Methyltransferase 5 (PRMT5) inhibitor, which halts proliferation and induces apoptosis in numerous solid and hematologic tumor cell lines. It has been shown to have potent anti-tumor activity in vivo in animal models.

Key Highlights:

Design

• Two-part study design; Part 1 is a dose escalation in R/R solid tumors and Part 2 is a dose expansion in R/R solid tumors and NHL
• In Part 2, GSK3326595 will be given according to the Recommended Phase II Dose (RP2D) defined in Part 1
• Enrollment to Part 2 may potentially be halted if “low probability of exceeding historical control response rates is reached (i.e. futility)”

Enrollment criteria

• Gender: male or female
• Age: ≥18 years
• Disease measured per standard criteria (for Part 2)
• Part 2: metastatic or unresectable NHL; disease must have recurred or failed to respond to standard therapy

Present accrual

• Part 1
  • As of March 24 2017, no DLTs reported in first 4 dose levels of monotherapy
  • Enrollment for dose level 5 cohort is ongoing
  • Pk/PD cohort has been initiated
  • Open study sites (n = 10) in the US, Spain, Italy, France, The Netherlands, Australia, and Canada