A first-in-human Phase i trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma

John De Groot, Martina Ott, Jun Wei, Cynthia Kassab, Dexing Fang, Hinda Najem, Barbara O'Brien, Shiao Pei Weathers, Carlos Kamiya Matsouka, Nazanin K. Majd, Rebecca A. Harrison, Gregory N. Fuller, Jason T. Huse, James P. Long, Raymond Sawaya, Ganesh Rao, Tobey J. Macdonald, Waldemar Priebe, Michael Decuypere, Amy B. Heimberger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-Arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. Results: In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T1/2 was 2-3 h with a dose dependent increase in the Cmax. Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. Conclusion: Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.

Original languageEnglish (US)
Article numberCNS87
JournalCNS oncology
Issue number2
StatePublished - Jun 2022


  • Glioblastoma
  • Phase I
  • STAT3 inhibitor
  • Toxicity

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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