Preliminary Clinical Activity Observed With Paxalisib in R/R PCNSL


With over half of the patients enrolled in the phase 2 trial evaluating paxalisib in relapsed/refractory primary central nervous system lymphoma, some partial responses and stable disease have already been seen.

Lymphomas: © immimagery -

Lymphomas: © immimagery -

Clinical activity has been seen in patients with relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL), including partial responses and stable disease when treated with paxalisib (GDC-0084) monotherapy, according to a preliminary update from an ongoing investigator-initiated phase 2 trial (NCT04906096).1

Early clinical activity was observed in some patients; however, some patients experienced treatment-related adverse events (TRAEs) which were consistent with what has been previously observed among patients treated with paxalisib. This led to dose reductions and even early termination from the study in some of the enrolled patients.

As a result, investigators are optimizing the protocol and starting the doses administered to patients at 15 mg twice daily or 30 mg once daily. Their goal is to better the durability of clinical benefit and overall tolerability with paxalisib.

"We are encouraged by the clinical activity preliminarily observed to date and agree with the lead investigator to reduce the dose with the goal of improving tolerability and durability of response," stated John Friend, MD, chief executive officer of Kazia Therapeutics, in a press release.1 "The investigator has enrolled over half the patients needed to complete this study, and we look forward to receiving additional clinical updates in the future."

Background on the Phase 2 Study

In the open-label, phase 2 clinical trial, the efficacy of paxalisib in 25 patients with R/R PCNSL is being evaluated. The study is led by Lakshmi Nayak MD, of the Dana-Farber Cancer Institute in Boston, MA.1,2 To date, 14 patients have been enrolled in the study.

Those eligible for enrollment in the study are patients aged 18 years and older with R/R PCNSL, a Karnofsky Performance Status ≥ 70, histologically confirmed R/R primary diffuse large B-cellcentral nervous system lymphoma, and evidence of R/R disease on MRI with measurable or evaluable enhancing disease. Patients must have recovered to ≤ grade 1 or pre-treatment baseline from clinically significant adverse events before therapy, with the exception of patients with ≤ grade 2 neuropathy.

Additionally, patients must demonstrate adequate hematology and biochemistry and be able to undergo MRI. Patients with a dexamethasone requirement of ≤ 8mg/day or bioequivalent with corticosteroid usage at a stable or decreasing dose 2 weeks before the time of screening are also eligible for enrollment.

Patients will be administered paxalisib alone for up to 24 months, which will be given in an initial dosing regimen of 60 mg daily. This dosing regimen is similar to what has been used in other trials of paxalisib for the treatment of adult patients with brain cancer.

The primary end point of the study is objective response rate, with duration of response, progression-free survival, overall survival, and number of TRAEs as secondary end points. The estimated study completion date is May 1, 2025.2

About Paxalisib

Paxalisib is an investigational brain-penetrant inhibitor of the PI3K/ Akt /mTOR pathway. The agent is being developed for the treatment of patients with multiple forms of brain cancer.1

Previously in 2018, paxalisib was granted an orphan drug designation (ODD) from the FDA for patients with glioblastoma (GBM). This was followed by anFDA fast track designation(FTD) given to the agent for the treatment of patients with GBM in August 2020. Also in August 2020, paxalisib was granted rare pediatric disease designation and an ODD by the FDA for diffuse intrinsic pontine glioma, as well as for atypical teratoid and rhabdoid tumors in June 2022 and July 2022, respectively.

Additionally, paxalisib was awarded a FTD from the FDA in July 2023 for the treatment of solid tumor brain metastases harboring PI3K pathway mutations in combination with radiation therapy.

  1. Kazia Therapeutics provides preliminary update from ongoing phase 2 study of paxalisib in primary cns lymphoma. News release. Kazia Therapeutics Limited. November 1, 2023. Accessed November 2, 2023.
  2. Paxalisib (GDC-0084) in recurrent or refractory PCNSL. Updated July 5, 2023. Accessed November 2, 2023.
Related Videos
Related Content