Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PAXALISIB · 5 trials · 11 indications
The Objective Response (ORR) is defined as a complete, unconfirmed complete or partial response as determined by the investigator assessment using IPCG criteria
A DLT was defined as a Grade 3 or 4 toxicity occurring within the DLT assessment window and assessed to be probably or possibly related to paxalisib. DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. CTCAE Grade 3 is a severe adverse event (AE) and Grade 4 is a life-threatening or disabling AE. DLTs were collected to determine the maximum tolerated dose (MTD), which was defined as the dose level below the dose at which less than 33% of participants experienced a DLT.
To identify the incidence, nature and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v5.0
Antitumour activity will be defined on the basis of the following outcomes. If any of the following occur, patients will be considered to have clinically benefitted: For front line unmethylated GBM (MRD): • Progression-free survival (PFS)
Antitumour activity will be defined on the basis of the following outcome: • Progression-free survival (PFS), defined as the time from enrolment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RANO
Number of CAYA participants (children, adolescents and young adults) with advanced solid tumours (including CNS tumors and non-Hodgkin lymphomas) where molecular sequencing data was used to allocate treatment arms of molecularly-targeted agents.
Recommended phase II dose of a novel single agent or combination treatment in CAYA participants, determined by dose-limiting toxicities reported as per CTCAE V5.0.
ORR defined as complete response and partial response, as measured by RECIST, RAPNO, INRC or RECIL in CAYA participants treated with molecularly-targeted agents.
Mass balance recovery of total radioactivity (TR) in all excreta (urine and faeces): CumAe (amount excreted) and Cum%Ae
Collection of plasma samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites
Collection of urine samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites
Collection of faecal samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites
| Arm | Type | Description |
|---|---|---|
| PAXALISIB | EXPERIMENTAL | The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits. * Paxalisib (GDC-0084) * Each study treatment cycle lasts 28 days, up to 24 months. |
| Dose Escalation and Expansion Cohorts | EXPERIMENTAL | This is an open-label study. Patients in Stage 1 will be enrolled and sequentially assigned to a dose cohort. The initial cohort will receive an oral dose of 60 mg paxalisib QD (4 x 15 mg capsules). Patients of future dose cohorts will receive paxalisib at increasing levels with 15 mg steps until a dose-limiting toxicity occurs (DLT) occurs. The dose level where \<1/3 of the patients exhibit a DLT will be determined the Maximum Tolerated Dose (MTD). In stage 1, dose escalation will occur for QD dosing. In stage 2, the expansion phase, patients will receive doses of oral paxalisib at the MTD in stage 1, until disease progression or an unacceptable toxicity, whichever occurs first. Patients will be randomized in a 1:1 ratio to fed or fasted schedules. |
| Phase 1b | EXPERIMENTAL | The Phase 1b will evaluate the safety and tolerability of paxalisib in combination with temozolomide and determine their preliminary antitumour activity in patients with molecularly defined malignant brain tumours. |
| Phase 2 | EXPERIMENTAL | The Phase 2 part of the study will determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours. |
| Arm A Paxalisib | EXPERIMENTAL | Drug: Irinotecan, Drug: Temozolomide, Drug: Paxalisib. Irinotecan starting at 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles. Temozolomide starting at 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles. Paxalisib starting at 21mg/m2 oral, daily, 28 day cycle, 13 cycles. |
| Arm C Opdualag | EXPERIMENTAL | Drug: Opdualag, a fixed dose combination of Nivolumab and Relatlimab Opdualag, a fixed-dose combination of Nivolumab 480mg and Relatlimab 160mg, intravenous, on day 1, 28 day cycle, 26 cycles. |
| [14C]-Paxalisib Capsule | EXPERIMENTAL | Subjects will be dosed on the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects will remain resident in the clinical unit until 168 h post dose (Day 8) and this may be extended up to a maximum of 48 h (i.e., up to Day 10). |
| Name | Type | Description |
|---|---|---|
| PAXALISIB | DRUG | Each study treatment cycle lasts 28 days, up to 24 months. Oral, daily, dosage per protocol |
| Paxalisib (GDC-0084) | DRUG | Patients will be dosed orally with paxalisib (GDC-0084) capsules (15-mg each) at the dose and schedule to which they are assigned. |
| Temozolomide capsule | DRUG | Temozolomide will be supplied as 5, 20, 100, 140, 180 or 250 mg hard capsules. |
| Opdualag | DRUG | Opdualag, a fixed-dose combination of Nivolumab 480mg and Relatlimab 160mg, intravenous, on day 1, 28 day cycle, 26 cycles |
| Irinotecan (drug) | DRUG | Irinotecan starting at 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles. |
| Temozolomide (TMZ) | DRUG | Temozolomide starting at 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles. |
| [14C]-Paxalisib Capsule | DRUG | Each subject will receive a single dose 15 mg (NMT 3.5 MBq), administered orally in the fasted state with with 240 mL water. |
Inclusion Criteria: * Participants must be able to understand and willing to sign a written informed consent document. * Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before ...
Paxalisib is an investigational small molecule being studied for multiple oncology indications, including glioblastoma, malignant primary gliomas, primary central nervous system lymphoma, and childhood cancers. It is also being evaluated in healthy volunteers for a mass balance study. The drug is not approved and remains in clinical development.
Paxalisib targets PI3K, as indicated by its drug class of -lisib (PI3K) inhibitors. It is being studied as a potential treatment for brain cancers and other malignancies where PI3K pathway signaling may play a role in tumor growth.
Paxalisib is being developed by Kazia Therapeutics Limited, an Australian biopharmaceutical company listed on the NASDAQ under the ticker symbol KZIA. The company is conducting clinical trials of paxalisib across multiple oncology indications.
Paxalisib is in Phase 2 clinical development. It has received FDA designations including Orphan Drug, Fast Track, and Rare Pediatric Disease designations. The drug is investigational and has not been approved by regulatory authorities.
Paxalisib is being studied in several clinical trials, including NCT04906096 for recurrent or refractory primary central nervous system lymphoma, NCT05012670 in healthy volunteers, NCT06208657 for childhood cancers, and NCT07391215 for malignant brain tumors including glioblastoma.
Yes, paxalisib is also known as GDC-0084, as indicated in the clinical trial title for the primary central nervous system lymphoma study. This alternative name may appear in older literature or trial registrations.