Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as PI3K Inhibitor paxalisib, [14C]-Paxalisib Capsule, Paxalisib (GDC-0084), GDC-0084
Paxalisib · 5 trials · 17 indications
The Objective Response (ORR) is defined as a complete, unconfirmed complete or partial response as determined by the investigator assessment using IPCG criteria
Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, NTRK/ROS, or KRAS G12C inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.
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.
| 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. |
| Arm I (CDK gene mutation) | EXPERIMENTAL | Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm II (PI3K gene mutation) | EXPERIMENTAL | Patients receive PI3K inhibitor paxalisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm III (NTRK/ROS1 gene mutation) | EXPERIMENTAL | Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm IV (KRAS G12C mutation) | EXPERIMENTAL | Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| 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. |
| Name | Type | Description |
|---|---|---|
| PAXALISIB | DRUG | Each study treatment cycle lasts 28 days, up to 24 months. Oral, daily, dosage per protocol |
| Abemaciclib | DRUG | Given PO |
| PI3K Inhibitor paxalisib | DRUG | Given PO |
| Entrectinib | DRUG | Given PO |
| Adagrasib | DRUG | Given PO |
| 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. |
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 in oncology for malignant primary gliomas, glioblastoma multiforme, primary central nervous system lymphoma, childhood cancers, and tumors with CDK gene mutations. It is in Phase 2 clinical development and has not been approved for any indication.
Paxalisib is a PI3K inhibitor. Its molecular targets include PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, and PIK3R2. By inhibiting these phosphoinositide 3-kinase subunits, the drug is designed to interfere with PI3K signaling, a pathway frequently altered in glioblastoma and other cancers.
Paxalisib is being developed by Kazia Therapeutics Limited, which trades under the ticker KZIA. The company is the sponsor of the clinical trials evaluating the drug in brain tumors and other malignancies.
Paxalisib is in Phase 2 clinical development. It is an investigational agent and has not received FDA approval. Trials of the drug have ranged from Phase 1 to Phase 2, with the Phase 2 studies focused on recurrent or refractory primary central nervous system lymphoma and genetic testing-guided treatment of brain metastases.
Paxalisib is being studied in several trials, including NCT07391215 (5G-PEARL in malignant brain tumors), NCT06208657 (precision therapies in childhood and adolescent cancer), NCT04906096 (Phase 2 in recurrent or refractory PCNSL), and NCT03994796 (genetic testing to guide treatment for brain metastases). All are recruiting or active.
Yes, Paxalisib is also known as GDC-0084. Other names used for the same compound include PI3K Inhibitor paxalisib and [14C]-Paxalisib Capsule. These refer to the same investigational PI3K inhibitor developed by Kazia Therapeutics.