Kazia Triples Down on Paxalisib in Aggressive Breast Cancer Trial

SYDNEY, Australia – May 26, 2026 – Kazia Therapeutics has announced a significant expansion of its clinical trial for paxalisib in patients with advanced triple-negative breast cancer (TNBC), tripling the planned enrollment from 12 to 36 patients. The move, driven by encouraging early data on the drug's safety and tolerability, signals growing confidence in its potential to tackle one of the most challenging forms of breast cancer.

The Phase 1b study is evaluating paxalisib, an investigational therapy, in combination with the standard-of-care immunotherapy drug pembrolizumab and chemotherapy. By increasing the number of participants, the Sydney-based oncology company aims to gather more robust data on the combination's effectiveness, dose optimization, and impact on patient outcomes.

"We remain encouraged by the safety and tolerability data observed to date, and expanding enrollment allows us to generate a broader clinical and translational dataset as we advance paxalisib in difficult-to-treat advanced breast cancer, such as TNBC," said Dr. John Friend, CEO, Kazia Therapeutics, in a statement. He emphasized the drug's unique mechanism, which he believes "holds meaningful potential for an underserved patient population."

A Calculated Bet Against an Aggressive Foe

The decision to expand the trial is a notable step in the fight against triple-negative breast cancer, a subtype that accounts for 15-20% of all breast cancer diagnoses. Unlike other breast cancers, TNBC tumors lack estrogen, progesterone, and HER2 receptors, rendering hormonal therapies and HER2-targeted drugs ineffective. This leaves patients with fewer treatment options, historically relying on broad-spectrum chemotherapy.

TNBC is known for its aggressive behavior, rapid growth, and higher likelihood of recurrence and metastasis compared to other subtypes. The prognosis for patients with metastatic TNBC remains poor, with median survival rates often falling under 18 months despite recent therapeutic advances.

The treatment landscape has evolved, with the introduction of immunotherapy like Merck’s Keytruda (pembrolizumab) for patients whose tumors express the PD-L1 protein, and powerful antibody-drug conjugates (ADCs) such as Gilead's Trodelvy and the recently approved Datroway from AstraZeneca and Daiichi Sankyo. However, a significant unmet need persists, particularly for patients who do not respond to or become resistant to these newer therapies. Kazia’s trial expansion suggests the company sees a potential role for paxalisib within this complex and competitive environment.

Targeting the Engine of Resistance

At the heart of Kazia's strategy is paxalisib's mechanism of action. The drug is a potent, brain-penetrant inhibitor of the PI3K/Akt/mTOR pathway, a critical signaling network that controls cell growth, survival, and metabolism. In a majority of TNBC cases, this pathway is hyperactivated, acting like a stuck accelerator pedal that drives uncontrolled cancer proliferation and, crucially, fosters resistance to both chemotherapy and immunotherapy.

Targeting this pathway is a well-established goal in oncology, but it has been fraught with challenges. First-generation inhibitors often struggled with significant side effects and limited efficacy as cancer cells found ways to reactivate the pathway through feedback loops.

Kazia's approach with paxalisib, a dual inhibitor of both PI3K and mTOR, aims to provide a more comprehensive shutdown of the pathway. The rationale is supported by a recently published preclinical study in Molecular Cancer Therapeutics, which demonstrated that paxalisib could alter the tumor cell state and immune signaling in TNBC models. This dual-action and its potential to modulate the tumor microenvironment could make cancer cells more vulnerable to accompanying treatments like chemotherapy and immunotherapy.

A Drug with a History and a Future

While the focus is now sharpening on breast cancer, paxalisib is not a new contender in oncology. Licensed from Genentech in 2016, its primary development has been in glioblastoma (GBM), the most aggressive form of primary brain cancer, where the PI3K pathway is almost universally activated. The drug’s ability to cross the blood-brain barrier—a formidable obstacle for many cancer therapies—makes it uniquely suited for central nervous system tumors.

After a long development journey that included a perceived setback in the GBM AGILE adaptive trial, final data reported in 2024 revealed a meaningful 3.8-month survival benefit for a specific group of newly diagnosed glioblastoma patients compared to the standard of care. The company is now in discussions with the U.S. Food and Drug Administration (FDA) about a potential pivotal study for approval.

Further bolstering its profile, paxalisib has shown remarkable preliminary results in other settings. In an ongoing study for brain metastases—cancer that has spread to the brain from other parts of the body—an interim analysis of nine patients treated with paxalisib and radiation showed a 100% objective response rate. The drug has also received multiple FDA special designations, including Fast Track and Orphan Drug status for glioblastoma and other rare cancers, acknowledging its potential to address serious unmet medical needs.

The Strategic Dance of Disclosure and Discovery

Adding a layer of intrigue to the company’s recent activities was the decision to withdraw its scientific abstracts from the upcoming 2026 American Society of Clinical Oncology (ASCO) annual meeting, a premier global cancer conference. Dr. Friend clarified that the move was made "solely to protect our intellectual property position ahead of anticipated filings" and was unrelated to any safety or clinical concerns.

This maneuver is a classic strategic play in the high-stakes world of biotechnology. Public disclosure at a scientific conference can constitute "prior art," potentially jeopardizing a company's ability to secure patents on novel discoveries. By holding its data close, Kazia is signaling that it believes its findings are valuable and warrant robust IP protection before being shared with the scientific community and competitors.

This cautious strategy aligns with the significant investor interest the company has garnered. Kazia’s stock (NASDAQ: KZIA) has surged over 280% in the past year, and it currently holds a "Strong Buy" consensus rating from analysts. Bolstered by a recent $50 million financing round, the company reports it is funded for planned operations into 2029. This financial stability gives it the runway to see its expanded TNBC trial through and carefully manage the disclosure of its increasingly promising data. The next series of clinical and translational updates, expected throughout 2026 and into 2027, will be closely watched by patients, clinicians, and investors alike.