Breakthrough Clinical Results

Kazia Therapeutics announced the publication of preclinical research in Molecular Cancer Therapeutics demonstrating paxalisib's potential to overcome immunotherapy resistance in triple-negative breast cancer (TNBC). The study, conducted by Professor Sudha Rao at QIMR Berghofer Medical Research Institute, showed paxalisib's ability to reprogram the tumor microenvironment, enhancing immune response and synergizing with immune checkpoint inhibitors. This supports the ongoing Phase 1b clinical trial evaluating paxalisib in combination with checkpoint inhibitors and chemotherapy in advanced breast cancer. The data suggests paxalisib could significantly improve treatment outcomes for this aggressive cancer subtype.

Emerging Mechanism of Action

Triple-negative breast cancer (TNBC) is a challenging subtype of breast cancer due to its aggressive nature and lack of targeted treatment options. However, recent research within the past three years has highlighted several emerging mechanisms of action (MoAs) and therapeutic strategies:

• Antibody-drug conjugates (ADCs): ADCs like fam-trastuzumab deruxtecan (T-DXd) have shown significant anti-tumor activity in HER2-low TNBC. T-DXd targets HER2, a protein often expressed at low levels in TNBC, and delivers a potent topoisomerase I inhibitor directly to cancer cells. The DESTINY-Breast04 trial demonstrated improved progression-free and overall survival with T-DXd compared to standard chemotherapy in HER2-low metastatic breast cancer, including TNBC. Other ADCs, such as sacituzumab govitecan, targeting Trop-2, have also shown promise in previously treated metastatic TNBC.

• Immunotherapy: Immunotherapy, particularly immune checkpoint inhibitors, has emerged as a promising treatment option. Combining checkpoint inhibitors like atezolizumab or pembrolizumab with chemotherapy has shown improved outcomes in PD-L1-positive advanced TNBC. Research is ongoing to understand the complex interplay between the tumor microenvironment and immune response in TNBC, and to identify predictive biomarkers for immunotherapy response.

• Targeting specific molecular pathways: Researchers are exploring various molecular pathways involved in TNBC development and progression. PARP inhibitors, such as olaparib and talazoparib, have shown efficacy in germline BRCA-mutated TNBC. Other potential targets include AKT, PI3K, and androgen receptors. Further research is needed to identify optimal patient populations for these targeted therapies.

• Nanoparticle-based therapy: Nanotechnology offers potential solutions for improving drug delivery and reducing toxicity. Nanoparticles can be engineered to deliver chemotherapeutic agents or other targeted therapies directly to tumor cells, enhancing efficacy and minimizing side effects. This approach is still under investigation, but holds promise for improving TNBC treatment.

• Addressing the tumor microenvironment: The tumor microenvironment plays a crucial role in TNBC progression and therapy resistance. Tumor-associated macrophages (TAMs), for example, can promote tumor growth and suppress anti-tumor immune responses. Strategies to modulate TAM activity or target other components of the tumor microenvironment are being explored.

In summary, while chemotherapy remains a cornerstone of TNBC treatment, several novel MoAs are emerging, offering hope for improved outcomes. ADCs, immunotherapy, targeted therapies, and nanotechnology-based approaches are showing promise in preclinical and clinical studies. Further research is needed to refine these strategies, identify predictive biomarkers, and develop personalized treatment approaches for TNBC patients.

Drug used in other indications

The provided text focuses on trials of buparlisib for triple-negative breast cancer and does not mention other indications for which it is being trialed.

One study evaluated buparlisib in patients with metastatic triple-negative breast cancer. This was a single-arm phase 2 study where patients received buparlisib at a starting dose of 100 mg daily. The primary endpoint was clinical benefit, defined as confirmed complete response (CR), partial response (PR), or stable disease (SD) for ≥ 4 months. The clinical benefit rate was 12% (6 patients, all SD ≥ 4 months). Median PFS was 1.8 months and median OS was 11.2 months. The most frequent adverse events were fatigue, nausea, hyperglycemia, and anorexia. Some patients also experienced depression and anxiety.

Company drugs approved in other indications

Based on the provided medical research abstracts, there is no information about Kazia Therapeutics Limited or what indications they have drug approvals for, other than possibly Mebendazole (MBZ) for Triple-Negative Breast Cancer (TNBC). The abstracts discuss various treatments for TNBC, including chemotherapy, PARP inhibitors, immunotherapy, and repurposed drugs like MBZ.

Specifically, one abstract mentions MBZ, an FDA-approved anthelmintic, being repurposed for TNBC and other cancers. It notes MBZ's low toxicity in humans and efficacy in preclinical cancer models, including TNBC. However, this abstract does not mention Kazia Therapeutics Limited. Therefore, it's impossible to determine from the provided text whether Kazia is involved in MBZ's development for TNBC or any other indications.

To find information about other indications Kazia Therapeutics Limited may have drugs approved for, you would need to consult additional resources such as the company's website, press releases, or regulatory agency databases.