Case Study Highlights Tumor Burden Reduction With Paxalisib Combo in Metastatic TNBC

Treatment with the novel pan-PI3K/mTOR inhibitor paxalisib in combination with immunotherapy and chemotherapy led to an 86% reduction in tumor burden in a patient with metastatic triple-negative breast cancer (TNBC), according to data derived from an expanded-access program for the regimen.1

The 86% reduction was observed on imaging following 3 weeks of treatment with the combination. The patient, who was over 40 years of age, was initially diagnosed in 2023, when she was treated with neoadjuvant chemotherapy and immunotherapy, followed by bilateral mastectomy 6 weeks after treatment; no residual cancer was detected after surgery, and the patient received subsequent radiation therapy. Metastatic disease to the bone and lungs was diagnosed approximately 2 years later, when the patient was treated under a single-patient expanded-access protocol.

"Although this is a single-patient expanded-access case, the speed and magnitude of tumor regression are highly encouraging and align with our scientific rationale for combining paxalisib with immune checkpoint blockade," John Friend, MD, chief executive officer of Kazia Therapeutics, stated in a news release. "This experience reinforces our commitment to our ongoing, company sponsored phase 1b trial [ACTRN12624001340527] in advanced breast cancer, and it echoes the recent ex vivo findings showing disruption of circulating tumor cell clusters with paxalisib."

How Is the Phase 1b Trial Evaluating Paxalisib?

Paxalisib-based combinations are currently being evaluated in the phase 1b study in patients with advanced breast cancer, including TNBC. The study is investigating paxalisib given in combination with olaparib (Lynparza; Arm A), as well as paxalisib plus pembrolizumab (Keytruda) and chemotherapy (Arm B).1,2

The study is enrolling patients at least 18 years of age inclusive; to be included in Arm A, patients need to have HER2-negative stage IV breast cancer with a confirmed germline BRCA mutation who received prior treatment with chemotherapy in the metastatic setting.2 In Arm B, patients need to have recurrent, unresectable or metastatic TNBC with a confirmed PD-L1 combined positive score of at least 10 who had no prior PD-1/PD-L1 therapy. All patients are required to have a life expectancy over 12 weeks, at least 1 confirmed measurable lesion per RECIST 1.1 criteria (or iRECIST criteria for Arm B), and an ECOG performance status of 0 or 1.

In Arm A, patients are being assigned to cohort 1 or cohort 2, where they are receiving the following regimens:

• Cohort 1: paxalisib at 15 mg once per day plus olaparib at 300 mg twice per day in 28-day cycles, with treatment continued for up to 12 months
• Cohort 2: paxalisib at 30 mg once per day plus olaparib at 300 mg twice per day in 28-day cycles for up to 12 months

Arm B also features 2 cohorts, where patients are receiving the following:

• Cohort 1: paxalisib at 15 mg once per day in 21-day cycles, pembrolizumab at 200 mg on day 1 of each cycle, and chemotherapy comprising nanoparticle albumin-bound paclitaxel, or gemcitabine/carboplatin per standard of care. Treatment is given for up to 12 months
• Cohort 2: paxalisib at 30 mg once per day in 21-day cycles, pembrolizumab at 200 mg on day 1 of each cycle, and chemotherapy comprising nanoparticle albumin-bound paclitaxel, or gemcitabine/carboplatin per standard of care. Treatment is given for up to 12 months

Safety and tolerability are serving as the trial’s primary end point. Secondary end points include circulating tumor cells, immune signature, progression-free survival, overall response rate, clinical benefit rate, duration of response, time to response, time to progression, and overall survival.

References

1. Kazia Therapeutics announces 86% reduction in tumor burden in expanded-access case of metastatic TNBC patient treated with paxalisib-immunotherapy regimen. News release. Kazia Therapeutics. October 2, 2025. Accessed October 3, 2025. https://finance.yahoo.com/news/kazia-therapeutics-announces-86-reduction-123000562.html
2. Paxalisib plus olaparib or pembrolizumab/chemotherapy in advanced breast cancer. ANZCTR. Updated June 7, 2025. Accessed October 3, 2025. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388489&isReview=true