Sacituzumab govitecan-hziy

Paxalisib produced clinical benefit across all six evaluable patients with Stage IV triple-negative breast cancer (TNBC) in an ongoing Phase Ib study. The molecule is a PI3K/mTOR inhibitor being developed by Australia-based Kazia Therapeutics Limited (Nasdaq: KZIA). Five of the six patients achieved an objective response — defined as a 30% or greater reduction in tumor burden — including one complete metabolic response and four partial responses, for an objective response rate of 83%. The sixth patient achieved stable disease. No paxalisib-related serious adverse events were observed, and no grade 3 or higher hyperglycemia, stomatitis, or mucositis occurred, toxicities that frequently limit PI3K/mTOR pathway inhibitors. Paxalisib inhibits both PI3K and mTOR, disrupting downstream signaling that drives tumor cell proliferation and, the company asserts, suppressing immune evasion mechanisms that render TNBC refractory to checkpoint inhibitor therapy. The trial evaluates paxalisib in combination with Merck's Keytruda (pembrolizumab) and chemotherapy in patients with advanced metastatic TNBC. The clinical responses were accompanied by exploratory translational findings. Across all six patients, terminally exhausted CD8+ T cells — a dysfunctional cytotoxic T-cell population that has lost anti-tumor activity — declined by a median of 51% within approximately three weeks of treatment, while total CD8+ T cell counts remained unchanged. Kazia said the finding may indicate a shift away from terminal T-cell exhaustion, while total CD8+ T-cell counts remained stable. Circulating tumor cell (CTC) clusters, which are associated with metastatic seeding, fell by a median of 83% within six to seven weeks. The company said blood-based multimodal protein, RNA, and plasma profiling showed increases in immune cell populations associated with anti-tumor activity alongside evidence of PI3K-AKT pathway target engagement. The most striking individual outcome involved a 44-year-old woman with Stage IV TNBC who achieved a complete metabolic response with no evidence of disease since November 2025 — a response that has remained durable through the most recent assessment. Responses were observed across lung, liver, bone, lymph node, and central nervous system target lesions, with responses emerging as early as approximately three months post-randomization. These results build on a series of earlier interim updates from the same trial. In January 2026, Kazia reported two partial responses and one complete metabolic response across three evaluable patients. The company expanded planned enrollment from 12 to 36 patients in May 2026, citing encouraging safety and tolerability data. The competitive context for post-immunotherapy metastatic TNBC is sparse. Gilead's Trodelvy (sacituzumab govitecan) is approved for patients who have received two or more prior systemic therapies, and Daiichi Sankyo and AstraZeneca's Datroway (datopotamab deruxtecan) received FDA approval in May 2026 for first-line immunotherapy-ineligible patients. Neither agent is specifically positioned for patients who have progressed on checkpoint inhibitor therapy, which is the population enrolled in the Kazia trial. Complete response rates with approved agents in metastatic TNBC are generally reported at 2–4%, according to Kazia's own November 2025 business update, making the one complete response observed here — in a single-digit patient cohort — an early data point that warrants scrutiny as enrollment expands. The Phase Ib trial is expected to complete enrollment by July 2027. Interim updates are anticipated throughout 2026 and 2027. Paxalisib holds Fast Track Designation from the US FDA for glioblastoma, where a Phase II/III readout in 2024 showed a clinically meaningful improvement in overall survival in a prespecified secondary analysis for newly diagnosed unmethylated patients, though the primary endpoint was not met on the cumulative control comparison. Regulatory discussions for that indication remain ongoing. The six-patient dataset is too small to draw efficacy conclusions, and the trial lacks a control arm at this stage. Spot something wrong? Report an issue with this article

The European Commission has approved Trodelvy (sacituzumab govitecan) in combination with pembrolizumab for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and whose tumors express PD-L1 with a combined positive score (CPS ≥10). The decision makes the regimen the first antibody-drug conjugate (ADC) plus immunotherapy combination approved in first-line metastatic TNBC across the EU's 27 member states, Norway, Iceland, and Liechtenstein. The combination approval follows a recent EC decision permitting Trodelvy monotherapy for first-line metastatic TNBC patients who are not candidates for PD-1 or PD-L1 inhibitor therapy. Together, Gilead Sciences (Nasdaq: GILD) said, the two approvals position Trodelvy as the backbone treatment for first-line metastatic TNBC regardless of PD-L1 status in Europe. The combination approval is based on the Phase III ASCENT-04/KEYNOTE-D19 trial, which evaluated Trodelvy plus pembrolizumab against standard-of-care chemotherapy plus pembrolizumab as first-line treatment in PD-L1-positive metastatic TNBC. The study reported a statistically significant improvement in progression-free survival, with Trodelvy demonstrating a 35% reduced risk of disease progression or death compared with the chemotherapy-based control arm, Gilead said. Trodelvy targets Trop-2, a cell surface antigen highly expressed across multiple tumor types, using a hydrolyzable linker to deliver SN-38, a topoisomerase I inhibitor payload. The design enables cytotoxic activity in Trop-2-expressing cells and in adjacent tumor cells through a bystander effect; this is combined with pembrolizumab's PD-1 checkpoint blockade. The EU approval broadens competition among TROP2-directed ADCs in first-line metastatic TNBC. Datroway, developed by AstraZeneca and Daiichi Sankyo, was approved in July 2026 for patients who are not candidates for PD-1/PD-L1 inhibitor therapy, while Trodelvy now spans both PD-L1-positive patients eligible for pembrolizumab and patients unsuitable for checkpoint inhibition. Further competitive pressure may emerge from sacituzumab tirumotecan, a next-generation TROP2 ADC from Kelun-Biotech and Merck & Co., which met its primary endpoint in a Phase III first-line TNBC trial. Notably, the same Trodelvy plus pembrolizumab combination did not succeed in non-small cell lung cancer. Gilead has indicated US FDA decisions on Trodelvy in first-line metastatic TNBC, based on the ASCENT-03 and ASCENT-04 trials, are anticipated. Spot something wrong? Report an issue with this article