{"id":2747,"date":"2026-08-27T10:00:00","date_gmt":"2026-08-27T14:00:00","guid":{"rendered":"https:\/\/www.insilens.com\/?p=2747"},"modified":"2026-08-28T16:38:06","modified_gmt":"2026-08-28T20:38:06","slug":"paxalisib-combination-shows-early-responses-in-tnbc","status":"publish","type":"post","link":"https:\/\/www.insilens.com\/?p=2747","title":{"rendered":"Paxalisib Combination Shows Early Responses in TNBC"},"content":{"rendered":"

Company:<\/strong> Kazia Therapeutics · Drug:<\/strong> Paxalisib · Combination:<\/strong> Paxalisib + Pembrolizumab + Chemotherapy · Indication:<\/strong> Metastatic Triple-Negative Breast Cancer · Date:<\/strong> August 27, 2026<\/p>\n

\"20260827_Kazia_Paxalisib_Therapeutic_Indications\"<\/p>\n

Summary<\/h4>\n

Kazia Therapeutics reported early efficacy signals from a small cohort of metastatic triple-negative breast cancer patients treated with paxalisib combined with pembrolizumab and chemotherapy, with five of six evaluable patients achieving objective responses and biomarker changes consistent with restored antitumor immune activity.<\/p>\n

What Happened<\/h4>\n

Among six evaluable metastatic TNBC patients, one achieved a complete response, four achieved partial responses, and one had stable disease, for an 83% objective response rate and 100% clinical benefit rate. A separate expanded-access patient has maintained an ongoing complete response since November 2025. Circulating tumor cell clusters fell 83% by weeks six to seven, and exhausted CD8 T-cell populations fell 51% by roughly week three. No paxalisib-related serious adverse events were reported.<\/p>\n

Deep Analysis<\/h4>\n

A six-patient, uncontrolled cohort is hypothesis-generating rather than confirmatory, and pembrolizumab-chemotherapy combinations already produce meaningful response rates in TNBC on their own, making paxalisib’s specific contribution difficult to isolate from this dataset alone. That said, the biomarker shifts, reduced circulating tumor cell clusters and reduced exhausted CD8 T-cell fractions, offer mechanistic plausibility that PI3K\/mTOR pathway inhibition is modulating the tumor immune microenvironment in a way that could complement checkpoint blockade. The clean early safety profile is also notable given paxalisib’s CNS-penetrant pharmacology. A larger, ideally randomized cohort would be needed to separate paxalisib’s contribution from the established backbone regimen.<\/p>\n

Company and Product Background<\/h4>\n

Kazia Therapeutics is an Australian oncology company. Paxalisib is a brain-penetrant, pan-PI3K\/mTOR inhibitor originally developed for glioblastoma, where it did not meet its primary endpoint in the GBM AGILE trial; the company has since repositioned the asset into combination immuno-oncology settings including triple-negative breast cancer.<\/p>\n

Signal Extraction<\/h4>\n\n\n\n\n\n\n\n
Factor<\/th>\nAssessment<\/th>\n<\/tr>\n
Cohort Size<\/td>\n6 evaluable patients, metastatic TNBC, uncontrolled<\/td>\n<\/tr>\n
Response Rate<\/td>\n83% ORR (1 CR, 4 PR), 100% clinical benefit rate<\/td>\n<\/tr>\n
Biomarkers<\/td>\n83% CTC-cluster reduction by Weeks 6-7; 51% exhausted CD8 T-cell reduction ~Week 3<\/td>\n<\/tr>\n
Safety<\/td>\nNo paxalisib-related serious adverse events reported<\/td>\n<\/tr>\n
Signal Type<\/td>\nEarly-stage combination oncology signal, small uncontrolled cohort<\/td>\n<\/tr>\n<\/table>\n

Reading the Signal<\/h4>\n

Bull case:<\/strong> The response rate and biomarker shifts in a hard-to-treat TNBC population, combined with a clean early safety profile, suggest the PI3K\/mTOR-immunotherapy combination could be reactivating antitumor immunity, an encouraging early signal for a drug that needed one after its glioblastoma trial failure.<\/p>\n

Bear case:<\/strong> An unblinded six-patient cohort without a comparator arm cannot establish causality or durable benefit, and TNBC responses to pembrolizumab-chemotherapy alone are well documented, so paxalisib’s incremental contribution is not yet isolated.<\/p>\n

InSilens Take<\/h4>\n

The data are a genuine green shoot for a drug that needed one after its GBM AGILE failure, but the sample size is far too small to change the risk profile; the next informative step is a larger, ideally randomized cohort that can isolate paxalisib’s contribution from the established chemoimmunotherapy backbone.<\/p>\n

Signal Assessment<\/h4>\n

Importance:<\/strong> 4\/5 · Direction:<\/strong> Uncertain · Confidence:<\/strong> Moderate on facts, Low on interpretation<\/p>\n","protected":false},"excerpt":{"rendered":"

Kazia Therapeutics reported early efficacy signals from a small cohort of metastatic triple-negative breast cancer patients treated with paxalisib combined with pembrolizumab and chemotherapy, with five of six evaluable patients achieving objective responses and…<\/p>\n","protected":false},"author":1,"featured_media":2758,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,3],"tags":[449,450,64],"class_list":["post-2747","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-clinical","category-therapeutic-indication","tag-kazia-therapeutics","tag-paxalisib","tag-triple-negative-breast-cancer"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/posts\/2747","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.insilens.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2747"}],"version-history":[{"count":1,"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/posts\/2747\/revisions"}],"predecessor-version":[{"id":2767,"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/posts\/2747\/revisions\/2767"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.insilens.com\/index.php?rest_route=\/wp\/v2\/media\/2758"}],"wp:attachment":[{"href":"https:\/\/www.insilens.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2747"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.insilens.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2747"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.insilens.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2747"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}