taselisib (GDC-0032)

Specifically, the high-risk group exhibited increased immune cell infiltration, lower IC50 values for several drugs including 5-fluorouracil, afatinib, crizotinib, cediranib, taselisib, and staurosporine; Whereas the low-risk group displayed reduced stromal component proportions and better responses to entinostat, irinotecan, KRAS inhibitors, cisplatin, axitinib, and topotecan. The lactylation-m6A related prognostic model exhibited robust predictive efficiency in HCC. TCOF1 and HDAC1 may be promising tumor biomarkers for HCC and more researches are needed to validate these results.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

Taselisib reversed FAM64A-induced EMT and malignant phenotypes. FAM64A drives BLCA progression via PI3K/mTORC2/AKT-mediated EMT, serving as a potential prognostic biomarker and therapeutic target for metastatic BLCA.

Our findings suggest efficacy of PI3K inhibition + tamoxifen beyond second-line treatment and after prior targeted therapies, including CDK4/6 inhibition in metastatic HR+/HER2- breast cancer although the magnitude of benefit did not outweigh the tolerability of this combination. Exploratory biomarker analysis indicates that tumor fraction determined in ctDNA differentiates patients based on prognosis and may help to optimize patient selection for targeted treatment strategies.

The PI3K inhibitors GDC-0032 and INK1117 for PI3K-α and AZD8186 for PI3K-β are now being studied in clinical trials. Research on the clinical development, therapeutic utility, and structural insights of new PI3K inhibitors is the main emphasis of this review. The inhibitors have been shown promising anticancer activity relationships.

P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

The CONFIRM study (Phase 3 study comparing fulvestrant 250 vs. 500 mg) was used for model development, and the PALOMA-3 and SANDPIPER Phase 3 studies (palbociclib and taselisib) were used for external model qualifications. The TGI-OS model showed large underestimation for the OS for PALOMA-3; nevertheless, the predicted treatment effect (hazard ratio of OS) was in good agreement with the observation for both studies, suggesting its potential as a tool to support drug development decisions. While integrating shared clinical trial data from multiple sources, facilitated by platforms like Vivli, is crucial for advancing predictive modeling efforts, caution should be exercised when such models are applied for new studies, especially when there are breakthroughs in the treatment landscape.

Seven robust meta-programs (MP1-MP7) were identified in gastric cancer. MP7 was strongly correlated with cancer metastasis and poor survival of gastric cancer patients. MP7 promoted fibroblast transformation into myCAFs via GDF15/TGFBR2, creating an immune lockdown microenvironment. MyCAFs induced MP7 transformation via the RSPO3/EGR1 pathway, promoting gastric cancer cell migration. Taselisib and Lapatinib were potent inhibitors of MP7 GC cells.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P1, N=68, Completed, Otto Metzger, MD | Active, not recruiting --> Completed

P1, N=79, Completed, Royal Marsden NHS Foundation Trust | Unknown status --> Completed

P1, N=674, Terminated, Genentech, Inc. | Phase classification: P1/2 --> P1 | Completed --> Terminated; The Sponsor discontinued the manufacturing and development of taselisib due to modest clinical benefit and limited tolerability.