Piqray (alpelisib)

P2, N=51, Active, not recruiting, GOG Foundation | Recruiting --> Active, not recruiting | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Apr 2025 --> May 2028

Using mouse models of ER+BC (FVB/N mice, TC11 tumor model), we show reduced growth of SEMA7A+ tumors with PI3K inhibitors (GCT-007:10 mg/kg daily, alpelisib: 20mg/kg daily), alone or in combination with tamoxifen (0.5mg/100uL, every 3rd day). Combination of an anti-SEMA7A antibody (SmAbH1) (100-250 ug/100uL, every other day) and fulvestrant (83 mg/kg, every 5 days) also revealed that direct inhibition of SEMA7A via SmAbH1 significantly reduces tumor growth of SEMA7A-expressing tumors, and that the efficacy of SmAbH1 is not diminished by the standard of care, fulvestrant. Overall, our studies suggest that patients with ER+SEMA7A+ tumors should be candidates for PI3K-targeted therapies or anti-SEMA7A-based therapy.

A sonic hedgehog (SHH)-MB model, including a Gorlin syndrome patient neuroepithelial stem cell line (NES) and its tumor derivative (tNES), was used to evaluate single and combined treatments of PI3K, AKT, FGFR, and CDK4/6 inhibitors (BYL719, AZD5363, JNJ-42756493, and PD-0332991, respectively). This study illustrates that single and combined administrations of PI3K, FGFR, CDK4/6, and AKT inhibitors in a NES/tNES model have dose-dependent and additive/synergistic anti-MB activity impacting tumor growth. Their effects on tNES cells were generally more pronounced than on NES; however, the difference in proliferative capacity between the cells should be considered.

P1/2, N=72, Recruiting, Novartis Pharma AG

P3, N=137, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2026 --> Jan 2027

Background: Evidence on the efficacy of alpelisib in combination with fulvestrant after progression on CKD4/6 inhibitors (CDK4/6i) is derived from a single non-comparative prospective study. Our results regarding the efficacy of alpelisib plus ET were inferior to those reported in the current literature. Conversely, outcomes of everolimus plus exemestane were consistent with the current literature, denoting that the combination is an acceptable treatment option for patients with PIK3CA-mutant metastatic BC.

P3, N=212, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2026 --> Mar 2027 | Trial primary completion date: Sep 2026 --> Jan 2027

This consensus uniquely contextualizes global evidence for GCC-specific healthcare constraints, addressing gaps in diagnostic access, affordability, and real-world feasibility, while providing treatment recommendations that help clinicians refine therapeutic strategies and incorporate patient preferences for improved outcomes. The panel recommends early genomic testing (PIK3CA, AKT, BRCA, ESR1) to guide therapy, prioritizing targeted agents such as oral SERDs and PI3K/AKT inhibitors in second-line sequencing, cautious use of alpelisib in diabetic patients, and incorporating patient preferences through shared decision-making and multidisciplinary care.

The pan-AKT inhibitor, Capivasertib (AZD5363), suppressed some but not all tested PIK3CA -mutated cell lines and one PIK3CA -wt cell line (SiHa). Further research on targeted therapies will improve the prognosis of patients with cervical cancer. Identified 3 molecular subtypes of CC based on PIK3CA and YAP1 amplification status Cervical cell lines with PIK3CA mutation are suppressed by targeted inhibitors PI3K inhibitors Alpelisib/Inavolisib selectively block PIK3CA-mutant cells PIK3CA mutation is associated with higher expression of the checkpoint CD274/PD-L1 PI3K inhibitors cooperate with donor-derived T cells to kill cervical cells.

Based on the findings, the patient opted for off-label therapy with alpelisib, an α-specific PI3K inhibitor that selectively targets p110α and has shown promising efficacy in breast cancer patients harboring the identical PIK3CA mutations. However, no clinical response was observed in the patient, and the lack of response may be associated with the specific nature of the PIK3CA mutation, and/or other unfavorable tumor biological factors that override any benefit from alpelisib.

P3, N=19, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

P=N/A, N=15, Completed, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's | Active, not recruiting --> Completed