P3, N=137, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> May 2025

P3, N=209, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=1, Terminated, Columbia University | Active, not recruiting --> Terminated; Enrollment challenges

The allosteric PI3Kα inhibitor STX-478 inhibits the growth of tumor with hotspot mutations in PI3Kα and shows prominent efficacy on the treatment of human HNSCC xenografts without displaying the metabolic dysfunction observed in Alpelisib. After the SciFinder verification, J-53 with novel structure had the value of further study. This study suggested that J-53 could be used as potential inhibitors of PI3Kα, and provides valuable information for the subsequent drug discovery of allosteric PI3Kα inhibitors.

P1, N=68, Active, not recruiting, Faeth Therapeutics | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025

P1, N=174, Recruiting, Risen (Suzhou) Pharma Tech Co., Ltd.

P1/2, N=8, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025

P3, N=27, Active, not recruiting, Spanish Breast Cancer Research Group | Trial completion date: Nov 2024 --> Jun 2025 | Trial primary completion date: Nov 2024 --> Jun 2025

PTEN presence, BCL2 mutations, and low or undetectable baseline IL-2 levels were associated with improved patient survival following treatment with C + R, supporting a potential role for these biomarkers in guiding treatment selection for patients with indolent non-Hodgkin lymphoma.

We have identified a signalling pathway of interest for the treatment of advanced ovarian cancer in vitro, which could limit the progression of this disease. These data pave the road to investigate whether PI3Kα-specific inhibitor BYL-719 should be proposed in combination with cisplatin, in priority in patients bearing a PIK3CA mutation.

Enhanced expression of ARNTL2 led to an elevation in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) phosphorylation within PTC cells, while the administration of alpelisib effectively mitigated the effects induced by upregulated ARNTL2 on EMT, PTC cell proliferation, apoptosis, and invasion. Elevated ARNTL2 levels enhance PTC proliferation, migration, invasion, and EMT while inhibiting apoptosis through the cell cycle signaling, elucidating its potential as a diagnostic PTC biomarker.

Finally, in both HA cell lines AKT kinase was hyperphosphorylated and the cells showed increased sensitivity to copanlisib, a pan-PI3K inhibitor...Increased dependence on BCL-XL and PI3K-AKT signaling for survival. In translation, inhibition of glycolysis, BCL-XL, or PI3K-AKT cascade may result in targeted elimination of HA lymphoma cells.

We established an ex vivo model to study alpelisib effects on Pten-deficient lipomas. These results underscore the therapeutic potential of targeted PI3K inhibition in the treatment of PHTS-associated lipomas, particularly in cases that are inoperable.

P3, N=230, Recruiting, Hoffmann-La Roche | Trial completion date: Jan 2028 --> Dec 2032

Actionable biomarkers, such as PIK3CA and ESR1 mutations, have emerged as pivotal tools to guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib and elacestrant and emphasizing the important role of biomarkers in guiding the selection of therapy. This overview aims to provide clinicians with a practical and up-to-date framework to inform treatment decisions and improve patient care in the context of this challenging disease. Additionally, we review emerging biomarkers and novel treatment strategies to address this difficult clinical landscape.

P2, N=188, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Simultaneously targeting the PI3K signaling pathway and exogenous FA uptake could potentially be advantageous for patients with PTEN-loss anti-HER2 resistant breast cancer.

Our results do not support the antitumor activity of single-agent copanlisib in tumors with PTEN loss regardless of mutation or deletion status or PTEN deleterious mutations with PTEN expression.

P1/2, N=102, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

These findings suggest the usefulness of NGS testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

P1, N=40, Recruiting, Hoffmann-La Roche | Trial completion date: Jun 2025 --> Aug 2026 | Trial primary completion date: Jun 2025 --> Mar 2026

P1, N=220, Not yet recruiting, Vividion Therapeutics, Inc.

However, the combination of copanlisib and afatinib completely blocked phosphorylation of the ErbB family (including HER3) and Akt, while also increasing apoptosis. In conclusion, these results suggested that co‑targeting the ErbB family kinases and PI3K using a combination treatment of afatinib and copanlisib may have clinical potential for patients with HPV‑negative HNSCC.

P2, N=66, Terminated, Breast Cancer Trials | Recruiting --> Terminated

Other notable adverse effects were rash, stomatitis, diarrhea, pneumonitis, reduced appetite, elevated liver enzymes, nausea, fatigue, and rare reports of diabetic ketoacidosis. This literature review aims to highlight the incidence and risk factors of alpelisib-induced hyperglycemia in greater depth.

P1, N=27, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Dec 2024 --> Jul 2025

P3, N=400, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1/2, N=50, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

On 10 October 2024, inavolisib received its first approval in the USA in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. In the EU and other countries worldwide, regulatory review of inavolisib is currently underway. This article summarises the milestones in the development of inavolisib leading to this first approval for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer.

P=N/A, N=4, Terminated, Novartis Pharmaceuticals | N=150 --> 4 | Trial completion date: Dec 2025 --> Oct 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Oct 2024; Low recruitment

P3, N=450, Not yet recruiting, Hoffmann-La Roche

P3, N=358, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2026 --> Jun 2025

P1/2, N=52, Not yet recruiting, Henan Cancer Hospital

P=N/A, N=103, Completed, Novartis Pharmaceuticals | Recruiting --> Completed | Trial completion date: Dec 2024 --> Jun 2024 | Trial primary completion date: Dec 2024 --> Jun 2024

The high prevalence of somatic alterations in TP53, PIK3CA, ESR1, and BRCA1/2 genes, identified by ctDNA genotyping, highlights their potential as biomarkers for targeted therapies. Detection of specific mutations affected treatment decisions, such as eligibility for alpelisib, and might further facilitate treatment with e.g. elacestrant or capiversatib in future treatment lines.

More importantly, combination of PI3K inhibitor and importin-β inhibitor effectively inhibits the growth of PIK3CA-helical-domain-mutant tumors by synchronously blocking both AKT signaling and nuclear p85β/DIRAS2 and SOWAHB axis. In this study, we evaluate the combination effect of Alpelisib and Importazole for PIK3CA helical domain mutant tumors and demonstrate its underlying mechanism.

P3, N=458, Completed, Bayer | Active, not recruiting --> Completed

We present the first comprehensive analysis of vertical inhibition of the PI3K/AKT pathway in CRC using FDA-approved drugs alpelisib and capivasertib (an AKT inhibitor) in combination with LY2584702 (an S6K inhibitor) in CRC cell lines and mouse- and patient-derived organoids (PDOs). Tissue microarrays from CRC patients confirmed that LIN28B and PI3K/AKT pathway activation correlate with CRC progression. These findings highlight the critical role of the LIN28B-mediated PI3K/AKT pathway in CRC metastasis, the therapeutic potential of targeted inhibition, and the promise of PDOs in precision medicine in metastatic CRC.

No abstract available

Human papilloma virus-negative head and neck squamous cell carcinoma (HNSCC) frequently harbors 11q13 amplifications. Copanlisib and afatinib were identified as promising candidates for combination therapy of 11q13-amplified HNSCC tumors. We demonstrated a predominant role for Ano1 in treatment resistance in Cyclin D1highAno1high HNSCC tumors and identified novel potential treatment combinations for this high-risk patient group.

P1/2, N=29, Not yet recruiting, VA Office of Research and Development | Trial completion date: Dec 2028 --> Jun 2029 | Trial primary completion date: Jun 2028 --> Dec 2028

P1, N=20, Terminated, Stemline Therapeutics, Inc. | Completed --> Terminated; The study was stopped after careful consideration of the landscape of similar drugs and evolving standard of care.