Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.

In HR+/HER2-/PIK3CA-mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia. Novartis Pharmaceuticals.

Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

P3, N=27, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=300 --> 27 | Trial completion date: Sep 2026 --> Nov 2024 | Trial primary completion date: Jun 2026 --> Nov 2024

P1, N=32, Recruiting, Columbia University

P2, N=70, Active, not recruiting, National Cancer Institute (NCI)

Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

Anaplastic thyroid cancer (ATC), a rare and aggressive malignancy with a poor prognosis, has shown promise with the approved dabrafenib/trametinib combination for BRAFV600E mutation. The combination of trametinib and alpelisib showed promise as a strategy for treating ATC with co-mutations in BRAF and PI3KCA, both in vitro and in vivo. This combination offers insights into overcoming resistance to BRAF-targeted treatments in ATC with mutations in BRAF and PI3KCA.

P1/2, N=13, Active, not recruiting, Brown University | Trial completion date: May 2024 --> Jan 2027 | Trial primary completion date: Jan 2024 --> Jan 2027

Approvals for oestrogen receptor-positive advanced breast cancer include the PI3K inhibitor alpelisib for PIK3CA-mutated tumours, the AKT inhibitor capivasertib for tumours with alterations in PIK3CA, AKT1, or PTEN, and the mTOR inhibitor everolimus, which is used irrespective of mutation status. The availability of different inhibitors leaves physicians with a potentially challenging decision over which of these therapies should be used for individual patients and when. In this Review, we present a comprehensive summary of our current understanding of the pathways and the three inhibitors and discuss strategies for the optimal sequencing of therapies in the clinic, particularly after progression on a CDK4/6 inhibitor.

P1, N=256, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting

P1/2, N=29, Not yet recruiting, VA Office of Research and Development | Phase classification: P2 --> P1/2 | Trial completion date: Jun 2028 --> Dec 2028 | Trial primary completion date: Dec 2027 --> Jun 2028

By investigating the Genomics of Drug Sensitivity in Cancer (GDSC) database, we identified axitinib and taselisib as candidate compounds that could potentially target the KISS-high myeloblasts. Altogether, our findings suggest that KISS holds the potential to improve the current prognostic scheme of MDS and inform novel therapeutic opportunities.

Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.

P1, N=24, Terminated, Haihe Biopharma Co., Ltd. | N=350 --> 24 | Recruiting --> Terminated; Business decision

P4, N=100, Recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Furthermore, differences in AEs emerged between patients with PIK3CA-mutated breast cancer and those with PROS. This study provides vital insights for healthcare professionals to navigate AEs in clinical practice and informs future research for enhancing alpelisib 's safety profile.

Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.

P=N/A, N=60, Recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Jun 2024 | Trial primary completion date: Dec 2024 --> Jun 2024

P2, N=69, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=135 --> 69

P1/2; N=204 --> 24 | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Jun 2023

P1/2; Phase classification: P2 --> P1/2

P1/2, N=306, Recruiting, Risen (Suzhou) Pharma Tech Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=98, Active, not recruiting, Ludwig-Maximilians - University of Munich | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2022 --> Sep 2023

A risk model using 5 clinically relevant baseline characteristics was able to identify patients at higher or lower probability for developing alpelisib-induced hyperglycemia. Early identification of patients who may be at higher risk for hyperglycemia may improve management (including monitoring and early intervention) and potentially lead to improved outcomes.

However, following the breast cancer-specific FDA approvals of alpelisib+fulvestrant for PIK3CA-mutant disease in 2019 and elacestrant for ESR1-mutant disease in 2023, a significant shift in Level 1 actionability was observed between EUR (45%) and AFR (34%) attributed in part to the paucity of PIK3CA (26.3% vs. 36.2% in EUR) and ESR1 (4.1% vs. 7.5% in EUR) oncogenic alterations in AFR.We further observed AFR with CRC to have lower prevalence of MSI-H (5.8% vs.10.7% in EUR), TMB (12.5% vs. 18.8% in EUR) and BRAF V600E (5.1% vs. 9% in EUR). Correspondingly, in 2023, 16.4% of AFR with CRC have Level 1 alterations compared to 25.4% of EUR. Moreover, while AFR have higher rates of KRAS mutations (57.2% vs. 42.6% in EUR), they have a lower prevalence of the standard care biomarker KRAS G12C (3.4% vs. 7% of KRAS-mutant CRC in EUR) further exacerbating the disparities in CRC clinical actionability.Taken together, here we demonstrate that a significant disparity exists in the clinical actionability landscape of AFR with cancer compared to EUR, largely due to differences in relative mutational frequencies of Level 1 genomic alterations.

P3, N=234, Recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2025

P3, N=20, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2024 --> Sep 2024 | Trial primary completion date: Apr 2024 --> Sep 2024

P1, N=68, Active, not recruiting, Otto Metzger, MD | Trial completion date: Dec 2023 --> May 2024

P2, N=15, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=106 --> 15

P1, N=8, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2023

A radiosensitizing effect can be confirmed after treatment with AZD0156, Afatinib or Alpelisib in three organoid lines using this assay so far. Establishment of HNSCC organoids was successful using our workflow. These 3D models can be used to screen for potential radiosensitizers. For validation, we established an organoid formation assay to determine the clonogenic survival as an important endpoint in radiobiology.

P2, N=51, Recruiting, GOG Foundation | Not yet recruiting --> Recruiting

We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide...Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner...Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in high-grade tumors.

P1, N=265, Active, not recruiting, Relay Therapeutics, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jul 2024 | Trial primary completion date: Dec 2025 --> Jun 2024

Binding affinities predicted via thermodynamic integration (TI) are in good agreement with previously reported IC50s. Yet, computationally demanding techniques such as TI might not always be the most efficient approach for affinity prediction, as in our case study, fast high-throughput techniques were capable of classifying compounds as active or inactive, and one docking approach showed accuracy comparable to TI.

P3, N=358, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=50, Not yet recruiting, Murdoch Childrens Research Institute | N=30 --> 50 | Trial completion date: Sep 2028 --> Nov 2026 | Initiation date: Sep 2023 --> Apr 2024 | Trial primary completion date: Sep 2026 --> Jun 2026

P3, N=325, Active, not recruiting, Hoffmann-La Roche | Phase classification: P2/3 --> P3

P=N/A, N=0, No Longer Available, Bayer