Piqray (alpelisib) / Novartis - LARVOL DELTA

Tipifarnib (TIP) and alpelisib (ALP) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 1 results from KURRENT-HN (ESMO 2025) - No abstract available

Metastases • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Alpelisib (ALP) + fulvestrant (FUL) therapy in patients (pts) with PIK3CA-mutated (mut) HR+, HER2− advanced breast cancer (ABC) who progressed on/after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + aromatase inhibitor (AI): Primary analysis (PA) of EPIK-B5 study [WITHDRAWN] (ESMO 2025) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer. (PubMed, Mol Diagn Ther) - "Inhibitors of kinase PI3K have been in clinical development for several years but only two drugs, the alpha catalytic sub-unit specific inhibitor alpelisib and more recently inavolisib, also an inhibitor of the alpha catalytic sub-unit, have been approved for a cancer indication, in metastatic breast cancer. Other factors, such as the specific type of PIK3CA mutations arising in the catalytic domain, the helical domain, or other areas of the gene, which may affect the mutation functional repercussions and the inhibitor effectiveness, have not been fully taken into consideration. This review details the progress of PI3K inhibitors' development in colorectal cancer, addresses hurdles in development, and proposes areas for potential advancement."

Journal • Review • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • PIK3CA

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Precision Treatment of Recurrent/Metastatic Salivary Gland Carcinoma Guided by Molecular Typing (clinicaltrials.gov) - P2 | N=39 | Recruiting | Sponsor: Peking Union Medical College | N=10 ➔ 39 | Trial completion date: Jul 2026 ➔ Jul 2028

Enrollment change • Trial completion date • Oncology • Salivary Gland Cancer

SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast) (clinicaltrials.gov) - P2 | N=130 | Active, not recruiting | Sponsor: Borstkanker Onderzoek Groep | Trial primary completion date: Dec 2024 ➔ Jan 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial primary completion date • Breast Cancer • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR • PIK3CA

Radiation Recall Dermatitis Following Capivasertib Administration. (PubMed, Pract Radiat Oncol) - "Capivasertib is a small-molecule inhibitor targeting the phosphatidylinositol 3-kinase/protein kinase B pathway recently approved in locally advanced and metastatic breast cancer; however, the safety of its use in the setting of palliative radiation is currently unclear. Here, we report a case of radiation recall dermatitis in a patient with metastatic breast cancer on capivasertib with history of radiation to the right lower extremity managed with corticosteroids, antibiotics, and switching to alpelisib."

Journal • Breast Cancer • Dermatitis • Dermatology • Immunology • Oncology • Solid Tumor

Complete Response With Alpelisib and Trastuzumab in a Patient With Estrogen Receptor-/Progesterone Receptor-Negative, Human Epidermal Growth Factor Receptor 2-Positive Refractory Metastatic Breast Cancer. (PubMed, JCO Precis Oncol) - No abstract available

Journal • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Structural Insights into the Development of Inhibitors Against Cancer-Specific Mutations of PI3Kα. (PubMed, Annu Rev Pharmacol Toxicol) - "While early pan- and isoform-selective PI3K inhibitors (alpelisib) show clinical utility, their intrinsic toxicity and resistance to treatment persist. Recent breakthroughs include the emergence of allosteric inhibitors (RLY-2608 and STX-478) that exploit mutation-induced cryptic pockets to achieve mutant selectivity as well as covalent inhibitors and degraders (inavolisib) that enhance specificity, aiming at decoupling antitumor activity from metabolic dysfunction. This review synthesizes current progress in PI3Kα inhibitor development, emphasizing structural characteristics, clinical challenges, and emerging strategies. Addressing challenges to increase mutant selectivity, exploring conformational modulation, uncovering new mechanisms of action, and implementing personalized therapies are key future directions for PI3Kα-targeted drug discovery."

Journal • Review • Metabolic Disorders • Oncology • PIK3CA

Mechanistic modeling of cell viability assays with in silico lineage tracing. (PubMed, PLoS Comput Biol) - "Using our previously developed model of mammalian single-cell proliferation and death signaling, we simulated drug dose response experiments for four targeted anti-cancer drugs (alpelisib, neratinib, trametinib and palbociclib) and compared them to experimental data. Variations in mother cells prior to drug treatment impinging on ERK pathway activity are associated with the rapidly dividing phenotype and trametinib resistance. This work lays a foundation for the application of mechanistic modeling to large-scale cell viability datasets and better understanding determinants of cellular heterogeneity in drug response."

Journal • Oncology

Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors reduce vascular inflammation in vitro and in vivo. (PubMed, Br J Pharmacol) - "Selective p110α inhibition of vascular inflammation may provide a novel therapeutic pathway for limiting adverse tissue swelling. Moreover, the limited effect of BYL-719 on C5a-mediated responses implies that this innate component of the immune response will continue to provide essential defence activity during p110α blockade."

Journal • Preclinical • Dermatitis • Inflammation • IL1B • PIK3CA • TNFA

Trastuzumab + Alpelisib +/- Fulvestrant vs Trastuzumab + CT in Patients With PIK3CA Mutated Previously Treated HER2+ Advanced BrEasT Cancer (ALPHABET) (clinicaltrials.gov) - P3 | N=27 | Active, not recruiting | Sponsor: Spanish Breast Cancer Research Group | Trial primary completion date: Jun 2025 ➔ Jun 2026 | Trial completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR • PIK3CA

EPIK-O: Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected (clinicaltrials.gov) - P3 | N=358 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2025 ➔ Dec 2025

Platinum resistant • Trial completion date • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA

ALPINIST: Study to Assess the Safety of Alpelisib Plus Fulvestrant, in Men and Post-menopausal Women With HR-positive, HER2-negative, Advanced Breast Cancer (aBC) With PIK3CA Mutation, Whose Disease Progressed on or After Endocrine Treatment (clinicaltrials.gov) - P4 | N=40 | Completed | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Completed | N=100 ➔ 40 | Trial completion date: Nov 2025 ➔ Jun 2025 | Trial primary completion date: Nov 2025 ➔ Jun 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

KURRENT-HN: Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (clinicaltrials.gov) - P1/2 | N=40 | Active, not recruiting | Sponsor: Kura Oncology, Inc. | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jul 2025 ➔ Dec 2025

Biomarker • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS • PIK3CA

OP-1250-003: Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, or Everolimus in ER+, HER2- Breast Cancer (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Integrating Bulk RNA and Single-cell transcriptome to explore the role of glycan-related genes in lung adenocarcinoma. (PubMed, J Cancer) - "Furthermore, based on the molecular characteristics, we identified several potential candidate drugs for personalized treatment, including docetaxel, alpelisib, and gefitinib. Our study found that glycan-related genes could alter the composition of immune cell infiltration in LUAD tumor tissues and might affect the interaction between immune cells and tumor cells through intercellular section signals, resulting in the inability of immune cells to normally initiate immune responses against tumor cells. These findings offer new biological perspectives of glycan-related genes in shaping the TME and potential targets for personalized LUAD treatment."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

EPIK-B5: Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor. (clinicaltrials.gov) - P3 | N=212 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2028 ➔ Oct 2026 | Trial primary completion date: Jan 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

CCDC138 overexpression predicts poor prognosis and highlights ciliopathy-linked mechanisms in uterine corpus endometrial carcinoma. (PubMed, Front Mol Biosci) - "Drug sensitivity analysis showed increased responsiveness to chemotherapeutic agents like 5-fluorouracil and alpelisib in high-CCDC138 tumors. These findings underscore CCDC138's role in UCEC progression, immune modulation, and therapeutic responsiveness, highlighting its potential as a prognostic biomarker and therapeutic target. Its shared relevance in UCEC and ciliopathies suggests broader implications for targeted therapies."

Journal • Endometrial Cancer • Gynecologic Cancers • Immune Modulation • Immunology • Oncology • Solid Tumor • Uterine Cancer • CDKN1A • CEP72 • mTOR • MYCN

SAFIR 03: Detection of Tumor DNA in the Blood of Patients Receiving Standard Therapy for Hormone Receptor-positive (HR+) Non-HER2 Expressing (HER2-) Metastatic Breast Cancer as a Tool to Select Those Who May Benefit From the Next Course of Fulvestrant in Combination With Alpelisib or Ribociclib (clinicaltrials.gov) - P2 | N=162 | Active, not recruiting | Sponsor: UNICANCER | Recruiting ➔ Active, not recruiting

Circulating tumor DNA • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR • PIK3CA

Craniofacial vascular malformation with PIK3CA activating mutation in a 15-year-old patient (ECP 2025) - "This mutation has been reported in vascular malformations and is druggable with AKT (miransertib) and PI3K (alpelisib) inhibitors. This case underscores the role of PIK3CA mutations in vascular malformations and their potential therapeutic relevance. Molecular profiling in vascular anomalies can guide therapeutic decisions, offering new treatment avenues for patients with refractory or symptomatic lesions. Further research is needed to establish standardized molecular-driven treatment strategies for these conditions."

Clinical • CALD • PDPN • PIK3CA

Personalising outcomes with patient-derived tumour organoid (PDTO) anal squamous cell carcinoma (ASCC) models (ESCP 2025) - "Molecular directed therapies with alpelisib (PI3-kinase inhibitor) or abemaciclib (CDK4/6 inhibitor) demonstrated efficacy against PDTOs with PIK3CA mutation or p16 loss, respectively...Co-culture studies with HER2 CAR-T cells demonstrated cytotoxicity against HER2 positive organoids, which was enhanced by anti-PD-1 blockade. Conclusion This world first PDTO biobank is an invaluable translational platform for disease modelling and can be utilised in future co clinical trials to interrogate vulnerabilities in relapsed ASCC."

Clinical • IO biomarker • Anal Carcinoma • Oncology • Squamous Cell Carcinoma • EP300 • HER-2 • KMT2D • MUC4 • PIK3CA • SOX2 • TP53 • TP63

Activation of PI3K and deletion of p53 in keratin 15-expressing mouse mammary cells induces tumor heterogeneity and plasticity modeling metaplastic breast cancer. (PubMed, J Pathol) - "These Pik3ca-activated tumor cells were more sensitive to alpelisib, a p110α-selective inhibitor approved by the FDA for the treatment of some PIK3CA mutant cancers, compared to Pik3ca WT cells.."

Heterogeneity • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • AR • PI3K • PIK3CA • TP53

EPIK-B6: Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2027 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Treatment of Ovarian Clear Cell Carcinoma: A Case of Successful Management With Targeted Therapies. (PubMed, Case Rep Obstet Gynecol) - "Case: A 56-year-old woman was diagnosed with ovarian clear cell carcinoma and treated with surgical management as well as carboplatin and paclitaxel...A durable response was achieved first with alpelisib, chosen based on genomic testing. When progression occurred on this agent, a partial disease response was achieved with the combination of nivolumab and ipilimumab. The use of targeted therapies as well as the combination of nivolumab and ipilimumab is a promising option in advanced and recurrent cases of ovarian clear cell carcinoma."

Journal • Clear Cell Carcinoma • Oncology • Ovarian Cancer • Solid Tumor