^
    16h
    A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer (clinicaltrials.gov)
    P2, N=80, Recruiting, Hoffmann-La Roche | N=44 --> 80 | Trial completion date: Dec 2030 --> Feb 2030
    Enrollment change • Trial completion date • Trial initiation date
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    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
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    ER positive • PIK3CA mutation
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    Kisqali (ribociclib) • fulvestrant • Itovebi (inavolisib)
    5d
    Targeted Therapies in Infantile Hemangiomas and Vascular Malformations: From β-Blockers to PI3K/AKT/mTOR Inhibitors. (PubMed, J Cell Mol Med)
    The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.
    Review • Journal
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    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    Piqray (alpelisib) • sirolimus
    5d
    Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer (clinicaltrials.gov)
    P2, N=69, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Jan 2027 | Trial primary completion date: Mar 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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    HER-2 negative • PIK3CA mutation
    |
    Piqray (alpelisib) • fulvestrant
    6d
    Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial. (PubMed, Breast Cancer Res Treat)
    This prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • EGFR positive • HR positive + HER-2 negative
    |
    Piqray (alpelisib) • fulvestrant
    6d
    EPIK-L1: Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. (clinicaltrials.gov)
    P2/3, N=232, Recruiting, Novartis Pharmaceuticals | N=158 --> 232
    Enrollment change
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    Piqray (alpelisib)
    6d
    A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer (clinicaltrials.gov)
    P2, N=38, Recruiting, Hoffmann-La Roche | N=14 --> 38
    Enrollment change
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
    |
    ER positive • PIK3CA mutation
    |
    Kisqali (ribociclib) • fulvestrant • Itovebi (inavolisib)
    7d
    A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer (clinicaltrials.gov)
    P2, N=60, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting
    Enrollment open • Trial initiation date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    ER positive • HER-2 negative • PIK3CA mutation • HER-2 negative + ER positive
    |
    Kisqali (ribociclib) • letrozole • Itovebi (inavolisib)
    7d
    INAVO122: A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=230, Recruiting, Hoffmann-La Roche | Trial primary completion date: Sep 2026 --> Dec 2026
    Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • PIK3CA mutation
    |
    tamoxifen • fulvestrant • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    11d
    EPIK-B3: Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss (clinicaltrials.gov)
    P3, N=137, Terminated, Novartis Pharmaceuticals | Trial completion date: Jan 2027 --> Feb 2026 | Active, not recruiting --> Terminated; The study was terminated following a strategic decision to halt recruitment due to persistently slow enrollment. This decision was not driven by any new or unexpected safety concerns.
    Trial completion date • Trial termination
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation
    |
    Piqray (alpelisib) • albumin-bound paclitaxel
    13d
    CO46274: A Phase II Study Evaluating the Efficacy and Safety of Inavolisib plus Ribociclib plus Fulvestrant Versus Placebo plus Ribociclib plus Fulvestrant in Patients with Advanced Breast Cancer (2025-523013-28-00)
    P1/2, N=14, Not yet recruiting, F. Hoffmann-La Roche AG
    New P1/2 trial
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
    |
    ER positive • PIK3CA mutation
    |
    Kisqali (ribociclib) • fulvestrant • Itovebi (inavolisib)
    19d
    Model-Based Patient Selection and Dosing Strategies for HRAS and PIK3CA Dysregulated HNSCC: A QSP Model for Alpelisib and Tipifarnib Combination. (PubMed, Clin Pharmacol Ther)
    Global sensitivity analysis identified compensatory feedback, tumor proliferation rate, and PI3K-mTOR crosstalk as key determinants of tumor response. This novel QSP application exemplifies an innovative bottom-up modeling approach to support patient selection and dosing strategies for future clinical studies.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RHEB (Ras Homolog, MTORC1 Binding)
    |
    PIK3CA mutation
    |
    Piqray (alpelisib) • Zarnestra (tipifarnib)
    20d
    A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    ER positive • HER-2 negative • PIK3CA mutation • HER-2 negative + ER positive
    |
    Kisqali (ribociclib) • letrozole • Itovebi (inavolisib)