^
    3d
    Study of ERW316 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=217, Not yet recruiting, Novartis Pharmaceuticals
    New P1/2 trial • First-in-human
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
    |
    HER-2 negative
    |
    fulvestrant • letrozole
    3d
    INAVO121: A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (clinicaltrials.gov)
    P3, N=420, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Apr 2026 --> Nov 2026
    Trial primary completion date
    |
    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 negative • PIK3CA mutation
    |
    Piqray (alpelisib) • fulvestrant • Itovebi (inavolisib) • midazolam hydrochloride • omeprazole
    4d
    Efficacy and Safety of SPH4336 in Combination With Endocrine Therapy in Breast Cancer Patients With Brain Metastases. (clinicaltrials.gov)
    P2, N=52, Recruiting, Shanghai Pharmaceuticals Holding Co., Ltd | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    fulvestrant • exemestane • SPH4336
    6d
    Identification of ANT2 as a Druggable Target for Endocrine-Resistant ERα-Positive Breast Cancer. (PubMed, Int J Mol Sci)
    POH also inhibited the growth of Tamoxifen- and Fulvestrant-resistant BC cells...Finally, in silico screening using MD simulations identified venetoclax and nystatin as potential ANT2 pore binders. Both compounds reduced ERα levels in ERα-positive BC cells and increased lipid droplet formation in Fulvestrant-resistant cells. These findings highlight ANT2 as a druggable target against endocrine-resistant BC.
    Journal
    |
    ER (Estrogen receptor)
    |
    ER positive
    |
    Venclexta (venetoclax) • tamoxifen • fulvestrant
    6d
    SGLT2 Inhibitor Dapagliflozin Attenuates Cardiomyocyte Injury and Inflammation Induced by PI3Kα-Selective Inhibitor Alpelisib and Fulvestrant Under Hyperglycemia. (PubMed, Int J Mol Sci)
    Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • CCL2 (Chemokine (C-C motif) ligand 2) • IL18 (Interleukin 18) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3)
    |
    HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative
    |
    Piqray (alpelisib) • fulvestrant
    9d
    Safety and antitumour activity of ipatasertib combined with endocrine therapy and a CDK4/6 inhibitor in HR+/HER2- metastatic breast cancer (TAKTIC): a single-centre, open-label, phase 1b trial. (PubMed, Lancet Oncol)
    The combination of fulvestrant, ipatasertib, and palbociclib showed preliminary signs of clinical activity and showed expected adverse events in heavily pretreated patients with HR+/HER2- metastatic breast cancer, warranting further evaluation in those with CDK4/6 inhibitor-refractory disease.
    P1 data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • ipatasertib (RG7440) • anastrozole • exemestane
    10d
    Sapanisertib and Serabelisib (PIKTOR) in Various Combinations in Patients With HR+/HER2- Advanced/Metastatic Breast Cancer (clinicaltrials.gov)
    P1/2, N=32, Recruiting, Faeth Therapeutics
    New P1/2 trial
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    fulvestrant • sapanisertib (CB-228) • serabelisib (MLN1117)
    10d
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2, N=792, Recruiting, Hoffmann-La Roche | N=56 --> 792
    Enrollment change
    |
    PD-L1 (Programmed death ligand 1)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • letrozole • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Actemra IV (tocilizumab) • atirmociclib (PF-07220060) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    10d
    VERITAC-2: A Study to Learn About a New Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People Who Have Advanced Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=624, Active, not recruiting, Pfizer | N=219 --> 624
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    fulvestrant • Veppanu (vepdegestrant)
    10d
    TOS-358-001: A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer (clinicaltrials.gov)
    P1, N=241, Recruiting, Totus Medicines | N=175 --> 241
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • TOS-358
    10d
    OPERA-01: OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer (clinicaltrials.gov)
    P3, N=510, Recruiting, Olema Pharmaceuticals, Inc. | N=382 --> 510
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    fulvestrant • letrozole • anastrozole • exemestane • palazestrant (OP-1250)
    10d
    BREAKER-101: Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=392, Recruiting, TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=91 --> 392
    Enrollment change • First-in-human
    |
    KRAS (KRAS proto-oncogene GTPase) • 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 • HR positive + HER-2 negative
    |
    Avastin (bevacizumab) • Herceptin (trastuzumab) • 5-fluorouracil • Kisqali (ribociclib) • fulvestrant • leucovorin calcium