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    DRUG:

    LY4064809

    i
    Other names: LY4064809, STX-478, ST-814, LY-4064809, STX-H1047-PI3Kα
    Company:
    Eli Lilly
    Drug class:
    PI3Kα H1047R mutation inhibitor
    Related drugs:
    9d
    A Study of LY4064809 in Healthy Adult Chinese Participants (clinicaltrials.gov)
    P1, N=10, Recruiting, Eli Lilly and Company
    New P1 trial
    |
    LY4064809
    24d
    PIKALO-2: A Study of LY4064809 With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA) (clinicaltrials.gov)
    P3, N=920, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • letrozole • anastrozole • exemestane • LY4064809
    2ms
    PIKALO-1: First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=720, Recruiting, Eli Lilly and Company | Trial completion date: Feb 2029 --> Jul 2030 | Trial primary completion date: Feb 2027 --> Jul 2030
    Trial completion date • Trial primary completion date • First-in-human
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • letrozole • anastrozole • exemestane • LY4064809
    2ms
    A Study of Food Effect and Esomeprazole on LY4064809 in Healthy Adult Participants (clinicaltrials.gov)
    P1, N=36, Completed, Scorpion Therapeutics, a wholly owned subsidiary of Eli Lilly and Company | Recruiting --> Completed
    Trial completion
    |
    LY4064809
    3ms
    A Study of LY4064809 With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA) (clinicaltrials.gov)
    P3, N=920, Not yet recruiting, Eli Lilly and Company
    New P3 trial
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • letrozole • anastrozole • exemestane • LY4064809
    4ms
    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.
    Review • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    Piqray (alpelisib) • RLY-2608 • Itovebi (inavolisib) • LY4064809
    6ms
    STX-478-101: First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=720, Recruiting, Scorpion Therapeutics, Inc. | N=400 --> 720
    Enrollment change
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • letrozole • anastrozole • exemestane • LY4064809
    6ms
    A Study of LY4064809 [14C]-STX-478 in Healthy Male Participants (clinicaltrials.gov)
    P1, N=8, Completed, Scorpion Therapeutics, a wholly owned subsidiary of Eli Lilly and Company | Active, not recruiting --> Completed
    Trial completion
    |
    LY4064809
    7ms
    Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models. (PubMed, Br J Cancer)
    Multi-node PI3K/AKT/mTOR pathway inhibition with serabelisib, sapanisertib and ISD is highly effective in preclinical models of endometrial and breast cancer, supporting continued clinical development in these and other solid tumours.
    Preclinical • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    paclitaxel • everolimus • Piqray (alpelisib) • Truqap (capivasertib) • sapanisertib (CB-228) • RLY-2608 • Itovebi (inavolisib) • LY4064809 • serabelisib (MLN1117)
    8ms
    A Study of LY4064809 [14C]-STX-478 in Healthy Male Participants (clinicaltrials.gov)
    P1, N=8, Active, not recruiting, Scorpion Therapeutics, a wholly owned subsidiary of Eli Lilly and Company | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    LY4064809
    8ms
    A Study of LY4064809 [14C]-STX-478 in Healthy Male Participants (clinicaltrials.gov)
    P1, N=8, Recruiting, Scorpion Therapeutics, a wholly owned subsidiary of Eli Lilly and Company | Not yet recruiting --> Recruiting
    Enrollment open
    |
    LY4064809
    8ms
    A Study of LY4064809 [14C]-STX-478 in Healthy Male Participants (clinicaltrials.gov)
    P1, N=8, Not yet recruiting, Eli Lilly and Company
    New P1 trial
    |
    LY4064809