^
    4d
    Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations (clinicaltrials.gov)
    P2, N=17, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Nov 2026
    Trial completion date
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    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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    sapanisertib (CB-228)
    10d
    Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | N=85 --> 22 | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • BRAF V600K • KEAP1 mutation • NFE2L2 mutation
    |
    Guardant360® CDx • MSK-IMPACT
    |
    sapanisertib (CB-228) • telaglenastat (CB-839)
    17d
    Genomic and transcriptomic characterization of acute myeloid leukaemia with IL3RA overexpression: Prognostic and therapeutic implications revisited. (PubMed, Br J Haematol)
    Pharmaco-transcriptomic analysis revealed that IL3RA-high AML exhibited selective sensitivity to venetoclax and sapanisertib, suggesting potential synergistic opportunities. In conclusion, IL3RA overexpression defines a clinically and biologically distinct subgroup of AML, with unique therapeutic vulnerabilities. Continued research efforts are warranted to integrate CD123-directed therapies into the upfront AML treatment paradigm.
    Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • CD123 (Interleukin 3 Receptor Subunit Alpha) • NUP214 (Nucleoporin 214) • FUS (FUS RNA Binding Protein) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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    NPM1 mutation
    |
    Venclexta (venetoclax) • sapanisertib (CB-228)
    21d
    A Phase I Trial of Combination Gemcitabine and Nab-Sirolimus in Advanced Leiomyosarcomas or Advanced Soft-Tissue Sarcomas With TSC2 or TSC1 Loss-of-function Mutations or Deletions (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    gemcitabine • Fyarro (nanoparticle albumin-bound rapamycin)
    22d
    Dose-escalation Study to Assess Safety and Pharmacokinetics of Nab-Sirolimus in Patients With Locally Advanced or Metastatic Solid Tumors and Moderate Liver Impairment (clinicaltrials.gov)
    P1, N=28, Recruiting, Aadi Bioscience, Inc. | Trial completion date: Apr 2025 --> Aug 2026 | Trial primary completion date: Apr 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    Fyarro (nanoparticle albumin-bound rapamycin)
    22d
    EEC-201: Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer (clinicaltrials.gov)
    P2, N=29, Recruiting, Aadi Bioscience, Inc. | Trial completion date: Oct 2026 --> Jun 2027 | Trial primary completion date: Mar 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    letrozole • Fyarro (nanoparticle albumin-bound rapamycin)
    2ms
    The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial. (PubMed, Clin Cancer Res)
    The success of TM-mediated prophylaxis and the clearance of selected variants in ctDNA are concordant with selective, on-mechanism, antitumor activity following RMC-5552 treatment. These data show that RMC-5552, the first bi-steric mTORC1-selective inhibitor in the clinic, is active at tolerable doses, and that selective inhibition of mTORC1 alleviates mTORC2-mediated hyperglycemia, overcoming a key limitation of prior mTOR inhibitors.
    P1 data • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    RMC-5552
    3ms
    RMC-5552 Monotherapy in Adult Subjects With Recurrent Glioblastoma (clinicaltrials.gov)
    P1, N=48, Recruiting, Nicholas Butowski | Suspended --> Recruiting
    Enrollment open
    |
    EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    RMC-5552
    3ms
    Extracellular Matrix and Fibroblast Activation in Lymphangioleiomyomatosis. (PubMed, Am J Respir Cell Mol Biol)
    This demonstrates that mTORC1-driven 4E-BP1/eIF4E rapamycin-insensitive translational control overrides transcriptional control of ECM genes. Inhibition by RMC-5552 of ECM and fibroblast activation may result in destruction of CSC-like LAM cells and provide more enduring therapy for LAM patients.
    Journal
    |
    EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • TGFB1 (Transforming Growth Factor Beta 1) • COL1A1 (Collagen Type I Alpha 1 Chain) • COL6A1 (Collagen Type VI Alpha 1 Chain)
    |
    RMC-5552
    3ms
    Identification of anoikis-related genes to develop a risk model and predict the prognosis and tumor microenvironment in rectal adenocarcinoma. (PubMed, Front Genet)
    Drug sensitivity analysis revealed differences in the IC50 values of OSI-027, PLX-4720, UMI-77, and Sapitinib between the high-risk and low-risk groups. Enrichment analysis revealed that these prognostic ARGs were primarily enriched in pathways and biological processes related to tumorigenesis. The risk model of ARGs can effectively predict READ prognosis and provide potential therapeutic targets.
    Journal
    |
    BRCA1 (Breast cancer 1, early onset) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • KRT17 (Keratin 17)
    |
    PLX4720 • AVTX-006 • sapitinib (AZD8931)
    3ms
    RMC-5552 Monotherapy in Adult Subjects With Recurrent Glioblastoma (clinicaltrials.gov)
    P1, N=48, Suspended, Nicholas Butowski | Trial completion date: Dec 2025 --> Apr 2030 | Trial primary completion date: Dec 2025 --> Apr 2030
    Trial completion date • Trial primary completion date
    |
    EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    RMC-5552
    4ms
    WZ4003 sensitizes hepatocellular carcinoma to OSI-027 by inhibiting ARK5-mediated autophagy. (PubMed, Cancer Lett)
    Notably, both chloroquine treatment and ULK1-S757E transfection abolished the OSI-027/WZ4003 synergy. Moreover, elevated ARK5 expression was observed in HCC specimens and was independently associated with an unfavorable recurrence-free survival (RFS). Our findings propose a novel strategy for augmenting sensitivity to OSI-027 in HCC, further underscoring the significance of ARK5 and autophagy as cancer therapeutic targets.
    Journal
    |
    NUAK1 (NUAK Family Kinase 1)
    |
    AVTX-006