^
    4d
    SARC046: A Phase II Trial of Nab-Sirolimus in Patients With Progressing or Symptomatic Epithelioid Hemangioendothelioma (clinicaltrials.gov)
    P2, N=41, Recruiting, Sarcoma Alliance for Research through Collaboration | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Fyarro (nanoparticle albumin-bound rapamycin)
    10d
    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=18, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open
    |
    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
    |
    gemcitabine • Fyarro (nanoparticle albumin-bound rapamycin)
    12d
    Coexistent PTEN and PIK3CA alterations hyperactivate mTORC1 signaling in endometrial cancers and cause their selective sensitivity to mTORC1 inhibition. (PubMed, bioRxiv)
    These findings are consistent with a phase I trial of bi-steric mTORC1 inhibitor RMC-5552, showing anti-tumor activity in patients with EC. PDXs with KRAS co-mutations regrew after RMC-6272 treatment, which was prevented by the addition of the RAS(ON) multi-selective inhibitor RMC-7977...Single mutant tumors are sensitive to PI3K inhibition but those with both mutations are insensitive to PI3K or AKT inhibition but are exquisitely dependent on mTORC1 kinase. This provides strong preclinical rationale for targeting mTORC1, alone or combined with RAS inhibition (in RAS co-mutant tumors), as an effective therapeutic strategy.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    KRAS mutation • PIK3CA mutation • RAS mutation
    |
    RMC-7977 • RMC-5552
    1m
    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=18, Active, not recruiting, M.D. Anderson Cancer Center | N=12 --> 18
    Enrollment change
    |
    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
    |
    gemcitabine • Fyarro (nanoparticle albumin-bound rapamycin)
    2ms
    mTORC1/2 Inhibitor AZD2014 or the Oral AKT Inhibitor AZD5363 for Recurrent Endometrial and Ovarian (clinicaltrials.gov)
    P1, N=159, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    BRCA mutation
    |
    Lynparza (olaparib) • Truqap (capivasertib) • vistusertib (AZD2014)
    3ms
    Combining brigatinib with mTOR inhibition to effectively treat NF2-SWN-associated and sporadic NF2-deficient meningiomas. (PubMed, Cancer Res Commun)
    We previously generated an orthotopic, NF2-deficient meningioma model using the luciferase-expressing Ben-Men-1 cell line established from a sporadic tumor and identified the multi-kinase inhibitor brigatinib and the mTOR kinase inhibitor INK128 to potently impede tumor growth. As the first NF2-SWN-related meningioma cell line, AG-NF2-Men is a unique reagent for investigating meningioma biology and therapeutics. A clinical trial to evaluate the combination of brigatinib with an mTOR inhibitor in NF2-deficient meningiomas is warranted.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NF2 (Neurofibromin 2)
    |
    Alunbrig (brigatinib) • sapanisertib (CB-228)
    3ms
    EVERLAST: Everolimus Aging Study (clinicaltrials.gov)
    P2, N=106, Active, not recruiting, University of Wisconsin, Madison | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Sep 2026 | Trial primary completion date: Dec 2025 --> Sep 2026
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    everolimus
    3ms
    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
    |
    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
    |
    sapanisertib (CB-228)
    3ms
    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)
    4ms
    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)
    |
    NPM1 mutation
    |
    Venclexta (venetoclax) • sapanisertib (CB-228)
    4ms
    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)
    4ms
    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)