^
2d
Trial completion date
|
CD4 (CD4 Molecule)
|
sapanisertib (CB-228)
15d
New P1 trial • Metastases
|
gemcitabine • Fyarro (nanoparticle albumin-bound rapamycin)
21d
Trial completion date • Surgery
|
sapanisertib (CB-228)
29d
Phase I study of sapanisertib (CB-228/TAK-228/MLN0128) in combination with ziv-aflibercept in patients with advanced solid tumors. (PubMed, Cancer Med)
The combination of sapanisertib and ziv-aflibercept was generally tolerable and demonstrated anti-tumor activity in heavily pre-treated patients with advanced malignancies.
P1 data • Journal • Combination therapy • Metastases
|
HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
sapanisertib (CB-228) • Zaltrap (ziv-aflibercept IV)
29d
Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
P1, N=83, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Jan 2024
Trial completion • Trial completion date • Combination therapy • Surgery • Metastases
|
sapanisertib (CB-228) • Zaltrap (ziv-aflibercept IV)
1m
Dose Escalation of RMC-5552 Monotherapy in Relapsed/Refractory Solid Tumors (clinicaltrials.gov)
P1, N=108, Active, not recruiting, Revolution Medicines, Inc. | Recruiting --> Active, not recruiting
Enrollment closed
|
RMC-5552
1m
mTORC1/2 Inhibitor AZD2014 or the Oral AKT Inhibitor AZD5363 for Recurrent Endometrial and Ovarian (clinicaltrials.gov)
P1/2, N=159, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024
Trial completion date • Trial primary completion date
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • MUC16 (Mucin 16, Cell Surface Associated) • BRCA (Breast cancer early onset)
|
BRCA mutation
|
Lynparza (olaparib) • Truqap (capivasertib) • vistusertib (AZD2014)
1m
BTCRC-BRE18-337: Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers (clinicaltrials.gov)
P1/2, N=37, Active, not recruiting, Kari Wisinski | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
|
HER-2 negative • BRCA1 negative
|
Talzenna (talazoparib) • gedatolisib (PF-05212384)
1m
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
|
PIK3CA mutation
|
Ibrance (palbociclib) • gedatolisib (PF-05212384)
1m
Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025
Trial completion date • Combination therapy • Surgery • Metastases
|
sapanisertib (CB-228) • Zaltrap (ziv-aflibercept IV)
2ms
Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov)
P1, N=174, Terminated, Celgene | Active, not recruiting --> Terminated; Replaced with another clinical trial.
Trial termination
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 positive
|
Rituxan (rituximab) • avadomide (CC-122) • onatasertib (ATG-008) • spebrutinib (CC-292)
3ms
A Phase I/II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer and Incurably Poorly Differentiated or Radioidodine Refractory Differentiated Thyroid Cancer (clinicaltrials.gov)
P1/2, N=46, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Phase classification: P2 --> P1/2
Trial completion • Phase classification • Metastases
|
sapanisertib (CB-228)
3ms
Enrollment closed • Enrollment change • Combination therapy
|
everolimus
3ms
M2 Muscarinic Receptor Stimulation Induces Autophagy in Human Glioblastoma Cancer Stem Cells via mTOR Complex-1 Inhibition. (PubMed, Cancers (Basel))
N8 treatment causes autophagy via pAMPK upregulation, followed by apoptosis in both investigated cell lines. In contrast, the absence of autophagy in APE-treated GSC cells seems to indicate that cell death could be triggered by mechanisms alternative to those observed for N8.
Journal • Cancer stem
|
CASP9 (Caspase 9)
3ms
New P1/2 trial • Combination therapy • Metastases
|
gedatolisib (PF-05212384) • Nubeqa (darolutamide)
3ms
Phase I study of mTORC1/2 inhibitor sapanisertib in combination with metformin in patients with mTOR/AKT/PI3K pathway alterations and advanced solid malignancies. (PubMed, Cancer Res Commun)
The safety profile of mTORC1/2 inhibitor sapanisertib in combination with metformin was generally tolerable, with anti-tumor activity observed in patients with advanced malignancies harboring PTEN/ AKT/mTOR pathway alterations.
P1 data • Journal • Combination therapy • Metastases
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • TSC1 (TSC complex subunit 1)
|
PTEN mutation • STK11 mutation • MTOR mutation
|
sapanisertib (CB-228) • metformin
3ms
Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy • Metastases
|
letrozole • Fyarro (nanoparticle albumin-bound rapamycin)
3ms
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: Oct 2023 --> Apr 2025 | Trial primary completion date: Oct 2023 --> Apr 2025
Trial completion date • Trial primary completion date • Metastases
|
Fyarro (nanoparticle albumin-bound rapamycin)
4ms
Chronic AMPK inactivation slows SHH medulloblastoma progression by inhibiting mTORC1 signaling and depleting tumor stem cells. (PubMed, iScience)
Hk2 deletion similarly depleted medulloblastoma stem cells, implicating reduced glycolysis in the AMPK-inactivated phenotype. Our results show that AMPK inactivation disproportionately impairs medulloblastoma stem cell populations typically refractory to conventional therapies.
Journal
|
AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • PRKAA2 (Protein Kinase AMP-Activated Catalytic Subunit Alpha 2)
4ms
PRECISION 1: A phase 2, multicenter, open-label basket trial of nab-sirolimus for malignant solid tumors harboring pathogenic inactivating alterations in TSC1 and TSC2. (ASCO-GU 2024)
Collaboration with leading NGS vendors will expedite the identification of patients with qualifying TSC1 and TSC2 alterations; ongoing study access is facilitated through a just-in-time approach to trial location activation. Clinical trial information: NCT05103358.
Clinical • P2 data • Pan tumor
|
TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
Fyarro (nanoparticle albumin-bound rapamycin)
4ms
Analysis of inactivating TSC1 and TSC2 alterations in advanced genitourinary (GU) cancers from a real-world patient population in the Foundation Medicine genomic database. (ASCO-GU 2024)
Inactivating TSC1 and/or TSC2 alterations commonly occurred in GU cancers. A proportion of GU tumors have a low TMB and/or are microsatellite stable, suggesting that TSC1 and TSC2 inactivating alterations may be driver mutations rather than passenger mutations in those tumors. Therefore, patients with inactivating alterations in TSC1 or TSC2 may benefit from mTOR inhibition via nab-sirolimus.
Clinical • Real-world evidence • Tumor mutational burden • Genomic data • Real-world • Metastases
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
TP53 mutation • TMB-L • TSC1 mutation • TSC2 mutation
|
Fyarro (nanoparticle albumin-bound rapamycin)
4ms
Real-world analysis of patients with advanced gastrointestinal (GI) cancers harboring inactivating TSC1 and TSC2 alterations using the Foundation Medicine genomic database. (ASCO-GI 2024)
In exploratory biomarker analyses of patients with perivascular epithelioid cell tumors treated with the mTOR inhibitor nab-sirolimus (AMPECT, NCT02494570), those with inactivating alterations in the tumor suppressor genes TSC1 or TSC2 (critical negative regulators of mTOR activity) had confirmed responses (8/9 patients with inactivating TSC2 alterations and 1/5 patients with inactivating TSC1 alterations)...TSC1 and/or TSC2 alterations were commonly observed in GI cancers. These cancers were frequently microsatellite stable and of low TMB suggesting that these are actionable alterations that may be candidates for targeted therapy. This hypothesis is being tested in the PRECISION 1 (NCT05103358) trial which is open for enrollment or just-in-time clinical trial sites and available to patients with GI cancers harboring TSC1 or TSC2 alterations.
Clinical • Real-world evidence • Tumor mutational burden • Genomic data • Real-world • Metastases
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
TP53 mutation • KRAS mutation • TMB-L • TSC1 mutation • TSC2 mutation
|
Fyarro (nanoparticle albumin-bound rapamycin)
4ms
PRECISION 1: A phase 2, multicenter, open-label basket trial of nab-sirolimus for malignant solid tumors harboring pathogenic inactivating alterations in TSC1 and TSC2. (ASCO-GI 2024)
Collaboration with leading NGS vendors is expediting the identification of patients with qualifying TSC1 and TSC2 alterations; ongoing study access is facilitated through a just-in-time approach to trial location activation. Clinical trial information: NCT05103358.
Clinical • P2 data • Pan tumor
|
TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
Fyarro (nanoparticle albumin-bound rapamycin)
4ms
ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov)
P1, N=40, Recruiting, MEI Pharma, Inc. | Phase classification: P1b --> P1
Phase classification • Metastases
|
RAS wild-type
|
Avastin (bevacizumab) • ME-344
4ms
Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer (clinicaltrials.gov)
P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2023 --> Jun 2024 | Trial primary completion date: Aug 2023 --> Jun 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion
|
Tagrisso (osimertinib) • sapanisertib (CB-228)
4ms
A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia. (PubMed, Cancer Med)
In summary, single-agent sapanisertib had a good safety profile but limited target inhibition or efficacy in ALL as a single agent. This trial was registered at ClinicalTrials.gov as NCT02484430.
P2 data • Journal
|
EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
|
sapanisertib (CB-228)
5ms
Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov)
P1, N=174, Active, not recruiting, Celgene | Phase classification: P1b --> P1 | Trial completion date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2023 --> Jan 2024
Phase classification • Trial completion date • Trial primary completion date
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 positive
|
Rituxan (rituximab) • avadomide (CC-122) • onatasertib (ATG-008) • spebrutinib (CC-292)
5ms
Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1. (PubMed, J Clin Invest)
Bi-steric inhibitors had strong growth inhibition, eliminated phosphorylated 4EBP1, and induced more apoptosis than rapamycin or MLN0128. De novo purine synthesis was selectively inhibited by bi-sterics through reduction in JUN and its downstream target PRPS1 and appeared to be the cause of apoptosis. Hence, bi-steric mTORC1-selective inhibitors are a therapeutic strategy to treat tumors driven by mTORC1 hyperactivation.
Preclinical • Journal
|
EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • PRPS1 (Phosphoribosyl Pyrophosphate Synthetase 1)
|
sapanisertib (CB-228) • sirolimus
5ms
A Phase 3 study of gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/ HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor plus a non-steroidal aromatase inhibitor (VIKTORIA-1) (SABCS 2023)
Those with PIK3CA mutations will be assigned to Study 2 (n=350) and randomized to Arm D (geda, P, and F), Arm E (alpelisib and F), or Arm F (geda and F). Enrollment is ongoing. This trial abstract was previously presented at the 2022 San Antonio Breast Cancer Symposium, December 6-10, 2022.
Clinical • P3 data • Metastases
|
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) • Piqray (alpelisib) • fulvestrant • gedatolisib (PF-05212384)
5ms
Phase 2 Trial with Safety Run-In of Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast CancersBig Ten Cancer Research Consortium BTCRC-BRE18-337 (SABCS 2023)
Although this study did not meet its primary endpoint, there were 2 TNBC patients without a gBRCA1/2 mutation who achieved a partial response to this non-chemotherapy regimen. Future biomarker testing may help elucidate these findings and possible predictors of response.
Clinical • P2 data • BRCA Biomarker • PARP Biomarker • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
|
BRCA2 mutation • BRCA1 mutation • HER-2 negative • PIK3CA mutation • BRCA mutation • BRCA1 positive • BRCA1 negative • BRCA2 positive
|
Talzenna (talazoparib) • gedatolisib (PF-05212384)
5ms
Enrollment open • Combination therapy • Metastases
|
letrozole • Fyarro (nanoparticle albumin-bound rapamycin)
5ms
A PHASE 2, OPEN-LABEL, SINGLE-ARM, PROSPECTIVE, MULTICENTER STUDY OF NAB-SIROLIMUS PLUS LETROZOLE IN ADVANCED OR RECURRENT ENDOMETRIOID ENDOMETRIAL CANCER (IGCS 2023)
The relationship between biomarkers and response outcomes is an exploratory endpoint. Current Trial Status: Open for enrollment.
Clinical • P2 data • IO biomarker • Metastases
|
ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog)
|
letrozole • Fyarro (nanoparticle albumin-bound rapamycin)
5ms
PHASE 2, MULTICENTER, GLOBAL, OPEN-LABEL BASKET TRIAL OF NAB-SIROLIMUS FOR PATIENTS WITH INACTIVATING ALTERATIONS IN TSC1 AND TSC2 (PRECISION I) (IGCS 2023)
Current Trial Status: Enrollment began in March 2022 and is expedited through collaboration with leading NGS providers. Patients with urothelial, endometrial, ovarian, and cervical cancers are expected to be enrolled based on the frequency of TSC1 and TSC2 inactivating alterations (Figure).
Clinical • P2 data • Pan tumor
|
TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
Fyarro (nanoparticle albumin-bound rapamycin)
5ms
RMC-5552 Monotherapy in Adult Subjects With Recurrent Glioblastoma (clinicaltrials.gov)
P1, N=48, Active, not recruiting, Nicholas Butowski | Recruiting --> Active, not recruiting
Enrollment closed
|
CASP3 (Caspase 3) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • AKT1S1 (AKT1 Substrate 1)
|
RMC-5552
6ms
Trial completion date • Combination therapy
|
AFP (Alpha-fetoprotein)
|
temozolomide • irinotecan • Fyarro (nanoparticle albumin-bound rapamycin)
6ms
Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer (clinicaltrials.gov)
P1; Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date • Metastases
|
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)
6ms
Clinical • P2 data • Late-breaking abstract • Pan tumor
|
TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
Fyarro (nanoparticle albumin-bound rapamycin)
7ms
Cytochrome b561 regulates iron metabolism by activating the Akt/mTOR pathway to promote Breast Cancer Cells proliferation. (PubMed, Exp Cell Res)
Importantly, the dual mTOR inhibitor MLN0128 (50 nM, 48 h) down-regulated CYB561 expression and the iron metabolism-related proteins transferrin receptor, divalent metal transporter 1, and ferritin heavy chain 1, whereas the mTOR agonist MHY1485 rescued the down-regulation of CYB561 knockdown on iron metabolism-related proteins. We conclude that CYB561 promotes the proliferation of BC cells by regulating iron metabolism through the activation of the Akt/mTOR signaling pathway.
Journal
|
CYB5A (Cytochrome B5 Type A)
|
sapanisertib (CB-228)
7ms
Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. (PubMed, Chem Biol Interact)
Our study reveals that CTR1 contributes to pancreatic tumorigenesis and progression, by up-regulating the phosphorylation of AKT/mTOR signaling molecules. Recovering copper balance by copper deprivation addresses as promising strategy for improved cancer chemotherapy.
Journal
|
sirolimus
8ms
Clinical • P2 data • Pan tumor
|
TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
|
TSC1 mutation • TSC2 mutation
|
Fyarro (nanoparticle albumin-bound rapamycin)