- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Unconventional mechanism of action and resistance to rapalogs in renal cancer. (Pubmed Central) - Jun 11, 2024
Thus, enforced mTORC1 activation in the TME is sufficient to confer resistance to rapalogs. These studies highlight the importance of mTORC1 inhibition in nontumor cells for rapalog antitumor activity and provide an explanation for the lack of mTOR resistance mutations in RCC patients.
- |||||||||| Avastin (bevacizumab) / Roche, Torisel (temsirolimus) / Pfizer
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer (clinicaltrials.gov) - May 20, 2024
P1, N=278, Active, not recruiting,
These results have important implications for immune responses during clinical treatments and in disease states where mTOR is suppressed. Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026
- |||||||||| Review, Journal: Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas. (Pubmed Central) - Apr 28, 2024
Other combination therapies include pembrolizumab (targeting programed cell death protein 1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Torisel (temsirolimus) / Pfizer
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease (clinicaltrials.gov) - Apr 25, 2024
P1, N=155, Active, not recruiting,
Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors. Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2026
- |||||||||| Fyarro (nanoparticle albumin-bound rapamycin) / Aadi Biosci, Torisel (temsirolimus) / Pfizer
Antitumor activity of nab-sirolimus versus mTOR inhibitors temsirolimus, sirolimus, and everolimus in A549 NSCLC xenografts. () - Apr 24, 2024 - Abstract #ASCO2024ASCO_4757;
nab-Sirolimus resulted in significantly higher intratumoral drug concentration, stronger inhibition of mTOR targets, and greater antitumor activity compared to other IV and oral mTORis in a KRAS/STK11/KEAP1 mutated NSCLC xenograft model. These results support further clinical evaluation of nab-sirolimus as a single agent or in combination with other therapeutic agents in oncology.
- |||||||||| Trial completion date, Metastases: Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer (clinicaltrials.gov) - Apr 4, 2024
P2, N=349, Active, not recruiting,
- |||||||||| everolimus / Generic mfg.
Journal: Chemical Proteomics Reveals that the Anticancer Drug Everolimus Affects the Ubiquitin-Proteasome System. (Pubmed Central) - Mar 14, 2024
Moreover, the everolimus treatment resulted in both ubiquitin phosphorylation and generation of a significant amount of semitryptic peptides, illustrating the increase in the protease activity. These observations suggest that everolimus affects the UPS in a unique way, and its mechanism of action is different from that of its close chemical analogs, rapamycin and temsirolimus.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Torisel (temsirolimus) / Pfizer
Trial completion date, Surgery, Metastases: Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - Mar 12, 2024
P1, N=22, Active, not recruiting,
- |||||||||| Torisel (temsirolimus) / Pfizer
Trial completion date, Trial primary completion date, Metastases: Dasatinib, Temsirolimus, and Cyclophosphamide in Treating Patients With Advanced, Recurrent, or Refractory Solid Tumors (clinicaltrials.gov) - Mar 2, 2024
P1, N=14, Active, not recruiting,
Taken together, these results illustrate the translational value of the Jeko-1-luc model and provides a platform for evaluating novel treatment modalities for mantle cell lymphoma. Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
- |||||||||| Torisel (temsirolimus) / Pfizer
Retrospective data, Journal, Real-world evidence, Real-world: Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center. (Pubmed Central) - Feb 28, 2024
Factors leading to non-adherence to MTB recommendations in other patient cases included informed patient refusal, rapid deterioration, stable disease, or use of alternative targeted but biomarker-agnostic treatments such as antibody-drug conjugates or checkpoint inhibitors. Despite a remarkable rate of actionable mutations in HPV-related gynecologic malignancies at our institution, immediate implementation of biomarker-guided targeted treatment recommendations remained low, and access to targeted treatment options after MTB discussion remained a major challenge.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Torisel (temsirolimus) / Pfizer, Yervoy (ipilimumab) / Ono Pharma, BMS
Biomarker, Clinical, Clinical protocol, Observational data, Retrospective data, Review, Journal, PD(L)-1 Biomarker, IO biomarker: Deep response to a combination of mTOR inhibitor temsirolimus and dual immunotherapy of nivolumab/ipilimumab in poorly differentiated thyroid carcinoma with PTEN mutation: a case report and literature review. (Pubmed Central) - Feb 19, 2024
However, no clear association between the efficacy of mTOR inhibitors and specific histologies or genetic mutations has been established. Future studies are warranted to elucidate these associations.
- |||||||||| Journal, Adverse events, Real-world evidence, Real-world: Drug-induced interstitial lung disease: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System from 2004 to 2021. (Pubmed Central) - Jan 31, 2024
We also found some drugs without DILD in the labels, such as amiodarone, temsirolimus, and ursodiol...For example, the United States and France reported more cardiovascular agents, whereas Canada reported more antirheumatic agents. We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Resistance to PRMT5-targeted therapy in mantle cell lymphoma. (Pubmed Central) - Jan 9, 2024
We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies. Bulk RNA sequencing of resistant cell lines and PDX relative to sensitive or short-term-treated cells, respectively, highlighted shared upregulation of multiple pathways including mechanistic target of rapamycin kinase [mTOR] signaling (P
- |||||||||| Biomarker, Journal, Gene Signature, IO biomarker: A novel prognostic and therapeutic target biomarker based on complement-related gene signature in gastric cancer. (Pubmed Central) - Jan 9, 2024
Besides, compared to the low-risk group, there were higher expressions of most immune checkpoint genes and HLA genes in the high-risk group, and the high-risk patients showed higher sensitivity to the chemotherapy and targeted drugs (axitinib, dasatinib, pazopanib, saracatinib, sunitinib and temsirolimus). The novel CRG signature may act as a reliable, efficient tool for prognostic prediction and treatment guidance in future clinical practice.
- |||||||||| Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Trial completion date, Combination therapy, Metastases: A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) (clinicaltrials.gov) - Dec 26, 2023
P1, N=140, Active, not recruiting,
Therefore, bazedoxifene could be effectively applied as a therapeutic drug for human osteosarcoma in the future. Trial completion date: Dec 2023 --> Dec 2024
- |||||||||| Zolinza (vorinostat) / Merck (MSD), Torisel (temsirolimus) / Pfizer
Enrollment closed, Trial completion date, Trial primary completion date, Epigenetic controller, Metastases: Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer (clinicaltrials.gov) - Dec 19, 2023
P1, N=249, Active, not recruiting,
Trial completion date: Dec 2023 --> Dec 2024 Unknown status --> Active, not recruiting | Trial completion date: May 2021 --> Aug 2025 | Trial primary completion date: May 2020 --> Aug 2025
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Yervoy (ipilimumab) / Ono Pharma, BMS
P2 data, Journal, Metastases: Tailored immunotherapy approach with nivolumab with or without nivolumab plus ipilimumab as immunotherapeutic boost in patients with metastatic renal cell carcinoma (TITAN-RCC): a multicentre, single-arm, phase 2 trial. (Pubmed Central) - Nov 6, 2023
P2
However, overall efficacy seemed inferior when compared with approved upfront nivolumab plus ipilimumab. For second-line treatment, nivolumab plus ipilimumab could be a rescue strategy on progression with approved nivolumab monotherapy.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal, Immunomodulating: Temsirolimus is a promising immunomodulatory agent for enhanced transplantation outcomes. (Pubmed Central) - Nov 5, 2023
For second-line treatment, nivolumab plus ipilimumab could be a rescue strategy on progression with approved nivolumab monotherapy. Temsirolimus exhibited potent immunosuppressive effects, emerging as a strong candidate to mitigate organ transplant rejection.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: PECAM-1 mediates temsirolimus-induced increase in neutrophil transendothelial migration that leads to lung injury. (Pubmed Central) - Nov 3, 2023
Furthermore, we demonstrated that temsirolimus-induced neutrophil transendothelial migration was mediated by platelet endothelial cell adhesion molecule-1 (PECAM-1) in both in vitro and in vivo experiments. Collectively, these findings highlight that temsirolimus induces endothelial barrier dysfunction via PECAM-1-dependent pathway both in vitro and in vivo, ultimately leading to neutrophil infiltration and subsequent pulmonary injury.
- |||||||||| Torisel (temsirolimus) / Pfizer, Sutent (sunitinib) / Pfizer
Trial completion date, Metastases: A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours (clinicaltrials.gov) - Nov 3, 2023
P2, N=137, Active, not recruiting,
Collectively, these findings highlight that temsirolimus induces endothelial barrier dysfunction via PECAM-1-dependent pathway both in vitro and in vivo, ultimately leading to neutrophil infiltration and subsequent pulmonary injury. Trial completion date: Sep 2023 --> Jan 2024
- |||||||||| Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (Grand Hyatt - Grand Hall B) - Nov 3, 2023 - Abstract #ASH2023ASH_3168;
P
In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7R ALT ), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3K ALT )...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Resistance to PRMT5 Targeted Therapy in Mantle Cell Lymphoma. (Pubmed Central) - Oct 2, 2023
Single cell RNA sequencing analysis demonstrated a strong shift in global gene expression with upregulation of mTOR signaling in resistant MCL PDX samples. Targeted blockade of mTORC1 with temsirolimus overcame the PRMT5 inhibitor resistant phenotype, displayed therapeutic synergy in resistant MCL cell lines, and improved survival of a resistant PDX.
- |||||||||| Trial completion, Enrollment change, Trial completion date, Trial primary completion date: NCT Neuro Master Match - N (clinicaltrials.gov) - Sep 28, 2023
P1/2, N=228, Completed,
In the MEL001 trial, a biomodulatory treatment showed substantial antitumor effects with a significant advantage over DTIC concerning DCR and mTTP while displaying a manageable safety profile. Recruiting --> Completed | N=350 --> 228 | Trial completion date: Sep 2024 --> Feb 2023 | Trial primary completion date: Sep 2023 --> Feb 2023
- |||||||||| Torisel (temsirolimus) / Pfizer
Review, Journal: The Role of mTOR in B Cell Lymphoid Malignancies: Biologic and Therapeutic Aspects. (Pubmed Central) - Sep 28, 2023
This review is mainly focused on the PI3K/v-akt/mTOR pathway-related oncogenic mechanisms in B cell NHLs with an emphasis on common B cell lymphoma types [diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL)]. Furthermore, it summarizes the literature regarding the clinical applications of the mTOR inhibitors temsirolimus and everolimus in B cell NHLs, which have been tested in a range of clinical trials enrolling patients with B cell malignancies, either as monotherapy or in combination with other agents or regimens.
- |||||||||| Torisel (temsirolimus) / Pfizer, Sutent (sunitinib) / Pfizer
Trial completion, Metastases: Phase II Study of Alternating Sunitinib and Temsirolimus (clinicaltrials.gov) - Sep 21, 2023
P2, N=37, Completed,
Although promising, further in vitro and in vivo studies are needed to confirm their potential use for the therapy of candidiasis and possibly other fungal infections. Active, not recruiting --> Completed
- |||||||||| Avastin (bevacizumab) / Roche, Torisel (temsirolimus) / Pfizer
P2 data, Journal, Metastases: A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors. (Pubmed Central) - Sep 17, 2023
P2
Three deaths occurred in the study, of which two were due to treatment-related bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.
- |||||||||| Avastin (bevacizumab) / Roche, Torisel (temsirolimus) / Pfizer
P2 data, Journal, Metastases: A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors. (Pubmed Central) - Sep 13, 2023
P2
Three deaths occurred on study, with 2 treatment-related fatal bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.
- |||||||||| Torisel (temsirolimus) / Pfizer
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Metastases: Dasatinib, Temsirolimus, and Cyclophosphamide in Treating Patients With Advanced, Recurrent, or Refractory Solid Tumors (clinicaltrials.gov) - Sep 5, 2023
P1, N=14, Active, not recruiting,
This method is fast, accurate and reliable, suitable for quantitative detection of mTOR inhibitors in human plasma. Recruiting --> Active, not recruiting | N=36 --> 14 | Trial completion date: Oct 2022 --> Oct 2023 | Trial primary completion date: Oct 2022 --> Oct 2023
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