temsirolimus / Generic mfg. - LARVOL DELTA

Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (ASH 2023) - 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 (IL7RALT), 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 (PI3KALT)...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."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • ATM • BCL2 • DNMT3A • IDH1 • IDH2 • IL7R • PHF6 • SRSF2 • TET2 • TP53

SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer. (PubMed, Nat Commun) - "mTOR inhibitors including everolimus and temsirolimus have been approved by US FDA for treatment of clear cell renal cell carcinoma (ccRCC) in clinic. Treatment with a NEK7 proteolysis-targeting chimera (PROTAC) effectively inhibits aberrant p70S6K activation and overcame everolimus resistance in ccRCC cells in vitro and in mice. Our findings uncover a function switch of ZMYND8 driven by overexpressed SPOP as a key mechanism that causes mTOR inhibitor resistance and nominate NEK7 as a potential target of thwarting mTOR inhibitor resistance in ccRCC."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Targeted Protein Degradation • SPOP • ZHX2 • ZMYND8

Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas. (PubMed, Haematologica) - P1/2 | "ORR for cHL patients in the exploratory cohort, most of whom had relapsed after both brentuximab vedotin and ASCT, was 80% (35% CR). Combination therapy with TEM/LEN was feasible and demonstrated encouraging activity in heavily-pretreated lymphomas, particularly in relapsed/refractory cHL. ClinicalTrials.gov identifier: NCT01076543."

Clinical • Journal • P1/2 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Accessing BTK Inhibitors and Other Novel Therapies for Mantle Cell Lymphoma: Are We All Invited to the Party? (SOHO 2024) - "In the phase 3 RAY trial,2 ibrutinib led to better responses and significant improvements in progression-free survival (PFS) and tolerability versus temsirolimus in patients with R/R MCL...In the SHINE trial,3 the combination of ibrutinib with bendamustine and rituximab for 6 cycles, followed by rituximab maintenance and ibrutinib until progression, led to an unprecedented PFS of 80.6 months in patients not eligible for ASCT...Second-generation BTK inhibitors have also been approved for R/R MCL, including acalabrutinib and zanubrutinib with a more favorable safety profile. In first line therapy, the results of bendamustine, rituximab, and acalabrutinib are expected to be presented soon...Pirtobrutinib, a third-generation non-covalent BTK inhibitor has shown promising activity in MCL after exposure to covalent BTK inhibitors. Moreover, the BCL-2 inhibitors, venetoclax and sonrotoclax, have also shown activity in the post-BTK inhibitor scenario, and sonrotoclax is..."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer. (PubMed, Gynecol Oncol) - P1 | "The results of this single-center clinical trial showed that, in patients with advanced or recurrent endometrial cancer, metformin can be safely added to temsirolimus providing limited response without added safety concerns."

Journal • P1 data • Anorexia • Dyslipidemia • Endometrial Cancer • Fatigue • Hematological Disorders • Hypertriglyceridemia • Mucositis • Oncology • Renal Disease • Solid Tumor • Thrombocytopenia

Re-Evaluating Temsirolimus in Newly Diagnosed MGMT-Unmethylated Glioblastoma: A Combined Outcome, Quality-of-Life, and Biomarker Analysis of the EORTC 26082 and NOA-20/N2M2 Trials (SNO 2026) - No abstract available

Biomarker • HEOR • Brain Cancer • Glioblastoma • Solid Tumor • MGMT

Re-evaluating temsirolimus in MGMT-unmethylated glioblastoma: A combined outcome, quality-of-life, and biomarker analysis of the EORTC 26082 and NOA-20/N2M2 trials (EANO 2026) - "This cross-consortium analysis provides a multidimensional evaluation of temsirolimus in MGMT-unmethylated glioblastoma, spanning survival, toxicity, and quality-adjusted outcome. The pooled data indicate an overall survival benefit for temsirolimus over temozolomide in p-mTOR-positive disease. Notably, the recently established nuclear p-mTOR readout refines this selection beyond conventional cytoplasmic positivity, identifying the patients most likely to benefit from temsirolimus."

Biomarker • HEOR • Late-breaking abstract • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

Temsirolimus (T) in patients (pts) with solid tumors with mTOR mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. (ASCO 2022) - P2 | "Monotherapy T showed evidence of anti-tumor activity in pts with advanced solid tumors with mTOR mut. Additional study is warranted to confirm the efficacy of T in pts with mTOR mut."

Clinical • Acute Kidney Injury • Biliary Cancer • Diabetes • Dyslipidemia • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Hepatology • Hypertension • Hypertriglyceridemia • Inflammation • Leukopenia • Mucositis • Nephrology • Oncology • Pneumonia • Renal Disease • Solid Tumor • Thrombocytopenia • Uterine Cancer • mTOR

BRAINTOX: uremic toxins in chemotherapy response in the brain (EANO 2026) - "Then, U87MG cells were co-treated with p-cresyl sulfate or indoxyl sulfate and ten selected drugs in a drug screening platform (drugs: Temozolamide, Dacomitinib, Selinexor, Panobinostat, Ixazomib, AMG232, Bortezomib, Lazertinib, Temsirolimus, Carmilzomib). The uremic toxins p-cresyl sulfate and indoxyl sulfate were enriched in brain tumor tissue samples of IDH wt patients compared to IDH mut patients, validating the findings of the discovery cohort. IDH wt patients have higher levels of uremic toxins in the circulation compared to patients with IDH mutant adult-type diffuse gliomas and the toxins reach the tumor site. Further experiments shall elucidate the mechanism by which uremic toxins reach the tumor cells and whether they modulate drug responsiveness."

Brain Cancer • Diffuse Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor

Temsirolimus (T) in patients (pts) with solid tumors with PTEN mutation (mut): results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study (AACR 2023) - "T met prespecified criteria to declare a signal of activity in pts with solid tumors with PTEN mut.Table: Baseline Characteristics (N=34); Efficacy Outcomes (n=27); Toxicity Outcomes (N=34) Median (Med) age, years (range) 65 (42, 84)Female, % 14 (41)ECOG PS, % 0 13 (38) 1 18 (53) 2 3 (9)Prior systemic regimens, % 1 3 (9) 2 5 (15) ≥3 26 (77)DC rate, % (OR and SD16+) (1-sided 90% CI) 26 (15.1, 100)OR rate, % (95% CI) 7 (1, 24)Med PFS, wks (95% CI) 10 (7, 17)Med OS, wks (95% CI) 32 (13, 42)DOR, wks (n=2) 11 and 55Med duration SD, wks (n=5) 27 (24, 36)Number of pts1 with tx-related grade 3-4 AE or SAE AE2  12 (35) SAE3 6 (18)1Pts may have experienced one or more events 2 alkaline phosphatase increase, anemia, chronic kidney disease, diarrhea, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, lung infection, oral pain and all SAEs3 acute kidney injury, dyspnea,..."

Clinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • PTEN

N2M2/NOA-20: Phase I/IIa umbrella trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation. (ASCO 2024) - P1/2 | "Background: Patients with glioblastoma without MGMT promoter hypermethylation are unlikely to benefit from temozolomide (TMZ)...The alectinib and vismodegib subtrials were closed since no molecularly matching patients were accrued; the idasanutlin subtrial was closed prior to the optimal dose at nine patients at discretion of the company providing the drug... N 2 M 2 allows for elaborate molecular testing being integrated into the treatment decision and efficient determination of treatment activity for patients with newly diagnosed glioblastoma. There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients and also palbociclib in molecularly selected patients."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDK4 • CDKN2A • CDKN2B

Metabolic-pathway-based classification of tendinopathy reveals a precise therapeutic strategy targeting chondro-modulatory tenocytes. (PubMed, Bone Res) - "Notably, we identified and validated the clinical drug temsirolimus as an effective agent specifically against MPC-G in experimental models. Collectively, our study delineates the metabolic heterogeneity of tendinopathy and establishes a classification framework that enables precision medicine strategies tailored to distinct metabolic profiles."

Journal • Metabolic Disorders • HIF1A

Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: St. Jude Children's Research Hospital | Active, not recruiting ➔ Completed

Trial completion • Embryonal Tumor • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Deciphering the Leading-Edge Spatiotemporal Microenvironment of Hepatocellular Carcinoma for Targeted Drug Discovery Using SpaPred. (PubMed, Int J Mol Sci) - "Finally, integration of in silico trajectory-perturbation and pharmacogenomic drug-response analyses prioritized Oxaliplatin, Belinostat, and Temsirolimus as candidate compounds associated with LE-related transcriptional programs. These drug predictions are computational and require experimental validation. Collectively, SpaPred provides a hypothesis-generating framework for investigating spatial heterogeneity and candidate therapeutic vulnerabilities in HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • IGFBP7 • SPARC

Survival and Homeostasis of Alveolar Macrophages in Vivo Depend on mTOR Signaling. (PubMed, Am J Respir Cell Mol Biol) - "In vivo, pharmacologic mTOR inhibition with temsirolimus reproduced key features of genetic mTOR deletion, including AM depletion, apoptosis, lipid accumulation, and PAP-like pathology...In summary, these findings identify mTOR as a nonredundant, cell-intrinsic regulator of alveolar macrophage survival and function required to maintain alveolar homeostasis. This work provides experimental support for AM-intrinsic mechanisms contributing to mTOR inhibitor-associated pulmonary toxicity, including PAP."

IO biomarker • Journal • Preclinical • Respiratory Diseases • BCL2 • PPARG

A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours (clinicaltrials.gov) - P2 | N=137 | Active, not recruiting | Sponsor: Canadian Cancer Trials Group | Trial completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Adrenal Cortex Carcinoma • Hepatocellular Cancer • Oncology • Ovarian Cancer • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • NF1 • PTEN • STK11

3D co-culture model of tumor spheroid and endothelial cells unveils ccRCC aberrant vasculature and distinct sensitivity to targeted treatments. (PubMed, Angiogenesis) - "Drug testing demonstrated that temsirolimus, crizotinib, and sunitinib impaired capillary morphogenesis and tumor invasion to varying extents in monoculture, while co-culture model reduced overall drug efficacy. Importantly, ponds exhibited markedly reduced sensitivity to sunitinib compared with adjacent capillaries, suggesting that they may contribute to anti-angiogenic resistance. This study defines key features and heterogeneity of ccRCC vascular architecture and highlights ponds as candidate contributors to treatment failure and targets for future interventions."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Von Hippel-Lindau Syndrome

WIN-MTB-2024017 - WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers. (PubMed, Oncotarget) - "Her treatment history included doxorubicin and cyclophosphamide for breast cancer, Mohs surgery for basal cell carcinoma, and carboplatin and paclitaxel for ovarian cancer...The panel discussed several precision strategies, including combinations of cetuximab, niraparib, and temsirolimus; FOLFIRI with anti-EGFR inhibitors; anti-CTLA-4 and anti-PD-1 (botensilimab and balstilimab); regorafenib with anti-CTLA-4 and anti-PD-1 (ipilimumab and nivolumab); trifluridine/tipiracil with bevacizumab; regorafenib alone; aspirin for potential benefits in patients with PIK3CA mutations; therapies targeting PIK3CA and EGFR alterations; regular imaging and liquid biopsies assessments for monitoring disease progression and guide future treatment decisions; and vaccines targeting PIK3CA, STARD3 and TP53. This case underscores the complexity of managing MPC and highlights the essential role of international molecular tumor boards in generating innovative, tailored treatment recommendations..."

Biomarker • IO biomarker • Journal • Basal Cell Carcinoma • Breast Cancer • Colon Cancer • Colorectal Cancer • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Small Intestinal Carcinoma • Solid Tumor • BRCA1 • PIK3CA • TP53

Combination Chemotherapy and Bevacizumab With the NovoTTF-100L(P) System in Treating Participants With Advanced, Recurrent, or Refractory Hepatic Metastatic Cancer (clinicaltrials.gov) - P1 | N=38 | Terminated | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2026 ➔ Jul 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Jul 2026; <75% participation

Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Oncology • Solid Tumor • PIK3CA • PTEN

Simvastatin enhances the antitumor activity of temsirolimus through AMPK-associated metabolic modulation in clear-cell renal cell carcinoma. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "In vivo, combination therapy significantly suppressed tumor growth compared with monotherapy and alleviated temsirolimus-induced hypercholesterolemia without apparent toxicity. Simvastatin-induced metabolic perturbation enhances mTOR inhibition in a cell-dependent manner, supporting dual metabolic targeting as a potential therapeutic strategy in ccRCC."

Journal • Clear Cell Renal Cell Carcinoma • Dyslipidemia • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor • AMPK • FASN • FBP1 • STK11 • VHL

Drug repurposing as a promising therapeutic strategy against renal cell carcinoma. (PubMed, Cancer Chemother Pharmacol) - "This review article summarizes and shows the effectiveness and potential of repurposed drugs including metabolic and cardiovascular modulators (metformin, simvastatin), antimicrobial and antiparasitic agents (artesunate, ivermectin, ketoconazole, chloroquine, hydroxychloroquine, niclosamide, doxycycline, pentamidine), mTOR inhibitors (temsirolimus, everolimus, rapamycin), anti-inflammatory and analgesic agents (aspirin, celecoxib), and agents with other mechanisms of action (acetazolamide, disulfiram). These agents exert their anticancer effects against RCC by modulating multiple signaling pathways, including PI3K/AKT/mTOR, AMPK, JAK2/STAT3, ERK1/2, Wnt/β-catenin, and RhoA/ROCK, as well as by inducing autophagy inhibition, ferroptosis, oxidative stress, and mitochondrial dysfunction, highlighting their utility in RCC therapy and emphasizing their clinical relevance."

Journal • Review • Cardiovascular • Genito-urinary Cancer • Kidney Cancer • Metabolic Disorders • Oncology • Pain • Renal Cell Carcinoma • Solid Tumor • AMPK • CTNNB1 • JAK2 • RHOA • STAT3

Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer (clinicaltrials.gov) - P3 | N=236 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Mar 2027 ➔ Mar 2026

Trial completion • Trial completion date • Hepatoblastoma • Liver Cancer • Oncology • Solid Tumor • AFP

A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) (clinicaltrials.gov) - P1 | N=140 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Colon Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

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) - P1 | N=154 | Terminated | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Oct 2026 ➔ May 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2026 ➔ May 2026; < 75 % participation

Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Endocrine Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Gynecologic Cancers • Head and Neck Cancer • Neurofibromatosis • Oncology • Oral Cancer • Pulmonary Disease • Rare Diseases • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Thoracic Cancer • Thyroid Gland Carcinoma • Urothelial Cancer

Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Nader Sanai | N=12 ➔ 5 | Trial completion date: May 2028 ➔ Oct 2025 | Recruiting ➔ Terminated; Study terminated due to unavailability of the investigational product required to continue the study.

Enrollment change • Trial completion date • Trial termination • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • mTOR • PIK3C2B • PIK3CA • PIK3R1 • PTEN