everolimus / Generic mfg. - LARVOL DELTA

Optim.AI™ 2.0: Functional precision platform for identifying effective immunotherapy combinations in DLBCL (ASH 2025) - "PBMCs were added to tumor cells at a fixed effector-to-target ratio, and Optim.AI 2.0 combinatorial drug sensitivity testing plates were applied to the co-culture system, with up to 12 FDA-approved drugs, including monoclonal antibodies (rituximab, obinutuzumab), antibody-drug conjugates (polatuzumab), bispecific antibodies (epcoritamab, glofitamab), targeted small-molecule inhibitors (venetoclax, everolimus, zanubrutinib), and cytotoxic chemotherapies (gemcitabine, oxaliplatin, cyclophosphamide, doxorubicin). This study demonstrates the feasibility of Optim.AI™ 2.0, an enhanced co-culture-based platform which provides a physiologically relevant and scalable approach to functionally evaluate immunotherapy drug sets. With further validation, Optim.AI™ 2.0 holds strong potential to support clinical decision-making and expand the use of immunotherapies in DLBCL."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Sarcoma • Solid Tumor

Early detection of emerging safety signals in GVHD prophylaxis agents using a 12-year faers "slope-watch" approach (ASH 2025) - "In addition to tacrolimus and cyclosporine, contemporary prophylaxis regimens employ sirolimus and everolimus, mycophenolate mofetil, methotrexate, post-transplant cyclophosphamide (PTCy), JAK inhibitors (ruxolitinib, baricitinib, tofacitinib), co-stimulation blockade with abatacept, gut-homing integrin antagonism via vedolizumab, and the ROCK2 inhibitor belumosudil. Sequential IC-Δ offers a robust, forward-looking pharmacovigilance framework that identifies adverse event acceleration 12–24 months before regulatory action. By emphasizing directional change and incorporating a simple confidence approximation, this approach enhances early signal detection in large safety datasets. Integration with electronic health records, regulatory pipelines, and interactive dashboards could further streamline horizon scanning and improve patient safety in GVHD prophylaxis."

Clinical • Bone Marrow Transplantation • CNS Disorders • Cytomegalovirus Infection • Dyslipidemia • Graft versus Host Disease • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Metabolic Disorders • Pneumonia • Rare Diseases • Respiratory Diseases • Septic Shock

A US real-world analysis of demographics, transplant patterns, and survival outcomes in posttransplant lymphoproliferative disorder (PTLD) (ASH 2025) - "Other agents includedprednisone (6.2%), cyclosporine (5.8%), sirolimus (5.8%), dexamethasone (4.8%), azathioprine (3.1%),methylprednisolone (1.9%), everolimus (0.7%), ibrutinib (0.6%), ruxolitinib (0.6%), mycophenolate(0.3%), basiliximab (0.2%), and thymoglobulin (0.1%).Extranodal, bone marrow, and CNS involvement were present in 29.5%, 1.9%, and 1.8% of cases,respectively...Median OSfor heart transplant recipients was 2730 days, and for those who underwent HSCT, 2643 days.Regarding treatment, only 10 patients received bispecific antibodies (glofitamab, epcoritamab, ormosunetuzumab) and only 23 patients received CAR-T therapy. This study represents one of the largest real-world analyses of PTLD in adult patients inthe US, utilizing the TriNetX dataset spanning over three decades. This study represents one of the largest real-world analyses of PTLD in adult patients inthe US, utilizing the TriNetX dataset spanning over three decades. Improvement in OS in more recentyears..."

Clinical • Post-transplantation • Real-world • Real-world evidence • Bone Marrow Transplantation • Epstein-Barr Virus Infections • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Solid Organ Transplantation • Transplantation

Distinct mTOR- and CDK1-regulated translation circuits sustain FLT3-mutated AML survival under therapy (ASH 2025) - "This study aims to define how AMLcells maintain translation despite mTORC1 inhibition and whether this contributes to resistance againstFLT3- and mTORC1-targeted therapies.MethodsPulse SILAC was performed on MOLM14 cells (FLT3-ITD AML cell line) to track nascent protein synthesisover a 5-hour window starting 4 hours after treatment, using Everolimus to inhibit mTORC1 and RO-3306to inhibit CDK1...Importantly, our analyses reveal novel,noncanonical roles for CDK1 beyond its established function in cell cycle regulation in maintaining theprotein expression of mRNA splicing, transcript maturation, and nuclear export components, highlightinga critical role beyond cell cycle control. These findings expose a critical vulnerability in the translationaldependence of FLT3-ITD AML cells, highlighting the need to understand how translation is sustainedindependently of mTOR to anticipate resistance and guide future FLT3i and mTORC1i combinationtherapies aimed at preventing relapse."

Acute Myelogenous Leukemia • CDK1 • FLT3

Clinical effectiveness of everolimus plus somatostatin analogues in advanced neuroendocrine tumors: A retrospective real-world study (ESMO Asia 2025) - "Patients received either everolimus alone or in combination with a somatostatin analogue (lanreotide 120 mg Q4W or octreotide LAR 30 mg Q4W). This real-world study suggests that combining everolimus with a somatostatin analogue may improve PFS over monotherapy in advanced NETs, although statistical significance was not reached. The observed trend aligns with clinical trial data and supports the potential benefit of combination therapy in practice. No significant difference was found between lanreotide and octreotide, indicating both agents may be interchangeable when used with everolimus."

Metastases • Real-world • Real-world evidence • Retrospective data • Neuroendocrine Tumor • Oncology • Solid Tumor

The activity of SIM0270 alone or in combination with everolimus or palbociclib in ER-positive, HER2-negative breast cancer patients with brain metastases (ESMO Asia 2025) - P1 | "Observed encouraging clinical benefits support further investigation for the use of SIM270 in combination with palbociclib or everolimus in ER-positive, HER2-negative breast cancer patients with BM."

Clinical • Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Fruquintinib monotherapy as second-line (2L) treatment in locally advanced or metastatic renal cell carcinoma (RCC): Results from phase II part of FRUSICA-2 (ESMO Asia 2025) - P2/3 | "Background: FRUSICA-2 is a randomized, open-label, active-controlled phase 2/3 study (NCT05522231) designed to evaluate the efficacy and safety of Fruquintinib (F) + Sintilimab versus Axitinib or Everolimus monotherapy for 2L treatment of RCC. Results from this F monotherapy of the FRUSICA-2 indicated a comparable anti-tumor efficacy compared with other 2L VEGFR-TKI monotherapies, along with a manageable safety profile in 2L RCC pts after first-line VEGFR-TKI therapy."

Clinical • Metastases • Monotherapy • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Molecular analysis to predict the clinical benefit of everolimus in gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). (ASCO-GI 2026) - "The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Biomarker • Clinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Everolimus or lanreotide: Who is the true winner for GI-NETs? (ASCO-GI 2026) - "The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Clinical outcomes of [177Lu]Lu-DOTA-TATE (177Lu-DOTATATE) vs everolimus (EVE) in managing patients (pts) with gastroenteropancreatic-neuroendocrine tumors (GEP-NETs): Real-world analysis of the PRIME initiative. (ASCO-GI 2026) - "Funded by Novartis Pharmaceuticals Corporation The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Clinical data • Real-world • Real-world evidence • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Zanzalintinib versus everolimus in patients with previously treated advanced neuroendocrine tumors: The phase 2/3, randomized STELLAR-311 trial. (ASCO-GI 2026) - P2/3 | "Funded by Exelixis, Inc. Clinical Trial Registration Number: NCT06943755 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2/3 data • Gastrointestinal Cancer • Oncology • Solid Tumor

Patient-reported outcomes in LITESPARK-005: a timely step toward patient-centered metrics in advanced renal cell carcinoma. (PubMed, Chin Clin Oncol) - No abstract available

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

THE RAF/MEK INHIBITOR VS-6766 SHOWS EFFICACY IN RAS-MUTANT PEDIATRIC PRECLINICAL XENOGRAFT MODELS- A REPORT FROM THE PEDIATRIC PRECLINICAL IN VIVO TESTING CONSORTIUM (CTOS 2025) - "To evaluate drug combinations, RMS PDXs were treated with VS-6766 in doublet with 14 other drugs targeting additional areas of the MAPK/ERK pathway along with untreated control, VS-6766 alone, and vincristine + irinotecan (standard of care) for a total of 17 treatment groups...In combination testing, survival advantage was most notable when VS-6766 was combined with VS-4718 (FAK), everolimus (mTOR), copanlisib (PI3Kδ/α), capivasertib (AKT), BBP-398 (SHP2) and LY3023414 (PI3K) compared to VS-6766 alone. VS-6766 exhibited antitumor activity across several pediatric cancers... VS-6766 exhibited antitumor activity across several pediatric cancers. As single agent, there was activity in the majority of solid tumor models tested with prolongation of time on study and stabilization of disease. Solid tumor models harboring RAS mutations appear more likely to respond, although limited non-mutant models were tested."

Preclinical • Hematological Malignancies • Leukemia • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • HRAS • KRAS • NF1 • NRAS • PIK3CD

Sequencing PIK3CA, AKT and mTOR Inhibitors in HR+/HER2- Metastatic Breast Cancer: A Real-World Retrospective Analysis (SABCS 2025) - "Approved agents—everolimus (mTOR inhibitor), alpelisib (PIK3CA inhibitor), and capivasertib (AKT inhibitor)—have demonstrated median progression-free survival (mPFS) ranging from 5.5 to 7.3 months in patients previously treated with CDK4/6 inhibitors. Our findings support the consideration of sequencing pathway inhibitors regardless of tolerance to the first agent. These results reinforce sequential PI3K/AKT/mTOR inhibition as a viable strategy in modern metastatic breast cancer care, though prospective studies are needed to validate this approach in pretreated populations."

Metastases • Real-world • Real-world evidence • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Poor response to systemic therapy upon progression on cyclin dependent kinase 4/6 inhibitors in HR+ Inflammatory Breast Cancer (SABCS 2025) - "RESULTS Among N = 33 patients evaluated, upon progression on standard of care CDKI and endocrine directed therapy (ET) combinations, patients received the following therapies with median ToT (months (min-max ToT)), respectively: capecitabine (N = 7; 3 (2-5)), everolimus/ET (N = 6, 3 (1-4)), Abraxane (N = 3, 3(2-10)), Eribulin (N = 2, 2.5(2-3)), capivasertib/fulvestrant (N = 1, 6(6)), taxol (N = 1, 5(5)), elacestrant (N = 1, 3(3)), fulvestrant (N = 1, 3(3)), tamoxifen (N = 1, 1(1)), intrathecal topotecan (N = 1, 1(1)), non standard/clinical trial (N = 4, 2.5(1-4)). CONCLUSION Patients with metastatic HR+ IBC demonstrate poor response to ET and cytotoxic chemotherapies upon progression on first line standard CDKI/ET, with a disproportionately high rate of death occurring in the first line setting due to advanced disease. Given previously reported low ToT on CDKI/ET in the first line and high incidence of brain relapse in this population, clinical trial design utilizing..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • HER-2

Circulating microRNA and cytokine signatures associated with interstitial lung disease in patients treated with trastuzumab deruxtecan. (SABCS 2025) - "This is the first study to characterize circulating microRNA and cytokine profiles associated with ILD in patients treated with trastuzumab deruxtecan. Distinct inflammatory and fibrotic signatures differentiated ILD cases from matched controls, with consistent associations observed between selected miRNAs and immunemediators. A subset of these alterations was also found in ILD cases attributed to everolimus or abemaciclib."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • CCL2 • CXCL10 • HAVCR2 • HER-2 • IFNG • IL2 • IL6

Gedatolisib, a multi-target PI3K/AKT/mTOR (PAM) inhibitor, plus fulvestrant with or without palbociclib for second-line (2L) treatment of patients with HR+/HER2-/PIK3CA-wild type (WT) advanced breast cancer (ABC): updated results from the randomized, phase 3 VIKTORIA-1 trial (SABCS 2025) - "In preclinical studies, gedatolisib demonstrated superior potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus, regardless of PI3K-pathway mutation status, and combinations of gedatolisib + fulvestrant, with and without palbociclib, were active in treatment-naive and resistant cell lines. These updated results support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of patients with HR+/HER2-/PIK3CA WT ABC."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Strategic trimodal therapy enhances radiation-induced abscopal response in renal cancer. (PubMed, J Transl Med) - "This study presents a novel and effective strategy to induce the abscopal effect through a synergistic combination of targeted drug delivery, radiotherapy, and immunotherapy. The approach offers strong translational potential for improving radioimmunotherapy outcomes in renal and potentially other immunogenic cancers."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD163 • CD8 • IL2

High-grade gastro-entero-pancreatic neuroendocrine neoplasms: an overlooked population in interventional clinical trials. A systematic review. (PubMed, Crit Rev Oncol Hematol) - "High-grade GEP-NENs (particularly NET G3) remain an overlooked population in interventional studies. Progress in precision medicine requires the identification of molecular biomarkers to guide individualized therapy."

IO biomarker • Journal • Review • Endocrine Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

A Study to Evaluate Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics

Molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG): CONNECT TarGeT (Targeted pediatric HGG therapy) trial in progress (WFNOS 2025) - P, P2 | "The following TarGeT treatment arms (most involving upfront radiotherapy), are open or soon to open, selected based on prevalence of targets in HGG/DIPG, relevant pre-clinical and clinical data, established pediatric safety data, and prioritizing combinations: (A) ribociclib and everolimus (target: cell cycle or PI3K//mTOR pathway alterations) [NCT05843253], (A-2) ribociclib and temozolomide (H3G34 mutation) (B) tovorafenib (MAPK pathway alterations), (D) olutasidenib and temozolomide (IDH1 mutation) [NCT06161974], (F) nivolumab and relatlimab (high tumor mutational burden, mismatch repair deficiency), (L) lorlatinib (+/- chemotherapy or radiation) (ROS1, ALK fusion). Development of additional treatment arms is underway, with possibility of incorporating new arms as supporting data allows."

Clinical • P2 data • Tumor mutational burden • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Pediatrics • Solid Tumor • ALK • IDH1 • ROS1 • TMB

Molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG): CONNECT TarGeT (Targeted pediatric HGG therapy) trial in progress (SNO 2025) - P, P2 | "The following TarGeT treatment arms (most involving upfront radiotherapy), are open or soon to open, selected based on prevalence of targets in HGG/DIPG, relevant pre-clinical and clinical data, established pediatric safety data, and prioritizing combinations: (A) ribociclib and everolimus (target: cell cycle or PI3K//mTOR pathway alterations) [NCT05843253], (A-2) ribociclib and temozolomide (H3G34 mutation) (B) tovorafenib (MAPK pathway alterations), (D) olutasidenib and temozolomide (IDH1 mutation) [NCT06161974], (F) nivolumab and relatlimab (high tumor mutational burden, mismatch repair deficiency), (L) lorlatinib (+/- chemotherapy or radiation) (ROS1, ALK fusion). Development of additional treatment arms is underway, with possibility of incorporating new arms as supporting data allows."

Clinical • P2 data • Tumor mutational burden • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • High Grade Glioma • Pediatrics • Solid Tumor • ALK • IDH1 • ROS1 • TMB

Integrated proteomic analysis identifies TYMS-dependent AMPK-mTOR signaling in pancreatic neuroendocrine tumors. (PubMed, iScience) - "TYMS levels also impact the efficacy of everolimus, an FDA-approved mTOR inhibitor for patients with PanNET, underscoring the clinical significance of our findings. In summary, our study uncovers a new role of TYMS linking nucleotide metabolism to growth signaling pathways via the regulation of the AMPK-mTOR axis."

Journal • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • MEN1 • TYMS

Second-line therapies of Metastatic Renal Cell Carcinoma (mRCC) after 1st line immune-combinations (ICI-combos) (Meet-URO 33 study) (EMUC 2025) - "According to the ICI-combo type, 36% of patients treated with Pembrolizumab + Axitinib, 32% with Nivolumab + Ipilimumab, 11% with Nivolumab + Cabozantinib and 9% with Pembrolizumab + Lenvatinib started a 2nd line therapy...Drug combinations (Lenvatinib + Everolimus/Belzutifan) rise as emerging therapies, especially in younger and prognostically unfavorable patients. Further survival and response analyses are planned."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor