omipalisib (GSK2126458) / GSK - LARVOL DELTA

Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Omipalisib reduces hyperphosphorylated tau protein by modulating mTOR-autophagy pathway. (PubMed, PLoS One) - "Overall, these results show that omipalisib decreases the expression of p-tau by modulation mTOR-autophagy pathway, resulting in the amelioration of spatial memory deficits. This study highlighted the potential of omipalisib as a candidate treatment for tauopathies."

Journal • CNS Disorders • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=96 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

IO biomarker • Trial completion date • Oncology • Solid Tumor • BCL2L2 • KRAS • NRAS

Genetic alterations and pharmacological response profiles from 10 cervical cancer cell lines (AACR 2024) - "All CLs were sensitive to Bortezomib, Omipalisib and Palbociclib. A large spectrum activity to Vorinostat, (HDAC inhibitor) in line with frequent (sensitizing) LoF alterations in epigenetic suppressor genes, contrasted with a selective response to other well-known CC drugs: Methotrexate, Gemcitabine, Sorafenib. Three out of CL were highly sensitive to APR246 (Eprenetapopt) as single agent. A string of LoF alterations (CSMD2/CSMD3, ZNF717, CDC27) had been previously associated with poor response to radiation or to chemo-radiation, in tumors and are present in most CLs which are derived from resistant tumors. Future objectives are to validate the present biomarker findings in the context of a clinical platform trial."

Preclinical • Cervical Cancer • Oncology • Solid Tumor • CDC27 • CSMD3 • OSBPL1A

Identifying novel vulnerabilities in clear cell sarcoma through functional and genomic screening (AACR 2025) - "These findings offer new insights into actionable vulnerabilities in CCSA, with PI3K/mTOR inhibitors showing potential for therapeutic development. Future studies will investigate synergistic combinations to further optimize treatment efficacy and validate further vulnerabilities identified by our dual screening approach."

IO biomarker • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ATF1 • CHEK1 • CREB1 • EWSR1 • HSPA5 • MCL1 • SOX10

Navitoclax, a Bcl-2/xL inhibitor, and YM155, a survivin inhibitor, in combination with carboplatin effectively inhibit ovarian cancer tumor growth (AACR 2025) - "Initial results showed that Omipalisib, Verteporfin, CA3, Mitoxantrone, Navitoclax, Venetoclax and YM155 had significant single drug activity in either the ALDH low or both the ALDH low/high cell populations... Our results suggest that the combination of Navitoclax/YM155/carboplatin has promise as a therapy for the treatment of OvCa."

Combination therapy • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • CA3

Pharmacoscopy in soft tissue sarcoma, a single-cell ex vivo drug response testing platform (Sarcoma-RC 2026) - "Treatment with the PI3K/mTOR inhibitors omipalisib and copanlisib significantly improved survival (P = 0.027 and P = 0.036, respectively) and reduced tumor growth, compared to vehicle treatment. Legal entity responsible for the study The authors. Funding Iten Kohaut Stiftung."

Preclinical • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2026 ➔ Feb 2027

Trial completion date • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Follicular Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF • HRAS • KRAS • NRAS

Modulating metabolic signatures to mitigate cabozantinib resistance in FLT3-ITD acute myeloid leukemia cell models. (PubMed, Cell Death Discov) - "In addition to resistance to cabozantinib, they also exhibited resistance to FDA-approved sorafenib and quizartinib with substantial increases in IC50...Moreover, both omipalisib and radicicol exhibited synergistic effects with cabozantinib, highlighting their therapeutic potential. Overall, we identified metabolic dysregulation as a hallmark of cabozantinib resistance and suggested that targeting metabolic vulnerabilities with PI3K/mTOR or HSP90 inhibitors could be an option to mitigate drug resistance."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • CDC37 • FLT3 • GAPDH • STAT5

Gene Expression-Based Drug Repurposing Predicted GSK-2126458 and KU-0060648 as Candidate Small Molecules for Glioblastoma Multiforme Treatment. (PubMed, Biotechnol Bioeng) - "It was identified that two FDA-approved drugs, GSK-2126458/Omipalisib (TF-IDF value = 0.019) and KU 0060648/trihydrochloride (TF-IDF value = 0) and vorinostat (TF-IDF value = 0.29), which is frequently studied in GBM may be promising candidates for GBM. GSK-2126458 drug molecule showed the lowest IC50 value with 0.40 µM and triggered necrosis with 26.6% PI positive cell labeling. Further in vitro and in vivo validation of both small molecules may provide new treatment options for GBM."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

INVESTIGATING OMIPALISIB AS A DUAL TOR COMPLEX 1/ TOR COMPLEX 2 INHIBITOR TO EXTEND YEAST LONGEVITY (WRMC 2026) - "Purpose of Study: Rapamycin extends longevity of diverse species, from yeast to non-human primate models through selective inhibition of the TOR complex 1 (TORC1). This work will provide the first evaluation of the effect of omipalisib on yeast aging. By integrating lifespan assays and genetic suppression analyses, the study will explore the contributions of TORC1 and TORC2 on longevity. The findings may guide the development of new therapeutic strategies for promoting longevity pathways in higher eukaryotes."

NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov) - P1/2 | N=75 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

IO biomarker • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BCL2

Estimation of the metabolic stability of omipalisib in human liver microsomes employing an ultra-fast UPLC-MS/MS approach: in silico screening for structural alarms and metabolic lability. (PubMed, Anal Methods) - "OMP and duvelisib (internal standard) were evaluated using an SB-C18 column. In silico analysis indicates that slight structural modifications to the methoxy group or the pyridazine ring in the process of drug design may increase the safety profile and metabolic stability of new derivatives compared with those of OMP. The integrated in vitro/in silico approach provides a resource-efficient strategy for preliminary metabolic screening and advancing new therapeutic developments aimed at enhancing metabolic stability."

Journal • Oncology

A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies. (PubMed, Cell Commun Signal) - "Together, our findings revealed shared molecular features across MPN and AML, identified a prognostic gene signature for risk stratification, and provided rationale for PI3K/mTOR inhibition as a promising therapeutic strategy in myeloid malignancies."

Gene Signature • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • CDCP1

Patient-Derived Xenograft Mouse Model of a Rare Gynecologic Malignancy: Personalized Medicine for the Treatment of Mesonephric-Like Adenocarcinoma. (PubMed, Cureus) - "We established a PDX model of MLA to facilitate personalized treatment for rare tumors."

Journal • Preclinical • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer • PIK3CA

Modulating Metabolic Reprogramming By Phosphoglycerate Dehydrogenase (PHGDH) Inhibitors in Omipalisib-Refractory AML (ASH 2023) - "The OCI-AML3-R cell line was the most refractory one and showed cross-resistance to another PI3K/mTOR inhibitor dactolisib and multi-tyrosine kinase inhibitor dasatinib, in addition to omipalisib. Transcriptomic and metabolomic analyses revealed that OCI-AML3-R upregulated PPP and SSP, leading to increased nucleotide synthesis, which contribute cell growth and survival. Targeting PHGDH could significantly suppress omipalisib-refractory in AML and may have implications for future clinical trials."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABCB1 • ABCC1 • ABCC2 • ABCG2 • MTHFD2 • PAICS • PHGDH • PSAT1 • SHMT2

Construction of a Myeloid Gene Signature Revealing Novel Therapeutic Targets for Myeloid Malignancies (ASH 2024) - "Omipalisib treatment significantly ameliorated features of myeloid malignancies including splenomegaly and leukocytosis which were both significantly reduced following 4 weeks of treatment, without affecting body weight.In summary, our MR analyses reveal that MPN predicts the risk of AML and enabled the construction of a novel myeloid signature which risk stratified AML patients across two different cohorts. We further demonstrate shared activation of PI3K/AKT/mTOR pathway across myeloid malignancies, with in vitro and in vivo data providing a rationale for therapeutic targeting of PI3K/AKT/mTOR pathway in these diseases."

Gene Signature • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • CDCP1

Trametinib With or Without Whole Brain Radiation Therapy in Treating Patients With Brain Metastases (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Oncology • Solid Tumor

ADVL1521: Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Genetic Disorders • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Neurofibromatosis • Oncology • Solid Tumor • NF1 • PTPN11

Targeting serine metabolism vulnerability in omipalisib-resistant acute myeloid leukemia with phosphoglycerate dehydrogenase inhibitors. (PubMed, Biomed Pharmacother) - "Furthermore, we found that, like OCI-AML cells, the exportin 1 (XPO1) inhibitors selinexor and eltanexor significantly induced cell cycle arrest and reduced PHGDH expression in OCI-AML3-OR cells. Therefore, treatment with PHGDH inhibitors could be a therapeutic strategy for refractory AML to PI3K/mTOR inhibitors. Relevant clinical trials are warranted."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PHGDH • XPO1

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=6452 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Biomarker • Trial completion date • Trial primary completion date • Bladder Cancer • Brain Cancer • Breast Cancer • Cervical Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hematological Malignancies • Hormone Receptor Positive Breast Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Thyroid Gland Carcinoma • Uterine Cancer • CD4 • MSI

PLEKHG7 Expression: A Biomarker for Prognosis and Targeted Therapy in Diffuse Large B-cell Lymphoma. (PubMed, Protein Pept Lett) - "PLEKHG7 is significantly overexpressed in DLBCL and independently predicts poor prognosis. Its association with key oncogenic pathways and drug resistance underscores its potential as both a prognostic biomarker and a therapeutic target, warranting further functional validation."

Biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PLEK

Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Completed ➔ Active, not recruiting | Trial completion date: Sep 2017 ➔ Jul 2026

Enrollment closed • Trial completion date • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Changes in Melanoma Cell Morphology Following Inhibition of Cell Invasion by Third-Generation mTOR Kinase Inhibitors. (PubMed, Int J Mol Sci) - "The study used mTOR kinase inhibitors: Everolimus and Torkinib; dual PI3K/mTOR inhibitors BEZ-235 and Omipalisib; and the mTORC1/2 inhibitor OSI-027. These compounds were used both as monotherapy and in combination with the MEK1/2 inhibitor AS-703026...The morphology of cells also changed significantly: their thickness, volume, roughness, convexity of shape, and irregularity, which may be a good diagnostic and prognostic factor for the response to treatment. Our studies to date on the effect of three generations of mTOR kinase inhibitors on the inhibition of the invasion process, the activation of apoptosis, and the reduction in cell proliferation suggest that they may be an important target for anticancer therapy."

Journal • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • MMP2 • MMP9