omipalisib (GSK2126458) / GSK - LARVOL DELTA

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

Downstream Signaling Mediators of CXCL6-driven Synthesis of Collagen in Human Fibroblasts (ATS 2025) - "Doxycycline was used to induce CXCL6 expression and secretion in BJ13 cells. A panel of specific pathway inhibitors were added to cells, including SR11302 (AP1), MK2206 (AKT), SB203850 (p38), SP600125 (JNK), PD184352 (MEK), FASUDIL (ROCK/RHO), SLV2436 (MNK1/2), Omipalisib (mTOR/PI3K), Torin (mTOR), and Reparixin (CXCR1/2)... We identified that CXCL6 induces collagen production through multiple pathways including mTOR, p38, JNK and MEK. Targeting a combination of these pathways may be a potential therapeutic direction for IPF treatment."

Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CXCL6 • CXCR1 • SMAD3 • TGFB1

Navitoclax, a Bcl-2/xL Inhibitor, and YM155, a Survivin Inhibitor, in Combination with Carboplatin, Effectively Inhibit Ovarian Cancer Tumor Growth. (PubMed, Mol Cancer Ther) - "Initial results showed that omipalisib, verteporfin, CA3, mitoxantrone, navitoclax, venetoclax, and YM155 had significant single-drug activity in either the ALDHlo or both the ALDHlo/ALDHhi cell populations...In vivo, the combination of navitoclax/YM155/carboplatin decreased ovarian cancer metastasis, decreased the percentage of ALDHhi ovarian cancer cells in tumors, and increased survival when compared with carboplatin treatment alone in xenograft models. Our results suggest that the combination of navitoclax/YM155/carboplatin has promise as a therapy for treating ovarian cancer."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • CA3

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

Combined Omipalisib and MAPK Inhibition Suppress PDAC Growth. (PubMed, Cancers (Basel)) - "In vivo oral administration of combined Omipalisib/Trametinib treatment was significantly more effective than Omipalisib/SHP099 in reducing implanted tumor growth, and the Omipalisib/Trametinib treatment more effectively reduced tumor progression and prolonged survival in an aggressive genetically engineered mouse model of PDAC than either Omipalisib or Trametinib alone. Altogether, our data support a rationale for a dual treatment strategy targeting both PI3K and MAPK pathways in pancreatic cancers."

Journal • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • PIK3CA

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 2025 ➔ Mar 2026

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

Combined Omipalisib and MAPK Inhibition Suppress PDAC Growth (Multidisciplinary Digital Publishing Institute) - "In vivo oral administration of combined Omipalisib/Trametinib treatment was significantly more effective than Omipalisib/SHP099 in reducing implanted tumor growth, and the Omipalisib/Trametinib treatment more effectively reduced tumor progression and prolonged survival in an aggressive genetically engineered mouse model of PDAC than either Omipalisib or Trametinib alone."

Preclinical • Pancreatic Ductal Adenocarcinoma

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 2025 ➔ Mar 2026

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

A Novel 3D High-Throughput Phenotypic Drug Screening Pipeline to Identify Drugs with Repurposing Potential for the Treatment of Ovarian Cancer. (PubMed, Adv Healthc Mater) - "This approach has expedited the identification of promising candidates, such as rapamycin, which demonstrated limited activity as a monotherapy but synergized effectively with standard treatments like cisplatin and paclitaxel in vitro. In combination with platinum-based therapy, Rapamycin led to significant in vitro cytotoxicity and a marked reduction in tumor burden in a syngeneic in vivo model. This proof-of-concept study underscores the potential of drug repurposing to rapidly advance new treatments into clinical trials for OC, offering renewed hope for patients with advanced disease."

Journal • Oncology • Ovarian Cancer • Solid Tumor

InfoScan: A New Transcript Identification Tool Based on scRNA-Seq and Its Application in Glioblastoma. (PubMed, Int J Mol Sci) - "Drug sensitivity assays indicated that neoplastic-stemness cells might be sensitive to omipalisib, a PI3K inhibitor, pointing to a potential therapeutic target. InfoScan offers a robust framework for exploring complex transcriptomic landscapes and characterizing rare cell populations, providing valuable insights into GBM biology and advancing precision cancer therapy."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • SPP1

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 2025 ➔ Jan 2026

Trial completion date • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Follicular Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF • EGF • HER-2 • HRAS • KRAS • NRAS

Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Dec 2024

Trial completion • Trial completion date • Colorectal Cancer • Hepatocellular Cancer • Hepatology • Liver Failure • Oncology • Solid Tumor • BRAF

An mTOR inhibitor discovery system using drug-sensitized yeast. (PubMed, Geroscience) - "Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species...In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identify TOR1-dependent growth inhibition in the drug-sensitized background...Additionally, for the TOR inhibitor AZD8055, the drug-sensitive system resolves that the compound results in TOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wild-type yeast strain background. Our platform also identifies the caffeine analog aminophylline as a TOR1-dependent growth inhibitor via selective tor1 growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine and found no evidence for TOR inhibition using our yeast growth-based model. Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR..."

Journal • Oncology

PI3K/mTOR dual inhibitor GSK458 and arsenic trioxide exert synergistic anti-tumor effects against ovarian clear cell carcinoma. (PubMed, Mol Cancer Ther) - "Mutations in the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase (PI3K/AKT/mTOR) pathway are frequently reported in OCCC. Compared to any monotherapy, the combination treatment significantly suppressed tumor growth in vivo, thereby enhancing survival. Overall, our findings highlight the potential of the novel combination of GSK458 and arsenic trioxide combination for OCCC treatment."

Journal • Clear Cell Carcinoma • Oncology • Ovarian Cancer

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 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

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