GDC-0623 / Roche - LARVOL DELTA

Myeloma-Developing Regimens Using Genomics (MyDRUG) (clinicaltrials.gov) - P1/2 | N=103 | Completed | Sponsor: Multiple Myeloma Research Consortium | Recruiting ➔ Completed | N=228 ➔ 103 | Trial completion date: Feb 2024 ➔ Dec 2024 | Trial primary completion date: Feb 2022 ➔ Dec 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • BRAF • SLC1A5

An in vitro pharmacogenomic approach reveals subtype-specific therapeutic vulnerabilities in atypical teratoid/rhabdoid tumors (AT/RT). (PubMed, Pharmacol Res) - "Subtype-dependent drug response profiles demonstrated sensitivity of AT/RT-SHH cell lines to B-cell lymphoma 2 (BCL2) and heat shock protein 90 (HSP90) inhibitors, and increased activity of microtubule inhibitors, kinesin spindle protein (KSP) inhibitors, and the eukaryotic translation initiation factor 4E (eIF4E) inhibitor briciclib in a subset of AT/RT-MYC cell lines. In summary, our in vitro pharmacogenomic approach revealed preclinical evidence of tumor type- and subtype-specific therapeutic vulnerabilities in AT/RT cell lines that may inform future in vivo and clinical evaluations of novel pharmacological strategies."

IO biomarker • Journal • Preclinical • B Cell Lymphoma • Brain Cancer • CNS Tumor • Embryonal Tumor • Glioma • Lymphoma • Malignant Glioma • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • BCL2 • CDC37 • EIF4E • HSP90AA1 • SMARCA4 • SMARCB1

High in vitro and in vivo activity of BI-847325, a dual MEK/Aurora kinase inhibitor, in human solid and hematologic cancer models. (PubMed, Cancer Res Commun) - "BI-847325 showed a broader range of activity than the MEK inhibitor GDC-0623. In conclusion, dual MEK/Aurora kinase inhibition shows remarkable potential for treating multiple types of hematological and solid tumors. The combination with capecitabine was synergistic in colorectal, gastric, and mammary cancer."

Journal • Preclinical • Acute Lymphocytic Leukemia • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • MAP2K1 • NRAS

Myeloma-Developing Regimens Using Genomics (MyDRUG) (clinicaltrials.gov) - P1/2; N=228; Recruiting; Sponsor: Multiple Myeloma Research Consortium; Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways. (PubMed, Int J Endocrinol) - "However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation."

Journal • CCND1 • IL1B • MMP13 • MMP9 • PCNA

A study evaluating the safety, tolerability, and pharmacokinetics of GDC-0623 in patients with locally advanced or metastatic solid tumors (clinicaltrials.gov) - P1, N=61; Sponsor: Genentech; Active, not recruiting; Primary trial completion date: Dec 2013 -> May 2014. 

Trial primary completion • Oncology

Lignin-graft-PLGA drug-delivery system improves efficacy of MEK1/2 inhibitor in triple-negative breast cancer cell line. (PubMed, Nanomedicine (Lond)) - "We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro."

Journal • Preclinical

Novel lignin-conjugated PLGA drug delivery system improves efficacy of MEK1/2 inhibitor in triple negative breast cancer (AACR-NCI-EORTC 2019) - "L-PLGA-GDC was more effective at reversing EMT than free GDC-0623 and PLGA-GDC NPs. Our findings indicate that lignin conjugation improves characteristics of PLGA NPDDSs and improves efficacy of GDC-0623 in multiple assays."

Clinical

Strong anti-tumor activity of MEK inhibitor GDC-0623 and determination of predictive biomarkers (AACR 2019) - "Integrative analysis with significant genomic and transcriptomic parameters is currently ongoing to develop a molecular predictor of response to GDC-0623. Extending evaluation of the compound in vivo and validating predictors of response are needed to complete these preclinical investigations."

Biomarker