efgivanermin alfa (MEDI1873) / AstraZeneca - LARVOL DELTA

MEDI1873, a GITR ligand fusion protein (GITRL FP), induces effector T-cell proliferation, modulates T-regulatory cell function and has the potential to combine with checkpoint inhibitors (AACR 2017) - P1; "Combinations of immunotherapies are generating exciting results in the clinic, therefore, we sought to assess the potential for GITRL FPs to combine with antibodies targeting either anti-PD-L1 (durvalumab) or anti-CTLA-4 (tremelimumab) using both in vitro and in vivo systems. Overall, our data suggest that therapeutically targeting GITR with a multimeric fusion protein, GITRL FP, may provide increased agonistic potential versus an antibody, and have the ability to both activate effector T-cells and modulate Tregs through suppression and/or depletion. Finally, combination studies provide preclinical evidence to support the rationale for combination of MEDI1873 with anti-PD-L1 or anti-CTLA-4 antibodies further reinforcing the potential of targeting the GITR pathway as a therapeutic approach to treating patients with cancer."

Checkpoint inhibition • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Pharmacodynamic activity of MEDI1873, a Glucocorticoid-Induced tumor necrosis factor family-related protein (GITR) agonist molecule, administered intravenously to patients with advanced solid tumors (SITC 2018) - P1; "Conclusions MEDI1873 engages GITR on circulating blood cells resulting in increased peripheral IFNγ production and CD4+ memory T-cell proliferation coupled with a decrease in intratumoral GITR+/FOXP3+ cells. These pharmacodynamic effects are consistent with the compound’s mechanism of action and may be enhanced in patients with high baseline GITR Expression."

Clinical • IO biomarker • PD(L)-1 Biomarker • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

A Phase 1 study of MEDI1873, a novel GITR agonist, in advanced solid tumors (ESMO 2018) - P1; "MEDI1873 has an acceptable safety profile in heavily pretreated pts with solid tumors. PD changes in blood and tumor coupled with prolonged SD in several pts support further clinical exploration of doses ≥250 mg."

P1 data • Colorectal Cancer • Head and Neck Cancer • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer

Novel PD-1/GITRL bispecific fusion protein delivering concurrent T cell co-stimulation and checkpoint pathway inhibition (AACR 2018) - "...Furthermore, the PD-1/GITRL FP bispecific constructs elicit T-cell responses in vitro that are at least equivalent to a combination of a) the parental molecules and b) MEDI1873 (a GITR agonist currently undergoing clinical evaluation) and an PD-1 mAb...These data demonstrate that the antitumor activity for these novel molecules is equivalent to the combination of GITRL-FP and PD-1 mAb in the B16 model. In summary, the simultaneous dual targeting of PD-1 and GITR pathways mediated by these two novel bispecific molecules induces robust T-cell activity that is at least equivalent to a combination of molecules targeting these pathways, thereby demonstrating strong potential as a novel anticancer therapy."

Oncology

"#OnlineFirst: MEDI1873, an agonistic IgG1 fusion protein targeting GITR, has an acceptable safety profile but further development is not planned due to lack of #TumorResponse. @AnaingMD @pharmanach @DrCrystalD https://t.co/wNFMpOVdTY" (@CCR_AACR)

Clinical • Oncology

Safety and Clinical Activity of MEDI1873, a Novel GITR Agonist, in Advanced Solid Tumors. (PubMed, Clin Cancer Res) - "MEDI1873 showed acceptable safety up to 500 mg IV Q2W with pharmacodynamic activity, and prolonged SD in some patients. However, further development is not planned due to lack of demonstrated tumor response."

Clinical • Journal • Cardiovascular • Myocardial Infarction • Pain • Solid Tumor

MEDI1873: Data from P1 trial (NCT02583165) for advanced solid tumors in 2019 (AstraZeneca) - Q2 FY 2017 Results

P1 data • Oncology

MEDI1873: Data from P1 trial (NCT02583165) for advanced solid tumors in 2020 or later (AstraZeneca) - Q3 2018 Results

P1 data • Oncology • Solid Tumor

A Study in Adult Subjects With Select Advanced Solid Tumors (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • IO Biomarker • Trial completion