MGD007 / MacroGenics - LARVOL DELTA

MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b/2; N=38; Completed; Sponsor: MacroGenics; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-1 • PD-L1

A phase 1 study of MGD007, a humanized gpA33 x CD3 DART® protein, in combination with MGA012, an anti-PD-1 antibody, in patients with relapsed/refractory metastatic colorectal cancer (SITC 2018) - P1b/2; "Patients are eligible irrespective of KRAS/MMR status, after treatment with 2-5 prior standard therapy regimens in the metastatic setting, or if they did not tolerate fluoropyrimidines, oxaliplatin or irinotecan chemotherapy or are not good candidates for standard of care. Patients may be treated for up to 12 cycles in the absence of disease progression, DLT, or other criteria for permanent discontinuation. Enrollment is ongoing."

Clinical • Combination therapy • IO biomarker • P1 data • PD(L)-1 Biomarker • Colorectal Cancer

Recent Advances on Immune Targeted Therapy of Colorectal Cancer Using bi-Specific Antibodies and Therapeutic Vaccines. (PubMed, Biol Proced Online) - "For this aim, all data were extracted from Google Scholar, PubMed, Scopus, and Elsevier, using keywords cancer vaccines; CRC immunotherapy and CRC mRNA vaccines. About 97 articles were selected and investigated completely based on the latest developments and novelties on bi-specific antibodies, mRNA vaccines, nanobodies, and MGD007."

Journal • Review • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Immunotherapy of colorectal cancer by the T-cell targeted DART protein MGD007: Cellular mechanisms of action (AACR 2018) - "Here we further characterize MGD007 cellular mechanisms associated with redirected T-cell killing, cytokine responses and modulation with steroids.MethodRedirected killing assays were performed using luciferase labelled gpA33+ve Colo205 or RECA0201-GF colorectal cancer stem-like cells (CSLC) with freshly isolated PBMC or fractionated T-cell populations; Treg cells (CD4+, CD127lo, CD25+) were expanded for 14 days in presence of IL-2 and rapamycin and confirmed to be suppressive; steroids (budesonide and dexamethasone) were evaluated at pharmacologically relevant concentrations; multi-parameter FACS and ELISA were performed to determine cell surface marker expression and cytokine levels respectively.ResultsMGD007 displays potent redirected T-cell killing of gpA33+ve CRC cells, including complete lysis of CRC stem cell-like models. Biological activity modulation is also feasible through induction of cytolytic Tmem cells with diminished cytokine release p

IO Biomarker • Colorectal Cancer

MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b/2; N=52; Recruiting; Sponsor: MacroGenics; N=104 ➔ 52

Clinical • Combination therapy • Enrollment change

MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b/2; N=52; Active, not recruiting; Sponsor: MacroGenics; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed

Product discontinued (GlobeNewswire) - CRC, Oncology

Development of MGD007, a gpA33 x CD3 bispecific DART® protein for T-cell immunotherapy of metastatic colorectal cancer. (PubMed, Mol Cancer Ther) - "In cynomolgus monkeys, 4 weekly doses of 100 µg/kg were well tolerated, with prolonged PK consistent with that of an Fc-containing molecule. Taken together MGD007 displays potent activity against colorectal cancer cells consistent with a mechanism of action endowed in its design and support further investigation of MGD007 as a potential novel therapeutic treatment for colorectal cancer."

IO Biomarker • Journal • PD(L)-1 Biomarker

MacroGenics provides update on corporate progress and second quarter 2019 financial results (Macrogenics Press Release) - "MacroGenics recently met with FDA to discuss its plans regarding a Phase 2/3 registration-directed study of enoblituzumab in combination with MGA012 in patients with squamous cell carcinoma of the head and neck (SCCHN) and anticipates initiating the trial in the fourth quarter of 2019....MGD013 Dose Expansion: MacroGenics has enrolled approximately 100 patients in the Phase 1 dose expansion study in up to nine tumor types and expects to submit data from this monotherapy trial for presentation at a scientific conference in the second half of 2019. MGD007: The Company expects to provide a clinical update regarding this study in the first quarter of 2020."

Enrollment status • New P2/3 trial • P1 data