obrindatamab (MGD009) / MacroGenics - LARVOL DELTA

Molecular Imaging of B7-H3-Targeting Bispecific T Cell-Engaging Antibody MGD009 in Glioblastoma Models. (PubMed, ACS Appl Mater Interfaces) - "In orthotopic U-87MG models, tumor uptake of 89Zr-labeled MGD009 reached 18.10 ± 0.87% ID/g at 24 h p.i. Additionally, the liver, spleen, and bone marrow also showed a relatively high radioactivity. These findings provide critical insights into the biodistribution and tumor-targeting of MGD009, supporting its potential clinical application in glioblastoma treatment."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CD276

High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors suggesting potential anti-B7-H3 therapy in triple-negative breast cancer (SABCS 2023) - "Multiple anti-B7-H3 therapies has been raised, such as DS-7300, MGA271, MGD009, and B7-H3 chimeric antigen receptor T-cell immunotherapy (CAR-T)...In the durvalumab-dependent cohort, paclitaxel-dependent cohort, anthracycline-dependent cohort, and our recruited NAT cohort, the B7-H3highPDL1low subgroup exhibited the lowest therapeutic response. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression that could potentially be applied to predict the therapeutic responses in TNBC, and suggests a potential biomarker-guided anti-B7-H3 therapy. Based on the classifier, we can select potential beneficiaries to deliver personalized medical services."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD276 • CD8 • PD-L1

B7-H3/CD276 Inhibitors: Is There Room for the Treatment of Metastatic Non-Small Cell Lung Cancer? (PubMed, Int J Mol Sci) - "In addition to its role in immune modulation, B7-H3 also promotes pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism. In this review, we will provide an overview of this newly characterized immune checkpoint molecule and its development in the management of metastatic NSCLC."

IO biomarker • Journal • Metastases • Review • Immune Modulation • Immunology • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD276 • PD-1 • PD-L1

MGD009/MGA012 Combination in Relapsed/Refractory Cancer (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: MacroGenics | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Oncology • Prostate Cancer • Solid Tumor • CD276

MGD009/MGA012 Combination in Relapsed/Refractory Cancer (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: MacroGenics | Trial completion date: Dec 2021 ➔ Jun 2022 | Trial primary completion date: Dec 2021 ➔ Jun 2022

Combination therapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • CD276

A phase 1, open label, dose escalation study of MGD009, a B7-H3 x CD3 DART® protein, in combination with MGA012, an anti-PD-1 antibody, in patients with relapsed or refractory B7-H3- expressing tumors (SITC 2018) - P1; "Expansion cohorts will be limited to 6 tumor types (N=20/cohort) treated at the MTD/MAD of the combination. The study is ongoing at approximately 6 U.S. centers."

Clinical • Combination therapy • IO biomarker • P1 data • PD(L)-1 Biomarker • Oncology • Solid Tumor

[VIRTUAL] A phase I/II, two-part, multicenter, first-in-human study of DS-7300a in patients with advanced solid malignant tumors. (ASCO 2020) - P1/2 | "Key exclusion criteria include prior treatment with orlotamab, enoblituzumab, other B7-H3–targeted agents, or an antibody-drug conjugate that is conjugated with a topoisomerase I inhibitor. This trial is currently in the dose-escalation part. Research Funding: Daiichi Sankyo Co., Ltd."

Clinical • P1/2 data • Head and Neck Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A phase 1, open label, dose escalation study of MGD009, a humanized B7-H3 x CD3 DART protein, in combination with MGA012, an anti-PD-1 antibody, in patients with relapsed or refractory B7-H3-expressing tumors. (ASCO 2018) - P1; "Dose escalation uses a 3+3+3 design, with patients treated every 2 weeks with escalating doses of IV MGD009 (starting dose 3g/kg) and MGA012 at a dose of 3mg/kg in all cohorts. Cohort expansions will be limited to 6 tumor types (N = 20/cohort) treated at the maximum tolerated dose of the combination."

Clinical • Combination therapy • IO biomarker • P1 data • PD(L)-1 Biomarker • Solid Tumor

MGD009/MGA012 Combination in Relapsed/Refractory Cancer (clinicaltrials.gov) - P1; N=25; Active, not recruiting; Sponsor: MacroGenics; Trial completion date: Dec 2022 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • CD276

Safety Study of MGD009 in B7-H3-expressing Tumors (clinicaltrials.gov) - P1; N=114; Recruiting; Sponsor: MacroGenics

Clinical • New P1 trial • P1 data • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • Urothelial Cancer • CD276

Safety Study of MGD009 in B7-H3-expressing Tumors (clinicaltrials.gov) - P1; N=67; Terminated; Sponsor: MacroGenics; N=200 ➔ 67; Trial completion date: Mar 2020 ➔ Nov 2019; Active, not recruiting ➔ Terminated; Business decision (not for safety reasons)

Clinical • Enrollment change • Trial completion date • Trial termination • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • CD276

Safety Study of MGD009 in B7-H3-expressing Tumors (clinicaltrials.gov) - P1; N=59; Active, not recruiting; Sponsor: MacroGenics; Recruiting ➔ Active, not recruiting; N=114 ➔ 59

Clinical • Enrollment change • Enrollment closed • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • CD276

Safety Study of MGD009 in B7-H3-expressing Tumors (clinicaltrials.gov) - P1; N=200; Active, not recruiting; Sponsor: MacroGenics; N=59 ➔ 200; Trial completion date: Dec 2020 ➔ Mar 2020; Trial primary completion date: Dec 2018 ➔ Dec 2019

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • CD276

[VIRTUAL] Targeting B7-H3 with Multiple Therapeutic Modalities (PEGS 2020) - "We have developed an Fc-enhanced mAb (enoblituzumab), CD3 bispecific DART® molecule (MGD009) and ADC (MGC018) to target NK cells, T cells, or direct a cytotoxic payload to B7-H3. The strategic rationale and development update will be presented."

Oncology • CD276

MGD009/MGA012 Combination in Relapsed/Refractory Cancer (clinicaltrials.gov) - P1; N=25; Active, not recruiting; Sponsor: MacroGenics; Recruiting ➔ Active, not recruiting; N=139 ➔ 25

Clinical • Combination therapy • Enrollment change • Enrollment closed • Oncology • Prostate Cancer • Solid Tumor

MGD009/MGA012 Combination in Relapsed/Refractory Cancer (clinicaltrials.gov) - P1; N=13; Active, not recruiting; Sponsor: MacroGenics; Recruiting ➔ Active, not recruiting; N=165 ➔ 13

Clinical • Combination therapy • Enrollment change • Enrollment closed

MGD009/MGA012 Combination in Relapsed/Refractory Cancer (clinicaltrials.gov) - P1; N=139; Recruiting; Sponsor: MacroGenics; Active, not recruiting ➔ Recruiting; N=13 ➔ 139

Clinical • Combination therapy • Enrollment change • Enrollment open

Selection of a bispecific trivalent HER2 x CD137 TRIDENT format providing optimal tumor-anchored immune co-stimulation (AACR 2019) - "...Here we evaluate a panel of Fc-bearing HER2 x CD137 bispecific molecules incorporating different valency and geometry to define the format providing optimal CD137 co-stimulation in a tumor-cell anchor-dependent manner. An anti-HER2 mAb specificity that does not cross compete with margetuximab, trastuzumab or pertuzumab and a proprietary anti-CD137 mAb were utilized to assemble a set of HER2 x CD137 bispecific molecules in bivalent and tetravalent DART® or trivalent TRIDENTTM configurations...Similarly, HER2 x CD137 bispecific molecules enhanced the in vitro activity of orlotamab, a B7-H3 x CD3 bispecific DART molecule that up-regulates CD137 during T-cell redirected killing... An optimal HER2 x CD137 bispecific format providing maximal CD137 activation in a HER2- dependent manner was identified as a trivalent TRIDENT molecule bearing bivalent CD137 and monovalent HER2 binding. Combinatorial activity with HER2 x CD137 bispecifics was observed with both a..."

IO Biomarker

"#MacroGenics Announces Removal of #PartialClinicalHold on #MGD009 Program by #FDA $MGNX https://t.co/1HzGj0shwL" (@1stOncology)

MacroGenics announces removal of partial clinical hold on MGD009 program by FDA (GlobeNewswire) - "MacroGenics...announced that the...FDA has lifted the partial clinical hold on its Phase 1 monotherapy and combination studies of MGD009, a B7-H3 × CD3 bispecific DART® molecule. Enrollment of new patients in the U.S. has been cleared to proceed with these trials...During the partial clinical hold, previously enrolled study participants were allowed to continue to receive drug at their pre-assigned dose."

Enrollment status • FDA event