A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms
Advanced Solid Tumors, Hematologic Neoplasms, Ovarian Cancer
About this trial
This is an interventional treatment trial for Advanced Solid Tumors
Eligibility Criteria
Inclusion Criteria:
- Histologically proven, locally advanced unresectable or metastatic solid tumors (or hematologic malignancies, Cohort Expansion only) for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy ≥ 12 weeks
- Measurable disease
- Tissue specimen available for retrospective analysis of PD-1, PD-L1, LAG-3, and MHC-II expression
- Acceptable laboratory parameters
HER2+ Cohort:
- Locally advanced or metastatic HER2+ locally advanced or metastatic solid tumors, regardless of organ of origin.
i. The cancer must have progressed following standard therapy, or has progressed during or after HER2-directed therapy if approved and available for patients with HER2+ breast, gastric, or gastroesophageal junction cancer.
ii. History of HER2 positivity defined as 3+ by IHC or 2+ by Immunohistochemistry (IHC) in combination with in situ hybridization (ISH) positivity most recent tumor biopsy.
- All patients in the HER2+ cohort must be willing to provide consent for a baseline and on-treatment tumor biopsy during the screening period and within 14 days prior to Cycle 3 Day 1. Exceptions may be made based on a medical contraindication at the discretion of the Sponsor's Medical Monitor. This requirement will be discontinued after an adequate number of samples are collected, as determined by the Sponsor.
Exclusion Criteria:
- Symptomatic central nervous system (CNS) metastases or primary CNS lymphoma
- History of allogeneic bone marrow, stem-cell, or solid organ transplant
- History of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
- Treatment with any systemic chemotherapy within 3 weeks prior to the initiation of study drug; treatment with biologics or investigational therapy within the 4 weeks prior to the initiation of study drug.
- Major surgery within 4 weeks prior to the initiation of study drug.
- Prior treatment with combination of monoclonal antibodies against PD-1 and LAG-3 (Cohort Expansion only).
- Treatment with radiation therapy within 2 weeks prior to the initiation of study drug.
- Clinically significant cardiovascular disease.
- QTcF prolongation > 480 milliseconds
- HER2+ cohort: left ventricular ejection fraction less than 50%
- Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
- Active pneumonitis or history of non-infectious pneumonitis.
- Clinically significant gastrointestinal disorders.
- Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.
- Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
- Known history of hepatitis B (except in hepatocellular carcinoma) or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR)
- Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed
- Dementia or altered mental status that would preclude understanding and rendering of informed consent
- Confirmed or presumed COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines/standards. Patients with a positive test result for SARS-CoV-2 infection, known asymptomatic infection, or presumed infection are excluded. Patients may be considered eligible after a resolved SARS-CoV-2 infection once he or she remains afebrile for at least 72 hours and after other SARS-CoV-2-related symptoms have fully recovered to baseline for a minimum of 72 hours.
Sites / Locations
- Banner MD Anderson Cancer Center
- USC/Norris Comprehensive Cancer Center
- UCLA Hematology & Oncology Clinic
- Hoag Memorial Hospital Presbyterian
- Florida Cancer Specialists & Research Institute
- University of Chicago Medicine
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Massachusetts General Hospital and Dana-Farber Cancer Institute
- Duke University Medical Center
- Cincinnati Children's Hospital Medical Center
- Stephenson Cancer Center, The University of Oklahoma
- University of Pennsylvania, Abramson Cancer Center
- UPMC Hillman Cancer Center
- Sarah Cannon Research Institute
- The University of Texas M.D. Anderson Cancer Center
- St Vincent's Hospital Sydney
- Calvary Mater Newcastle
- Southern Medical Day Care Centre
- Austin Health Melbourne
- "Complex Oncology Center - Burgas" EOOD
- "Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia
- Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia
- Prince of Wales Hospital
- Pratia MCM Kraków
- BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
- Med-Polonia Sp. z o.o.
- Vall d'Hebron Institute of Oncology
- Hospital Ruber Internacional
- START Madrid-CIOCC, Hospital HM Sanchinarro
- King Chulalongkorn Memorial Hospital
- Maharaj Nakorn Chiang Mai Hospital
- Songklanagarind Hospital
- Communal Nonprofit Enterprise "Cherkassy Regional Oncology Dispensary" of Cherkassy Regional Council
- Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinnytsia Regional Council
- Communal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
- Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council"
- Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"
- Communal Nonprofit Enterprise "Central City Clinical Hospital of Uzhhorod City Council", City Oncology Center, State Higher Educational Institution <<Uzhhorod National University>>
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Tebotelimab: 1 mg
Tebotelimab 3 mg
Tebotelimab: 10 mg
Tebotelimab: 30 mg
Tebotelimab: 120 mg
Tebotelimab: 400 mg
Tebotelimab: 600 mg
Tebotelimab: 800 mg
Tebotelimab: 1200 mg
Combination cohort 1
Combination Cohort 2
Monotherapy Cohort Expansion
Tebotelimab and margetuximab
Tebotelimab and margetuximab
Monotherapy expansion at 600 mg