IRENE Study: Phase 2 Study of INCMGA00012 and the Oncolytic Virus Pelareorep in Metastatic Triple Negative Breast Cancer
This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012 and pelareorep and to see how well they work in treating patients with triple negative breast cancer that has spread to other parts of the body (metastatic). INCMGA00012 is a monoclonal antibody that works by attaching to the programmed cell death protein 1 (PD-1) and blocking this pathway, allowing the immune system to recognize and attack the cancer cells. Pelareorep is a type of virus called reovirus which occurs naturally and may break down cancer cells. Giving INCMGA00012 and pelareorep may slow the growth and spread of the cancer to another part of the body.
• Metastatic or inoperable locally advanced, histologically documented triple negative breast cancer (TNBC) (negative expression of estrogen receptor \[ER\], progesterone receptor \[PR\] and human epidermal growth factor receptor 2 \[HER2\] immunohistochemistry \[IHC\] 0 or 1+, HER2 fluorescence in situ hybridization \[FISH\] negative if IHC 2+, per American Society of Clinical Oncology \[ASCO\] College of American Pathologists \[CAP\] guidelines)
• Pre-menopausal and post-menopausal women who have received 1-2 prior lines of systemic therapy for metastatic triple negative breast cancer. Patients must have received at least one prior line of chemotherapy
• Patients who have received adjuvant therapy for locally advanced triple negative breast cancer may be eligible for the study if they relapse with metastatic disease within 6 months since completion of neo-adjuvant/adjuvant systemic therapy. The adjuvant/neoadjuvant therapy will be considered as 1 line of therapy
• Availability of tumor specimen for determination of PD-L1 and additional biomarker studies. Patient should be willing to undergo a pre-treatment biopsy as well as a biopsy after cycle 2 to evaluate the tumor microenvironment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients who have received prior treatment with anti-PD-1 or anti-PD-L1 inhibitors are eligible for the study
• Absolute neutrophil count \>= 1,000/uL
• Platelet count \>= 100,000/uL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin =\< 2 x upper limit of normal (ULN) or =\< 3 x ULN for subjects with Gilbert's disease or liver metastases
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (=\< 5 x ULN if evidence of hepatic involvement by malignant disease)
• Estimated glomerular filtration rate (eGFR) \>= 40 mL/min/1.73m\^2
• Lactate dehydrogenase (LDH) \< 2 x ULN
• Provision of signed and dated informed consent form
• Life expectancy \>= 3 months, as determined by the investigator
• Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be uni-dimensionally measurable as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to initiation of study treatment
• Subjects with central nervous system (CNS) metastases treated with radiation therapy (whole-brain radiation therapy \[WBXRT\] or stereotactic radiosurgery \[SRS\]) are eligible if, \> 28 days following completion of radiation therapy (XRT), they show stable disease on post-treatment magnetic resonance imaging (MRI)/computed tomography (CT), are off corticosteroids, and are neurologically stable
• Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti estrogens, or ovarian suppression
‣ Patients who are not postmenopausal (\>= 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within 14 days of treatment initiation
⁃ Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 12 weeks after their last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner