Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors

Exclusion Criteria

• •Subjects who failed to show any response to initial treatment with PD-1/PD-L1 inhibitor (i.e. no Response or no Stable Disease).
• •Has active brain metastases or leptomeningeal disease. Subjects with asymptomatic CNS metastases which have been stable (defined as without evidence of progression by MRI for at least 28 days prior to initiation of therapy and any neurologic symptoms have returned to baseline) following treatment with surgery or radiation therapy are allowed.
• •Prior solid organ or hematologic transplant.
• •Treatment-related immune-mediated (or immune related) AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents, anti-CTLA4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were grade 3 or 4 in severity.
• •Subjects treated with chemotherapy, immunotherapy, biologic therapy, or other investigational agent within \<5 times the half-life of the agent or \<21 days (whichever is shorter) of starting study drug. Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.
• •Subjects treated with tyrosine kinase inhibitor therapy or completed palliative radiotherapy \<14 days from initiation of therapy.
• •Comorbidity requiring corticosteroid therapy (\>10mg prednisone/day or equivalent) within 7 days of starting experimental therapy. Physiologic replacement doses are allowed if they are ≤10mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
• •Significant cardiac dysfunction, New York Heart Association classification for chronic heart failure III-IV, symptomatic coronary artery disease, significant ventricular arrhythmias; myocardial infarction within 6 months; unstable, poorly controlled angina pectoris
• •Active, known or suspected autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs), except for replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.). Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in subjects with hypersensitivity to radiologic contrast agents are allowed
• •Has a serious active infection requiring systemic therapy
• •Subjects who have completed a course of antibiotics within the two weeks prior to dosing
• •Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the trial
• •Receipt of a live-virus vaccination within 28 days of planned treatment start
• •Known HIV infection, or active infection with hepatitis A, B or C
• •Has a history of (non-infectious) pneumonitis that required steroids or has current active pneumonitis
• •Known additional malignancy either progressing r requiring active treatment (except for non-melanoma skin cancer, in situ cervical cancer or prostate intraepithelial neoplasia) within the last 2 years
• •Female subjects who are breastfeeding
• •Known intolerance or hypersensitivity to study drugs
• •Subjects who are allergic to amoxicillin/clavulanic acid, erythromycin and imipenem
• •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• •Has a known inability for oral intake of capsules