A Dose Escalation and Expansion Study of TRX518 in Combination With Cyclophosphamide Plus Avelumab in Advanced Solid Tumors

Inclusion Criteria: * Advanced Solid Malignancies in Dose Escalation Parts 1 and 2: * Histologically documented metastatic or locally advanced, incurable solid malignancy. * At least one prior line of systemic therapy for metastatic or locally advanced disease. * Advanced Triple Negative Breast Cancer (Dose Expansion): * Histologically proven invasive breast carcinoma with triple-negative receptor status. * At least 1 but no more than 2 prior lines of chemotherapy for metastatic or locally advanced disease. * Advanced Hormone Receptor-Positive/Endocrine-Refractory Breast Cancer (Dose Expansion): * Histologically proven invasive breast carcinoma with hormone receptor+, HER2- status. * Only postmenopausal women are eligible. - Previously received at least 1 line of aromatase inhibitor ± cyclin dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Prior combination therapies of AI or selective estrogen receptor degrader (SERD \[fulvestrant\]) ± CDK 4/6 inhibitor or AI plus everolimus will be permitted. Up to 1 prior line of systemic chemotherapy for metastatic disease is allowed. * Advanced Metastatic Castration-Resistant Prostate Cancer (Dose Expansion): * Histologically or cytologically confirmed prostate adenocarcinoma or poorly differentiated carcinoma of the prostate. * Surgically or medically castrated, with testosterone levels of \< 50 ng/dL (\< 2.0 nM). If a patient is being treated with LHRH agonists, this therapy must have been initiated at least 4 weeks prior to treatment start and must be continued throughout the study. * Patients must have received ≥1 androgen receptor (AR) signaling inhibitors and had disease progression RECIST v1.1 after no more than 1 prior chemotherapy for mCRPC. * Advanced Platinum-Resistant Ovarian Cancer (Dose Expansion): * Histologically or cytologically confirmed diagnosis of metastatic, advanced, or recurrent platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer. * Platinum-resistant ovarian cancer defined as disease progression following a response within 180 days following the last administered dose of platinum therapy. Patients who have lack of response (SD) or disease progression while receiving the most recent platinum-based therapy are not eligible. * Received up to 3 lines of systemic therapy for platinum-sensitive disease, with the most recent regimen platinum-containing, and no prior systemic therapy for platinum-resistant or refractory disease. * General: * Tumor tissue for mandatory pre-treatment and on-treatment biopsies. * One or more tumors measurable on radiographic imaging defined by RECIST 1.1. * Adult patients ≥18 years of age. * ECOG performance status (PS) score of 0 or 1. * Life expectancy of at least 12 weeks. * Disease-free of active second/secondary or prior malignancies for ≥2 years, with the exception of currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix or breast. * Acceptable liver, renal, hematologic and coagulation function. Exclusion Criteria: * Hematologic malignancies or multiple myeloma. * For the Dose Expansion cohorts the following cancers are not permitted: * Any of the following pure histologies of ovarian cancer: germ cell, sex cord stroma, carcinosarcoma, or sarcoma. * Small cell or pure neuroendocrine prostate carcinoma that has not yet been treated with at least one line of platinum-based chemotherapy (prostate adenocarcinoma with immunohistochemical neuroendocrine differentiation but without histological small cell that is naïve to platinum-based chemotherapy will be allowed.) * Inflammatory breast cancer. * New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia. * Cardiac function: * Known ejection fraction of \<50% by gated radionuclide study (e.g., multi-gated acquisition scan); * Fridericia-corrected QT interval (QTcF) \>470 msec (female) or \>450 msec (male), or history of congenital long QT syndrome; * Any ECG abnormality, including pericarditis, that in the Investigator's opinion, would preclude safe participation in the study. * Active, uncontrolled bacterial, viral, or fungal infections within 7 days of study entry requiring systemic therapy. * Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Known clinically important respiratory impairment. * History of (non-infectious) pneumonitis that required steroids or current pneumonitis. * History of interstitial lung disease. * Clinically significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis. * Known to be human immunodeficiency virus (HIV) positive or have hepatitis B surface antigen (HBSAg) or hepatitis C antibodies (HCAb) unless hepatitis C virus (HCV) RNA is undetected/negative. * History of major organ transplant (i.e., heart, lungs, liver, and kidney). * History of an allogeneic bone marrow transplant. * History of an autologous bone marrow transplant within 90 days of study entry. * Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible, provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Radiation must have been completed at least 14 days prior to study entry. Screening of asymptomatic patients without a history of CNS metastases is not required. * Serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor. * Pregnant or nursing women.