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

Exclusion Criteria

• •* 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.
• •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.