Phase 1b Maintenance Therapy Study of ONT-10 in Patients With Solid Tumors

Open label Phase 1b maintenance therapy study to evaluate the long-term safety, immunogenicity, and anti-tumor effects of repeat-dose vaccination with ONT-10 in patients with previously treated Stage 3 or 4 solid tumors with histologies that have been associated with expression of the MUC1 antigen as described in the medical literature. Patients must have previously been enrolled on the Phase 1 clinical trial ONT-10-001, completed all treatment and follow-up through at least 12 weeks, experienced no dose limiting toxicity, and experienced no progression of disease per the immune-related Response Criteria. Patients will receive maintenance ONT-10 every 6 weeks.

Inclusion criteria

• Was enrolled on the Phase 1 clinical trial ONT-10-001 and:

• completed all treatment and follow-up through at least 12 weeks
• experienced no dose limiting toxicity (DLT)
• experienced no progression of disease per the irRC1
• Patients enrolling in the retreatment cohort may have experienced localized disease progression that was treated with definitive therapy to return the patient to a state of stable disease. Examples include localized disease progression treated with complete surgical resection, a solitary brain metastasis treated with complete surgical resection or curative intent stereotactic radiosurgery, or a solitary bone metastasis that is treated with curative-dose radiation therapy.
• Patients enrolling on the retreatment cohort must have locally and systemically stable disease following the definite local treatment.
• Last received ONT-10 a maximum of 6 months (unless approved by the medical monitor) prior to receiving the first dose of maintenance or retreatment cohort therapy
• ECOG 0 or 1
• Adequate baseline hematological parameters as defined by white blood cell count (WBC) ≥ 3.5 x 103/µL, lymphocyte count ≥ 1.0 x 103/µL, platelet count ≥ 100 x 103/µL, and hemoglobin ≥ 9 g/dL
• Adequate hepatic parameters as defined by total bilirubin ≤ 1.5 x upper limit of normal (ULN) and aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Resolution of all prior ONT-10 related toxicities to ≤ Grade 1in severity
• If female of child bearing potential, have a negative pregnancy test at screening
• If fertile male or female of child-bearing potential, agree to consistently use a highly effective method of birth control (including birth control pills, barrier device, or intrauterine device) from the time of consent through 3 months following the last dose of study drug
• Be able and willing to sign informed consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC)

Exclusion criteria

• Has medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
• Received treatment with any systemic chemotherapy, experimental agent, or radiation therapy (with the exception of palliative localized radiation therapy) following completion of treatment on the ONT-10-001 study
• Known history of autoimmune disease, arteritis, or vasculitis, including, but not limited to: lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), Grave's disease, Hashimoto's thyroiditis, Wegener's granulomatosis, temporal arteritis, and polyarteritis nodosa
• Has untreated or uncontrolled central nervous system (CNS) metastases, including patients who require glucocorticoid therapy for CNS metastases
• Known immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia; and/or other hereditary or congenital immunodeficiencies
• Chronic steroid or immunosuppressive therapy (except for low dose corticosteroids for chronic obstructive pulmonary disease [COPD] or topical steroids, which are allowed)
• Known to be positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Administration of any vaccine ≤ 4 weeks prior to first maintenance or retreatment cohort dose of ONT-10 with the exception of influenza, pneumococcus, and Tdap