MC# 21-20 - A Phase I/IIa Open-Label Dose Escalation and Dose Expansion Study of T3011 when Administered via Intravenous Infusion as a Single Agent and in Combination with Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors
Disease Type(s): Solid Tumor
Phase(s): I, II
Drug Classification(s): Viral Therapy
Molecular Target(s): n/a
Mechanism of Action
T3011 is a genetically modified, attenuated oncolytic herpes simplex virus that produces IL-12 and FAB fragment of Anti-PD1 Antibody.
In this study, the sponsor and investigators want to learn:
- About the safety and tolerability of T3011 alone or in combination with pembrolizumab
- How proteins that indicate the status of your disease are affected with use of T3011
- If T3011 prevents or delays tumor growth or shrinks existing tumors
- How quickly T3011 is removed from the blood
- Participants with one of the following cancers:
- Pathologically confirmed, locally recurrent or metastatic solid tumors (Phase 1 Part A and B)
- Histologically or cytologically confirmed NSCLC that is recurrent or metastatic (Phase 2a)
- Histologically or cytologically diagnosed advanced solid tumors with metastasis in liver and/or lung (Phase 2a)
- Disease progression after standard of care (SOC) therapy or in the opinion of the Investigator unlikely to benefit from SOC therapy. SOC may include, but is not limited to, prior chemotherapy, targeted therapy or immunotherapy.
- Age 18 years or older
- Measurable disease per RECIST version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status 0 – 1
- Life expectancy > 12 weeks
- Adequate bone marrow function defined by absolute neutrophil count (ANC) of ≥ 1.5 × 109/L, platelet count of ≥ 100 × 109/L, and hemoglobin of ≥ 8.5 g/dL
- Adequate hepatic function defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN) and total bilirubin ≤ 1.5 × ULN (except patients with Gilbert’s Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Adequate renal function defined as creatinine clearance > 50 mL/min as determined by the Cockcroft-Gault equation
- Female participants must be surgically sterile (or have a monogamous partner who is surgically sterile), or be at least 2 years postmenopausal, or commit to using 2 acceptable forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 6 months following the last dose of study treatment. Male participants must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 6 months following the last dose of study treatment.
- Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening within 14 days of dosing with T3011 and a negative urine pregnancy test pre-dose on C1D1
- Last dose of previous anticancer therapy ≥ 21 days; radiotherapy > 21 days (except prior focal palliative radiotherapy must have been completed at least 1 week prior to the first dose of study treatment); major surgery > 21 days; or last dose of therapy with tyrosine kinase inhibitors within 5 times the half-life of the inhibitor prior to first dose of study treatment. Last dose of checkpoint inhibitor ≥ 14 days, as long as treatment related toxicities resolve to ≤ Grade 1.
- Resolution of all prior anticancer therapy toxicities (except for alopecia) to ≤ Grade 1. Note: patients previously treated with immunotherapy who have endocrinopathies may enroll if on adequate replacement therapy. Patients with toxicities attributed to systemic prior anticancer therapy, which are not expected to resolve and result in long lasting sequelae, such as neuropathy or ototoxicity after platinum-based therapy, are permitted to enroll.
- Willingness to provide pre- and post-treatment fresh tumor biopsy specimens, if tumor is easily accessible, as specified in the Schedule of Assessments. Participant may be eligible to participate without providing fresh tumor biopsy specimens, following discussion with and approval from the Medical Monitor.
- Capable of understanding and complying with protocol requirements
- Signed and dated institutional review board/independent ethics committee (IRB/IEC) approved informed consent form (ICF) before any protocol-directed screening procedures are performed
- Prior treatment with another oncolytic virus (OV) or cellular therapy
- Previous unacceptable intolerance to anti-PD-1 monoclonal antibody
- Requires continued concurrent systemic therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir). Topical use of drugs against HSV are allowed.
- Live vaccines within 4 weeks of initiation of study treatment. (Seasonal flu or SARS-CoV-2 vaccines that do not contain live viruses are permitted.)
- Primary or acquired immunodeficient states (leukemia, lymphoma, human immunodeficiency virus [HIV]/AIDS)
- Pregnant or lactating
- Splenectomy, previous allogenic tissue/solid organ transplant
- Active hepatitis B virus, hepatitis C virus, or a positive serological test at Screening
- Patients who test positive for anti-HCV Ab but negative for HCV ribonucleic acid (RNA) are considered eligible to participate in the study
- Patients who are HBsAg+ and/or HBcAb+ and have a DNA load < 2000 IU/mL (104 copies/mL) are considered eligible to participate in the study
- Active autoimmune disease or other medical conditions (e.g., active interstitial lung disease/pneumonitis or eczema, psoriasis, or other clinically significant dermatologic disorders) requiring chronic systemic steroid (> 10 mg/day prednisone or equivalent) or immunosuppressive therapy within 6 months prior to first administration of study treatment (unless agreed otherwise between the Medical Monitor and the Investigator on a case-by-case basis). Non-systemic corticosteroids (eg, topical, inhaled) are allowed.
- Patients with untreated and/or symptomatic metastatic central nervous system (CNS) disease. However, patients with brain/CNS metastases who have undergone surgery or radiotherapy, whose disease is stable and who have been on a stable dose of corticosteroids (≤ 10 mg prednisone or equivalent) for at least 4 weeks prior to the first administration of study treatment will be eligible.
- History of seizure disorders within 6 months of Screening
- Active oral or skin herpes lesion at Screening
- Congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest), or clinically significant cardiac arrhythmias
- History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody or their excipients
- Known or suspected active infection with SARS-CoV-2 virus
- Other systemic conditions or organ abnormalities that, in the opinion of the Investigator, may interfere with the conduct and/or interpretation of the current study
- Dallas, TX - Mary Crowley Cancer Research - Medical City