| Eligibility |
Inclusion Criteria:
All subjects must meet the following criteria for inclusion:
1. Subjects with one of the following cancers:
• Pathologically confirmed, locally recurrent or metastatic solid tumors, including,
but not limited to NSCLC, hepatocellular carcinoma, colorectal cancer, ovarian cancer
and endometrial cancer (Phase 1).
2. Disease progression on or unlikely to respond to SOC therapy at the discretion of the
Investigator. SOC may include, but is not limited to, chemotherapy, targeted therapy
or immunotherapy.
3. Age 18 years or older.
4. At least one target lesion per RECIST version 1.1.
• A previously irradiated lesions can be considered as target lesion only if PD has
been unequivocally documented at that site since radiation.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
6. Life expectancy = 12 weeks.
7. Adequate bone marrow function defined by absolute neutrophil count (ANC) of = 1.5 ×
109/L, platelet count of = 100 × 109/L, and hemoglobin (Hb) of = 8.5 g/dL.
8. Adequate hepatic function defined as aspartate aminotransferase (AST)/alanine
aminotransferase (ALT) = 3 × upper limit of normal (ULN) and total bilirubin = 1.5 ×
ULN (except subjects with Gilbert's Syndrome, wherein total bilirubin < 3.0 mg/dL is
acceptable).
9. Adequate renal function defined as creatinine clearance > 50 mL/min as determined by
the Cockcroft-Gault equation.
10. Female subjects 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 subjects 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.
11. 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 (assessment not required at C1D1 if completed within the previous 7
days of C1D1).
Note: A woman is considered to be of childbearing potential if she is postmenarchal,
has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no
identified cause other than menopause), and is not permanently infertile due to
surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as
determined by the investigator (e.g., Müllerian agenesis).
12. Last dose of previous anticancer therapy = 21 days; radiotherapy > 14 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.
13. Resolution of all prior anticancer therapy toxicities (except for alopecia) to = CTCAE
version 5.0 Grade 1.
Note: subjects with immune-mediated endocrinopathies on replacement therapy are
eligible. Subjects with toxicities attributed to the prior anticancer therapy and not
expected to resolve, such as neuropathy or ototoxicity after platinum-based therapy,
are permitted to enroll. Subjects with other toxicities > CTCAE version 5.0 Grade 1
may be enrolled with approval from the sponsor.
14. Willingness to provide pre- and post-treatment fresh tumor biopsy specimens, if tumor
is easily accessible, as specified in the Schedule of Assessments. Subject is eligible
to participate without providing fresh tumor biopsy specimens, with approval from the
Medical Monitor.
15. Capable of understanding and complying with protocol requirements.
16. Signed and dated institutional review board/independent ethics committee (IRB/IEC)
approved informed consent form (ICF) before any protocol-directed screening procedures
are performed.
Exclusion Criteria:
Subjects are to be excluded from the study if they meet any of the following criteria:
1. Prior treatment with another OV (including T-VEC), tumor vaccines, cellular therapy or
gene therapy.
2. Prior treatment with anti-PD-(L)1 monoclonal antibody in combination with IL-12.
3. Subjects with rapidly disease progression, defined as subjects who cannot tolerate
interruption of systemic antitumor therapy for at least 8 weeks, according to the
investigator's judgment.
4. Previous intolerance to anti-PD-(L)1 monoclonal antibody or previous history of
immunotherapy induced non-infectious pneumonitis/interstitial lung disease.
5. Requires continued concurrent systemic therapy with any drug active against HSV
(acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet,
cidofovir). Topical use of drugs against HSV are allowed.
6. Live, attenuated vaccines within 4 weeks prior to initiation of study treatment
(subjects vaccinated with inactivated vaccines can be enrolled).
7. Primary or acquired immunodeficient states (leukemia, lymphoma, human immunodeficiency
virus [HIV]/acquired immunodeficiency syndrome [AIDS]).
8. Active infection requiring systemic treatment.
9. Pregnant or lactating.
10. Splenectomy, previous allogenic tissue/solid organ transplant.
11. Positive serological test of hepatitis B virus (HBV) or hepatitis C virus at
Screening.
- Subjects who test positive for anti-hepatitis C antibody (anti-HCV) but negative
for HCV ribonucleic acid (RNA) are considered eligible to participate in the
study.
- Subjects with infection of hepatitis B (positive hepatitis B surface antigen
[HBsAg] result) will be excluded. Subjects with a past or resolved HBV infection
(defined as the presence of hepatitis B core antibody [HBcAb] and absence of
HBsAg) are eligible.
12. 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 4 weeks 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.
13. Subjects with untreated and/or symptomatic metastatic central nervous system (CNS)
disease, primary CNS tumors, leptomeningeal disease or spinal cord compression.
However, subjects 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.
14. History of another primary malignant tumor, except the following: 1) the patient has
undergone potentially curative therapy with no evidence of that disease and recurrence
for 3 years prior to the first dose of study treatment; 2) Adequately treated
non-melanoma skin cancer or lentigo with no evidence of malignancy; 3) Adequately
treated carcinoma in situ without evidence of disease.
15. Subjects with moderate to large amount of pleural effusion, ascites or pericardial
effusion who need drug or medical intervention. Subject may be eligible to participate
following discussion with investigator and approval from the sponsor.
16. Unexplained >38.5? fever (If the fever is caused by the tumor according to the
investigator's judgment, the patient can be enrolled) occurs during the screening
period or on the day of administration, which in the judgment of investigator, would
interfere with patient participation in the study or evaluation of patient's efficacy.
17. History of seizure disorders within 6 months prior to Screening.
18. Active oral or skin herpes lesion at Screening.
19. Plan to receive any other anti-tumor therapy (including herbal therapy that has
anti-tumor effects) during treatment with study drug.
20. History of 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.
21. 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.
22. History of psychiatric disorders that would interfere with cooperation with the
requirements of the trial or is still requiring for medication control.
23. History of substance abuse (including alcohol) within 6 months prior to signing
informed consent.
24. 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.
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