| Eligibility |
Inclusion Criteria:
1. Male or female subjects aged = 18 years old
2. Subject must have histologically- or cytologically-confirmed diagnosis of unresectable
locally advanced or metastatic melanoma, pancreatic cancer, liver metastases from
colorectal cancer, breast cancer, and other solid tumors. (Part 1 and Part 2 Cohort A
will include patients who have solid tumors with cutaneous/subcutaneous tumor lesions,
such as melanoma, cutaneous squamous cell carcinoma, and cutaneous/subcutaneous
metastasis from pancreatic cancer, colorectal cancer, breast cancer etc. Part 2 Cohort
B will include patients who have visceral tumors.)
3. Subject has measurable disease as determined by RECIST version 1.1. At least 1 lesion
must be suitable for intratumoral (IT) injection. Lesions for injection must be = 10
mm and = 60 mm in longest diameter.
4. Subjects who have progressed on or are ineligible for available standard therapy are
eligible for this trial after the last dose of the previous treatment which is = 4
weeks or 5 half-lives (if required) before the first dose of study treatment. Note:
patients who have previously been treated with IMLYGIC (Talimogene laherparepvec,
T-Vec) are eligible after discontinuing the last dose of previous T-Vec treatment for
= 12 weeks before first dose of study treatment.
5. Subject has a predicted life expectancy = 12 weeks.
6. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. A female subject is eligible to participate if she is not pregnant and at least 1 of
the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to use an acceptable form of birth control method, including:
abstinence, hormonal contraception for at least 3 months in combination with a barrier
method, intrauterine device (placement at least 3 months prior to screening), cervical
cap, condoms with contraceptive gel/foam/cream, or surgical sterilization (tubal
ligation at least 6 months prior to screening or partner who had a vasectomy at least
6 months prior to screening).
8. Female subject must agree not to breastfeed starting at screening, throughout the
study period and 180 days after the final study IP administration.
9. Female subject must not donate ova starting at screening, throughout the study period
and for 180 days after the final study IP administration.
10. Male subject must agree to remain abstinent or use a condom throughout the study
period and for 180 days after the final study IP administration.
11. Male subject with female partner(s) of childbearing potential must agree to use
contraception during the treatment period and for at least 180 days after the final
study IP administration.
12. Male subject must not donate sperm during the treatment period and for at least 180
days after the final study IP administration.
13. Subject must be willing and able to comply with the study requirements including
prohibited concomitant medication restrictions.
14. Subject agrees not to participate in another interventional study while receiving
study IP.
15. Subject has the ability to understand and the willingness to sign a written informed
consent document.
Exclusion Criteria:
1. Subject has ongoing toxicity = Common Terminology Criteria for Adverse Events (CTCAE)
grade 2 attributable to prior antineoplastic therapies considered clinically
significant determined by the Investigator.
2. Subject has had major surgery = 4 weeks of screening.
3. Subject is concurrently participating in another interventional study or has received
an investigational product < 4 weeks or 5 half-lives (if required) prior to first IP
administration.
4. Subject with symptomatic central nervous system (CNS) metastases, except patients with
CNS lesions that have been treated and have no evidence of progression in the brain on
CT/MRI for = 3 months and have been off steroids for at least 4 weeks prior to first
IP administration.
5. Subject with active autoimmune disease requiring systemic therapy within past 2 years.
(e.g., systemic lupus erythematosus, Wegener syndrome (granulomatosis with
polyangiitis), Graves' disease, hypophysitis, etc.). The following are exceptions to
this criterion:
- Subject with vitiligo or alopecia
- Subject with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Childhood asthma that has resolved
- Any chronic skin condition that does not require systemic therapy
- Type 1 diabetes mellitus ?Note: Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
6. Subject with another malignancy that currently requires treatment.
7. Subject with tumors encasing major vascular structures such as the carotid artery,
tumors adjacent to vital neurovascular structures or tumors in locations that are at
high risk for AEs or otherwise not considered appropriate for IT injection.
8. Subject with inadequate organ and marrow functions meeting any of the below criteria:
- with ongoing continuous supportive treatment
- Leukocytes < 3000/µL
- Absolute neutrophil count < 1500/µL
- Platelets < 100,000/µL
- Hemoglobin (Hgb) < 9 g/dL
- International normalized ratio (INR) > 1.5 × ULN and/or activated partial
thromboplastin time (aPTT) > 1.5 × institutional normal limits, except for
patients in Group B (Visceral Lesions) escalation and expansion groups where INR
and aPTT must be normal
- Total Bilirubin (TBL) > 1.5 × institutional normal limits (subjects with known
Gilbert syndrome who are excluded if TBL > 3.0 × institutional normal limits or
direct bilirubin > 1.5 × institutional normal limits)
- Aspartate aminotransferase (AST) and Alanine transaminase (ALT) > 3.0 ×
institutional normal limits. Subjects with tumors in the liver AST and ALT > 5 ×
institutional normal limits.
- Albumin < 3.0 g/dL
- Creatinine > 1.5 × institutional normal limits
9. Subject with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of first administration of study IP. Inhaled or topical steroids and adrenal
replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
active autoimmune disease.
10. Subject has an uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, any form of
substance abuse or psychiatric illness/social situations that would limit compliance
with study visits or requirements, or a condition that could invalidate communication
with the Investigator.
11. Subject is known to be positive for human immunodeficiency virus, hepatitis B surface
antigen, hepatitis B core immunoglobulin or immunoglobulin G (IgG) antibody, or
hepatitis C (IgG or ribonucleic acid (RNA) test) indicating acute or chronic
infection. HbsAg positive subject should further undergo hepatitis B virus (HBV) DNA
titer detection. For HCV antibody positive subject, further HCV RNA testing is
required. However, subject with the following conditions can be included in this
study: Hepatitis B surface antigen (HBsAg) is negative; if HBcAb is positive, HBV-DNA
(HBV deoxyribonucleic acid) < 200 IU/mL (or 1000 copies/mL).
12. Subject has a history of moderate to severe ascites, clinically significant and/or
rapidly accumulating ascites, bleeding esophageal varices, hepatic encephalopathy, or
pericardial and/or pleural effusions related to liver insufficiency within 6 months of
screening. Mild ascites that does not preclude safe IT injection of OH2 is allowed.
13. Subject has a clinically significant abnormal electrocardiogram (ECG) at screening.
14. Subject has symptomatic cardiovascular disease within the preceding 12 months unless
cardiology consultation and clearance has been obtained for study participation,
including but not limited to the following: significant coronary artery disease (e.g.,
requiring angioplasty or stenting), acute myocardial infarction or unstable angina
pectoris < 3 months prior to screening, uncontrolled hypertension, clinically
significant arrhythmia, or congestive heart failure (New York Heart Association grade
= 2).
15. Subject who has a history of bleeding diathesis, are on anti-coagulation therapy, or
have abnormal coagulation-fibrinolytic parameters (e.g., activated partial
thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and platelet
count).
16. Subject has medical conditions that predispose the subject to untoward medical risk in
the event of volume loading (e.g., intravenous fluid bolus infusion), tachycardia, or
hypotension during or following treatment with OH2.
17. Subject has a known or suspected hypersensitivity to OH2 or any components of the
formulation used, including prior adverse reaction to vaccinia (e.g., as smallpox
vaccine).
18. Subject has had previous exposure with OH2.
19. Active herpetic skin lesions or prior complications of herpetic infection (e.g.,
herpetic keratitis or encephalitis).
20. Requires intermittent or chronic systemic (intravenous or oral) treatment with an
antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
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