General
Inclusion Criteria:
- - ≥ 18 years of age at the time of screening.
- - Mentally competent and able to understand and sign the informed consent form (ICF).
- - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- - Life expectancy of ≥ 12 weeks per the Investigator.
- - At least 4 weeks from any prior major surgery.
- - Willing and able to provide blood samples prior to the start of this study.
- - Has a tumor lesion amenable to injection, must be accessible for pre and post
injection biopsy, and the patient must be willing to consent to biopsy, if deemed
safe by the Investigator.
- - Laboratory values (Hematology): Absolute neutrophil count ≥ 1,000 cells/mm3;
Platelet count ≥ 75,000 cells/mm3; Hemoglobin ≥ 8.0 g/dL.
- - Laboratory values (Renal): Serum creatinine < 1.5 × upper limit of normal (ULN) or
creatinine clearance ≥ 40 mL/min based on the Cockcroft-Gault glomerular filtration
rate estimation.
- - Laboratory values (Coagulation): Prothrombin/International Normalized Ratio (PT/INR)
or prothrombin time must be < 1.5 × ULN;
- Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless undergoing
anticoagulation therapy.
- - Laboratory values (Liver): Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 2 × ULN; Bilirubin ≤ 2 × ULN or ≤ 5 × ULN with liver
metastasis.
Phase 1
Inclusion Criteria:
- - Histologically or cytologically documented, locally advanced, or metastatic solid
tumor.
- - Disease progression confirmed by imaging or other objective evidence after having
received standard treatment or patients with refractory solid tumors.
Patients must
have progressed or are intolerant of at least one line of prior therapy.
Phase 2 Inclusion Criteria (TNBC):
- - Histologically or cytologically documented findings consistent with TNBC not
amenable to curative surgery, radiation, or other therapy.
- - Prior treatment (for advanced, metastatic or [neo]adjuvant) should have included a
taxane and/or anthracycline-based therapy and, where appropriate, an approved
checkpoint inhibitor.
- - Has disease other than the injected lesion that is measurable by RECIST 1.1.
Phase 2 Inclusion Criteria (melanoma):
- - Histologically or cytologically documented findings consistent with advanced
melanoma not amenable to curative surgery, radiation, or other therapy.
Uveal
melanoma is excluded.
- - Patients who are not candidates for or have refused available therapies are also
eligible.
- - Received an anti-programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1)
inhibitor as monotherapy or in combination with anti-cytotoxic lymphocyte associated
protein 4 (CTLA-4) inhibitor and have either primary or secondary checkpoint
inhibitor resistance as per Society for Immunotherapy of Cancer (SITC) consensus
definition, unless deemed intolerable by the investigator.
Patients with BRAF V600E
mutant melanoma should have received a BRAF inhibitor as monotherapy or in
combination with other targeted agents (mitogen-activated protein kinase [MAPK]
kinase [MEK] inhibitors), unless deemed intolerable by the investigator.
- - Has disease other than the injected lesion that is measurable by RECIST 1.1.
Phase 1 and 2
Exclusion Criteria:
- - History of primary immune deficiency.
- - History of autoimmune disease and/or requiring immunosuppression (except
hypothyroidism).
- - History of History of Grade 3 or higher immune-related adverse events.
Patient may
be enrolled with Medical Monitor approval.
- - History of solid organ transplant and taking immunosuppressive medications.
- - Cardiovascular exclusions: Medical history of an arterial thrombotic event, stroke,
or transient ischemic attack within the past 12 months; medical history of
symptomatic congestive heart failure (New York Heart Association classes II-IV) or a
cardiac arrhythmia that required treatment within the past 12 months; medical
history of myocardial infarction or unstable angina within 6 months before Cycle 1
Day 1; QTcF prolongation to > 470 ms in women and > 450 ms in men based on a 12-lead
electrocardiogram (ECG) in triplicate using the Fridericia formula: QTc = QT /
RR1/3.
Recent medical concerns exclusions:
- - Prior direct radiation therapy to the tumor lesion to be injected.
- - Active use of systemic anticoagulants.
- - Evidence of active infection requiring intravenous (IV) antibiotics during screening
requiring therapy within 7 days prior to Cycle 1 Day 1.
- - Active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to Cycle 1
Day 1.
- - Serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture
within 7 days prior to Cycle 1 Day 1.
- - Known human immunodeficiency virus (HIV) infection, active hepatitis B infection, or
hepatitis C infection.
- - Virology evaluation should be conducted at screening to include serum HIV antibody,
HBc antibody, HBsAg antigen, and HCV antibody.
Patients with a positive antibody
evaluation for HCV and/or HBc should undergo evaluation to measure HCV RNA or HBV
DNA, respectively.
- - Untreated central nervous system tumor, epidural tumor or metastasis, or brain
metastasis.
Patients with any primary Central Nervous System (CNS) malignancy
including glioma and current, active, progressing CNS malignancy, including
carcinomatosis meningitis are excluded.
- - Patients with treated brain metastases are eligible if there is no evidence of
progression for at least 4 weeks after CNS-directed treatment, as ascertained by
clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed
tomography [CT] scan) during the screening period and off systemic steroids (for at
least 2 weeks prior to first dose).
- - Another primary malignancy that has not been treated with curative intent, except
for non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscle
invasive bladder cancer.
- - Serious illness considered by the Investigator as incompatible with participating in
this clinical study.
- - Any condition that, in the opinion of the Investigator, would interfere with
evaluation of the investigational product or interpretation of the patient's safety
or study results.
- - Receipt of any vaccine within 30 days prior to the first dose of study treatment.
- - Use of another anticancer therapy within 3 weeks prior to Cycle 1 Day 1 or 5
half-lives, whichever is shorter.
- - Previously enrolled in this study.
- - Actively enrolled in another clinical study unless it is an observational
(noninterventional) clinical study or the follow-up component of an interventional
study.
- - Known severe hypersensitivity (Grade ≥ 3) to study treatment or any of the
excipients of the products.
- - Known psychiatric or substance use disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
- - Currently pregnant (confirmed with positive pregnancy test), breast-feeding or
planning to become pregnant within 60 days following treatment.
For women of
childbearing potential (WOCBP), a negative serum beta-human chorionic gonadotropin
(β-HCG) result must be available within a 72 hour window before the first treatment
dose.
- - Women of childbearing potential not willing to use a highly effective method of
contraception.
- - Unwilling or unable to follow protocol requirements.
