Inclusion Criteria
Each patient must meet all the following criteria to participate in the study:
1. Age ≥ 18 years, able to understand and voluntarily sign a written informed consent form (ICF)
and willing and able to comply with protocol requirements
2. Minimum body weight ≥47 kilograms (103 pounds)
3. For all patients in the dose escalation (Part 1): A confirmed diagnosis of a r/r locally advanced
or metastatic solid tumor for which the patient has progressed on or is intolerant of standard
therapy, or for whom no standard therapy with proven benefit exists. Patients with castrate-
resistant prostate cancer (CRPC) and primary CNS malignancies are ineligible. Patients with
non-Hodgkin lymphoma (NHL) will not be enrolled in the dose escalation but are eligible for
the dose expansion.
4. For all patients in the dose expansion (Part 2): A confirmed diagnosis of a r/r locally advanced
or metastatic cutaneous melanoma, MSS CRC or NHL for which the patient has progressed
on or is intolerant of standard therapy. The dose expansion consists of 3 arms (A, B and C)
with the following eligibility criteria:
• Arm A: Patients with locally advanced or metastatic cutaneous melanoma who
demonstrate either primary or secondary resistance to checkpoint inhibitor (CPI)
therapy are eligible for Arm A. Primary resistance is defined as disease progression or
stable disease (SD) to inhibitors of PD-(L)1. Secondary resistance is defined as disease progression ≥ 6
months after initiation of PD-(L)1 inhibitors in patients who have received clinical
benefit, defined as a complete response (CR) or partial response (PR) per RECIST 1.1,
or SD > 6 months. Patients who discontinued CPI therapy due to toxicity or for other
reasons or who haven’t demonstrated either primary or secondary resistance to CPIs
are ineligible. Patients with mucosal or uveal melanoma are also ineligible. Patients
must have received at least 1 prior line that was a SOC CPI regimen and are allowed
no more than 3 prior lines for advanced disease. Patients with additional lines of prior
therapy but good/excellent performance status may be considered but only after
discussion with the Sponsor. Prior therapy with BRAFi/MEKi is not required.
(Neo)adjuvant therapy is considered a prior line if a patient progressed while receiving
treatment or relapsed within 6 months of the last dose. Prior T-VEC therapy is allowed
and does not count as a prior line, but treated lesions cannot be used as target lesions
or accessed for mandatory pre- and on-treatment biopsies.
• Arm B: Patients with r/r locally advanced or metastatic MSS CRC who are
immunotherapy naïve. Prior testing must demonstrate lack of tumor mismatch repair
deficiency (dMMR) and/or microsatellite instability (MSI-H) using a clinically
approved assay. Patients should have had no more than 3 prior lines of therapy in the
advanced/metastatic setting and must have either progressed on or be intolerant of the
following agents: fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab (or other
anti-VEGF therapy), an anti-epidermal growth factor receptor (EGFR) antibody (i.e.,
cetuximab or panitumumab, when indicated), and targeted therapy (when indicated).
Prior therapy with regorafenib, fruquintinib or trifluridine/tipiracil (TAS-102) is
allowed but not required. Patients should NOT have previously received inhibitors of
PD-(L)1 or CTLA-4, or any investigational immunotherapies. (Neo)adjuvant therapy
is considered a prior line if a patient progressed while receiving treatment or relapsed
within 6 months of the last dose. Patients with liver metastases are eligible but may be
limited in number based on evolving data.
• Arm C: Patients with advanced NHL who have follicular lymphoma or DLBCL. Other
subtypes of NHL may be considered after discussion with the Sponsor. All patients
with NHL must have received at least 2 prior systemic therapies and have relapsed or
refractory disease. Prior therapy with autologous CAR-T therapy is permitted and will
be considered a prior line.
o Patients with follicular lymphoma (or other indolent lymphoma) must meet at
least one criterion to begin treatment per Groupe d'Etude des Lymphomes
Folliculaires (GELF). These criteria include: 1. involvement of ≥ 3 nodal sites,
each with a diameter of ≥ 3 cm; 2. any nodal or extranodal tumor mass with a
diameter of ≥ 7.0 cm; 3. B symptoms; 4. splenomegaly; 5. pleural effusions or
peritoneal ascites; 6. cytopenias (leukocytes 100 x 109/L); and 7. leukemia (> 5.0 x 109/L malignant cells). Patients who do
not meet at least one criterion per GELF (i.e., low tumor burden) are eligible
for treatment only if they have symptomatic disease.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
6. At least one measurable lesion per RECIST 1.1 (Appendix D; Eisenhauer et al., 2009) or
evaluable lesion per Lugano classification (Cheson et al., 2014).
7. Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic tumor
lesion.
8. Human immunodeficiency virus (HIV) infected patients must be on antiretroviral therapy
(ART). Patients on ART must have well-controlled HIV infection/disease as evidenced by the
following:
a. A CD4+ T-cell count > 350 cells/mm 3 at time of screening.
b. Achieved and maintained virologic suppression defined as confirmed HIV RNA level
below 50 copies/mL or the lower limit of qualification (below the limit of detection) using
the locally available assay at the time of screening and for at least 12 weeks prior to
screening.
c. Been on a stable regimen, without changes in drugs or dose modification, for at least
4 weeks prior to study entry (Day 1).
9. Has adequate organ and bone marrow function defined by:
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (≥ 1500/mm 3 ).
b. Hemoglobin ≥ 9.0 g/dL or equivalent. Criteria must be met without packed red blood cell
transfusion within the prior 2 weeks.
c. Platelet count ≥ 100 × 109 /L (100,000/mm3 ).
d. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) in the absence of Gilbert’s syndrome
and ≤ 3 × ULN if the patient has Gilbert’s syndrome.
e. Measured or calculated creatinine clearance (estimated glomerular filtration rate)
≥ 30 mL/min.
f. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or
≤ 5 × ULN for patients with hepatic metastases.
10. Willingness of men and women of reproductive potential to agree to highly effective birth
control for the duration of treatment and for 4 months following the last dose of study drug.
Note: A postmenopausal woman will be defined as having no menses for 12 months without
an alternative medical cause. Male sterility will be defined as only men sterilized surgically.
For male patients with a pregnant female partner, a condom should be used for contraception.
For male patients with a non-pregnant female partner of childbearing potential and women of
childbearing potential, one of the following birth control methods with a failure rate of less
than 1% per year when used consistently and correctly are recommended:
a. Combined estrogen and progesterone containing hormonal contraception associated with
inhibition of ovulation given orally, intravaginally, or transdermally.
b. Progesterone-only hormonal contraception associated with inhibition of ovulation given
orally, by injection, or by implant.
c. Intrauterine device.
d. Intrauterine hormone-releasing system.
e. Bilateral tubal occlusion.
f. Vasectomized partner.
g. Sexual abstinence.
Note: Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk associated with
the study treatments. The reliability of sexual abstinence needs to be evaluated in relation
to the duration of the clinical study and the preferred and usual lifestyle of the patient.
Birth control methods unacceptable for this clinical study are:
a. Periodic abstinence (calendar, symptothermal, or post-ovulation methods).
b. Withdrawal (coitus interruptus).
c. Spermicide only.
d. Lactational amenorrhea method.
e. Condom.
Male study participants should refrain from sperm donation during study treatment and up to
6 months following the last dose of study drug.
A woman of childbearing potential is a woman who is fertile following menarche and until
becoming post-menopausal unless permanently sterile. Permanent sterilization methods
include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
 

Exclusion Criteria
Patients who meet any of the following criteria will be excluded from participating in the study:
1. A history of another active malignancy (a second cancer) within the previous 2 years, except
for localized cancers that are not related to the current cancer being treated, is considered
cured, and, in the opinion of the Investigator, presents a low risk of recurrence. These
exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial
bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
2. Received prior treatment with IL-12 by any route of administration (including intratumoral
injection).
3. Patients with primary CNS malignancies and CRPC are excluded from all parts of the trial.
Patients with NHL are excluded from the dose escalation. Patients with uveal and mucosal
melanoma are excluded from dose expansion Arm A.
4. Have known symptomatic brain metastases requiring steroids. Patients with previously
diagnosed brain metastases are eligible if they have completed their treatment, have recovered
from the acute effects of radiation therapy or surgery prior to enrollment and are neurologically
stable and asymptomatic from their CNS metastases.
5. Significant cardiovascular disease, including myocardial infarction, arterial
thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to the first
dose of study drug; symptomatic dysrhythmias or unstable dysrhythmias requiring medical
therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart
Association Class 3 or 4 congestive heart failure; or history of congenital prolonged QT
syndrome.
6. Significant electrocardiogram (ECG) abnormalities at Screening, including unstable cardiac
arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular
(AV) block type II, third-degree AV block, ≥ Grade 2 bradycardia, or QT interval corrected
for heart rate using Fridericia’s formula (QTcF) > 470 msec.
7. Active autoimmune disease requiring systemic treatment in the past 2 years (i.e., with use of
disease-modifying antirheumatic agents or immunosuppressive drugs).
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal, thyroid, or pituitary insufficiency) is permitted.
8. Diagnosis of immunodeficiency, on immunosuppressive therapy, or receiving chronic
systemic or enteric steroid therapy (dose > 10 mg/day of prednisone or equivalent) or any other
form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Note: At screening and during study participation, patients may be using systemic
corticosteroids (dose ≤ 10 mg/day of prednisone or equivalent) or topical or inhaled
corticosteroids.
9. In patients with NHL, prior receipt of an allogeneic stem cell transplant or prior allogeneic
CAR-T cell therapy. (Autologous stem cell transplantation and autologous CAR-T cell therapy
are allowed, but at least 100 days must have elapsed from the receipt of autologous HSCT or
autologous CAR T-cell therapy prior to the start of study drug and patients must have
completely recovered from the acute toxicities of these treatments).
10. Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose
of study drug.
11. Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine, or other anticancer herbal remedy) within
5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug. In addition,
no concurrent investigational anticancer therapy is permitted during the study.
12. Radiotherapy within 2 weeks of start of study treatment. Participants must have recovered
from all radiation-related toxicities and not require corticosteroids. A 1-week washout is
permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
13. Any unresolved toxicities from prior therapy greater than National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Grade 1 at the time of
starting study drug except for alopecia, Grade 2 platinum therapy-related neuropathy and
Grade 2 endocrine immune-related AEs managed with a stable dose of hormone replacement
therapy.
14. Use of sensitive substrates of major CYP450 isozymes.
Note: A list of substrates which are sensitive to these enzymes is provided in Appendix B. If
a sensitive substrate cannot be stopped and replaced with another medication, the patient’s
inclusion in the study should be discussed with the Sponsor.
15. Any illness, medical condition, organ system dysfunction, or social situation, including mental
illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s
ability to sign the ICF, adversely affect the patient’s ability to cooperate and participate in the
study, or compromise the interpretation of study results.
16. Received a live vaccine within 30 days of the first dose of study drug.
17. Active systemic bacterial, viral, or fungal infection.
18. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman
Disease.
19. Active infection as determined by hepatitis B surface antigen and hepatitis B core antibody, or
hepatitis B virus deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction
(qPCR) testing.
20. Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR
testing.
21. Pregnant or lactating.
Note: Defined as a WOCBP who has a positive urine pregnancy test (within 72 hours) prior
to treatment. If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
22. History of hypersensitivity to any of the study drug components.