Phase 1 study to assess the safety, preliminary efficacy of PD-L1 t-haNK and to determine the
maximal tolerated dose and designate the recommended phase 2 dose for subjects with locally
advanced or metastatic solid cancers. The study will be conducted in 2 parts: part 1 will
involve dose escalation and part 2 will involve expansion of the recommended phase 2 dose.
Inclusion Criteria:
1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
3. Have histologically confirmed unresectable, locally advanced or metastatic solid
cancer regardless of tumor PD-L1 expression levels.
4. Have received treatment with at least 1 prior line of therapy in the metastatic
setting or not be a candidate for therapy of proven efficacy for their disease. Prior
immune therapy and prior treatment with a checkpoint inhibitor as per FDA indication
for current standard-of-care therapy is allowed.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
6. Have at least 1 measurable lesion and/or non-measurable disease evaluable in
accordance with RECIST Version 1.1.
7. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen
obtained following the conclusion of the most recent anticancer treatment and be
willing to release the specimen for exploratory tumor molecular profiling. If an
historic specimen is not available, the subject must be willing to undergo a biopsy
during the screening period, if considered safe by the Investigator. If safety
concerns preclude collection of a biopsy during the screening period, a tumor biopsy
specimen collected prior to the conclusion of the most recent anticancer treatment may
be used.
8. Must be willing to provide pre- and post-infusion blood samples for exploratory
analyses.
9. Ability to attend required study visits and return for adequate follow-up, as required
by this protocol.
10. Agreement to practice effective contraception for female subjects of child-bearing
potential and non-sterile males. Female subjects of child-bearing potential must agree
to use effective contraception while on study and for at least 5 months after the last
dose of PD-L1 t-haNK for Infusion. Non-sterile male subjects must agree to use a
condom while on study and for up to 5 months after the last dose of PD-L1 t-haNK for
Infusion. Effective contraception includes surgical sterilization (eg, vasectomy,
tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
spermicide, intrauterine devices (IUDs), oral contraceptives, and abstinence.
Exclusion Criteria:
1. Body weight ≤ 50 kg at screening.
2. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk for
treatment- related complications.
3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
disease, autoimmune disease associated with lymphoma).
4. History of organ transplant requiring immunosuppression.
5. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis).
6. Inadequate organ function, evidenced by the following laboratory results:
1. Absolute neutrophil count (ANC) < 750 cells/mm3.
2. Platelet count < 75,000 cells/mm3.
3. Hemoglobin < 9 g/dL.
4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject
has documented Gilbert's syndrome).
5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
6. Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases, or >10 × ULN in subjects with bone metastases).
7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
7. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication.
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
continuous oxygen therapy.
9. Positive results of screening test for human immunodeficiency virus (HIV).
10. Current chronic daily treatment (continuous for > 3 months) with systemic
corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
11. Known hypersensitivity to any component of the study medication(s).
12. Participation in an investigational drug study or history of receiving any
investigational treatment within 14 days prior to dosing for this study, except for
testosterone-lowering therapy in men with prostate cancer.
13. Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.
14. Concurrent participation in any interventional clinical trial.
15. Pregnant and nursing women. A negative serum pregnancy test during screening and a
negative pregnancy test within 72 hours prior to the first dose must be documented
before PD-L1 t-haNK for Infusion is administered to a female subject of child-bearing
potential.
