This is a two-part, open-label phase 1 study to evaluate safety and preliminary efficacy of
M-CENK and N-803 for subcutaneous administration, cryopreserved in subjects with locally
advanced or metastatic solid tumors. The study consists of two cohorts: cohort 1 includes
subjects with newly diagnosed high-risk solid tumors who have not received prior treatment
for high-risk tumors; and cohort 2 includes subjects with relapsed/refractory (r/r) solid
tumors who have progressive disease after receiving ≥ 2 prior therapies. The two cohorts will
be conducted simultaneously.
Inclusion Criteria:
- Age ≥ 18 years old.
- Able to understand and provide a signed informed consent that fulfills the relevant
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
- Have histologically confirmed unresectable, locally advanced or metastatic solid
tumor.
- For subjects with genetic mutations or alterations in solid tumors (e.g. NSCLC,
pancreatic cancer, melanoma), the subjects must have received prior appropriate
disease specific targeted therapy and have progressed.
- For subjects with a history of HIV
- Subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL and without a history of AIDS
defining opportunistic infections are eligible.
- For subjects with a history of HBV
- Subjects who are chronic carriers of HBV infection (HBsAg-positive, undetectable or
low HBV DNA, and normal ALT) who are not on HBV therapy, or in individuals who have
serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and
anti-HBc-positive), anti-HBV prophylaxis should be assessed prior to enrollment.
- Subjects with chronic HBV infection with active disease who meet the criteria for anti
HBV therapy should be on a suppressive antiviral therapy prior to enrollment.
- For subjects with a history of HCV
- Subjects with a history of HCV infection should have completed curative antiviral
treatment and have a HCV viral load below the limit of quantification are eligible.
- Subjects who are HCV Ab positive but HCV RNA negative due to prior treatment or
natural resolution are eligible.
- Subjects on concurrent HCV treatment and have HCV below the limit of quantification
are eligible.
Note: Subjects who have a history of HIV/HBV/HCV or are seropositive will require
Infectious Disease Marker (IDM) testing prior to apheresis collection.
- Subjects with previously treated and who currently have non-progressive brain
metastasis may participate in this study.
- Able to undergo an Apheresis procedure:
- Has adequate venous access
- Able to sit or recline for 5-6 hours with limited movement
- Hemoglobin must be ≥ 9.0 g/dL
- Platelet count must be ≥ 100 cells/mm3
- Vital signs must be within normal range
- Negative pregnancy test for females of childbearing potential.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Cohort 2 subjects only:
- Have received treatment with at least 2 prior lines 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.
- Have at least 1 measurable lesion and/or non-measurable disease evaluable in
accordance with RECIST Version 1.1.
- Ability to attend required study visits and return for adequate follow-up, as required
by this protocol.
- Agreement to practice effective contraception for female subjects of child-bearing
potential and nonsterile males.
Exclusion Criteria:
Cohort 2 subjects only:
- 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.
- Currently receiving antibiotics for a recent infection.
- Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
disease, autoimmune disease associated with lymphoma) requiring medical treatment
- History of organ transplant requiring immunosuppression.
- History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis), unless the inflammation is well controlled.
- Inadequate organ function, evidenced by the following laboratory results:
- Absolute neutrophil count (ANC) < 1500 cells/mm3.
- Platelet count < 100,000 cells/mm3.
- Hemoglobin < 9 g/dL.
- Total bilirubin greater than 1.5 x the upper limit of normal (ULN; unless the subject
has documented Gilbert's syndrome).
- Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5
× ULN (> 5 × ULN in subjects with liver metastases).
- Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases, or >10 × ULN in subjects with bone metastases).
- Serum creatinine > 2.0 mg/dL or 177 μmol/L.
Note: Each site should use its own institution's upper limit of normal (ULN) to determine
eligibility.
- For subjects who have received approved chemotherapy or approved immunotherapy, a
repeat CBC a least 14 days after completion of the treatment to demonstrate recovery
of counts to an ANC ≥1000 and Platelets ≥100,000 is required.
- For subjects who have received investigational chemotherapy or investigational
immunotherapy, a repeat CBC a least 30 days after completion of the treatment to
demonstrate recovery of counts to an ANC ≥ 1000 and Platelets ≥ 100,000 is required.
- 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.
- Dyspnea at rest due to complications of advanced malignancy or other disease requiring
continuous oxygen therapy. Oxygen therapy on an as needed or intermittent basis is
allowed.
- 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.
- Known hypersensitivity to any component of the study medication(s).
- Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.
- Concurrent participation in any interventional clinical trial.
- 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 M-CENK is administered to a female subject of childbearing potential.
