| Eligibility |
Inclusion Criteria:
- Men and women aged 18 or older.
- Willingness to provide written informed consent for the study.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
- Have a life expectancy of at least 6 months
- Locally advanced or metastatic disease; locally advanced disease must not be amenable
to resection with curative intent.
- Disease progression after receipt of a prior systemic immunotherapy such as monoclonal
antibodies targeting PD-1, PD-L1, CTLA-4 or other immune modulators with or without
chemotherapy.
- Presence of measurable disease based on RECIST v1.1. Tumor lesions - situated in a
previously irradiated area, or in an area subjected to other locoregional therapy, are
not considered measurable unless there has been demonstrated progression in the
lesion.
- After dose escalation, subject must be willing to undergo pretreatment and
on-treatment tumor biopsies (core or excisional). Note: A baseline biopsy obtained for
other purposes (i.e., not an NC318-02 study procedure) before signing consent may be
utilized if the subject has not had any intervening systemic therapy from the time of
the biopsy to the start of treatment with the medical monitor's approval.
- Female subjects of childbearing potential (defined as women who have not undergone
surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not
postmenopausal, defined as = 12 months of amenorrhea) must have a negative serum
pregnancy test at screening. All female and male subjects of childbearing potential
must agree to take appropriate precautions to avoid pregnancy or fathering children
(with at least 99% certainty) from screening through 60 days after the last dose of
study drug.
Exclusion Criteria:
- Inability to comprehend or unwilling to sign the Informed Consent Form.
- Received more than 1 prior line of systemic anti-cancer therapy for Stage IIIB/IIIc/IV
or recurrent NSCLC disease (does not include adjuvant or neoadjuvant treatments).
- Requires concurrent radiation or other anticancer therapy
- Screening laboratory values of:
1. Absolute neutrophil count < 1.5 × 10^9/L
2. Platelets < 100 × 10^9/L
3. Hemoglobin < 9 g/dL or < 5.6 mmol/L
4. Serum creatinine > 1.5 × institutional upper limit of normal (ULN)
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN
6. Total bilirubin = 1.5 × ULN unless conjugated bilirubin = ULN (conjugated
bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no
institutional ULN, then direct bilirubin must be < 40% of total bilirubin.
7. International normalized ratio (INR) or prothrombin time (PT) > 1.5 × ULN
8. Activated partial thromboplastin time (aPTT) > 1.5 × ULN
- Transfusion of blood products (including platelets or red blood cells) or
administration of colony-stimulating factors (including granulocyte colony-stimulating
factor, granulocyte macrophage colony-stimulating factor, or recombinant
erythropoietin) within 14 days before the first administration of study drug.
- Receipt of anticancer medications or investigational drugs within the following
intervals before the first administration of study drug:
- = 21 days for chemotherapy or radiation therapy. Subjects must also not require
chronic use of corticosteroids and must not have had radiation pneumonitis
because of a treatment. A 1-week washout is permitted for palliative radiation to
non-central nervous system (CNS) disease with medical monitor approval. Note:
Bisphosphonates and denosumab are permitted medications.
- = 7 days for immune-suppressive-based treatment for any reason. Note: Use of
inhaled or topical steroids or corticosteroid use for radiographic procedures is
permitted. Note: The use of physiologic corticosteroid replacement therapy may be
approved after consultation with the medical monitor.
- = 28 days or 5 half-lives (whichever is longer) for prior ICI.
- Has not recovered to = Grade 1 from toxic effects of prior therapy (including prior
immunotherapy) and/or complications from prior surgical intervention before starting
therapy. Note: Subjects with stable chronic conditions (= Grade 2) not expected to
resolve (such as neuropathy and alopecia) are exceptions and may enroll. Note:
Subjects with a history of any grade immune-related ocular AE (e.g., episcleritis,
scleritis, uveitis) will be excluded. Note: Subjects with a history of a Grade 3 or
higher immune-related AE from prior immunotherapies are excluded.
- History of recurrent Grade 2 pneumonitis attributed to prior treatment with immune
checkpoint inhibitor therapy
- Receipt of a live vaccine within 30 days of planned start of study therapy. Note:
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin,
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,
FluMist®) are live attenuated vaccines and are not allowed.
- Active autoimmune disease that required systemic treatment in the past (i.e., with use
of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Subjects
who have not required systemic treatment in the past 2 years may be eligible with
approval of the medical monitor. Note: Subjects with hyper/ hypothyroidism are
eligible to participate. Note: Replacement and symptomatic therapies (e.g.,
levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal
or pituitary insufficiency, etc.) are not considered a form of systemic immune
suppressive therapy and are allowed.
- Known active CNS metastases and/or carcinomatous meningitis. Note: Subjects with
previously treated brain metastases may participate provided they are stable (without
evidence of progression by imaging for at least 28 days before the first dose of study
drug and any neurologic symptoms have returned to baseline), have no evidence of new
or enlarging brain metastases or CNS edema, and have not required steroids for at
least 7 days before the first dose of study drug.
- Known concurrent malignancy that is progressing or requires active treatment, or
history of other malignancy within 2 years of study entry apart from cured basal cell
or squamous cell carcinoma of the skin, superficial bladder cancer, prostate
intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or
indolent malignancy, or cancers from which the subject has been disease-free for > 1
year, after treatment with curative intent.
- Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's
opinion, is clinically meaningful.
- Active infection requiring systemic therapy.
- Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of
reactivation. HBV-DNA and HCV-RNA must be undetectable. Subjects cannot be positive
for HBV-DNA, HCV-RNA, hepatitis B surface antigen, or anti-hepatitis B core antibody.
Note: Subjects with no prior history of hepatitis B infection who have been vaccinated
against hepatitis B and who have a positive antibody against hepatitis B surface
antigen test as the only evidence of prior exposure may participate in the study.
- Known history of HIV (HIV 1 or HIV 2 antibodies).
- Known allergy or reaction to any component of study drug or formulation components.
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 60 days
after the last dose of study treatment.
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