| Eligibility |
Inclusion Criteria:
- Men and women aged 18 or older.
- Willingness to provide written informed consent for the study.
- ECOG performance status 0 to 1.
- Locally advanced or metastatic disease; locally advanced disease must not be amenable
to resection with curative intent.
- Subjects who have disease progression after treatment with available therapies that
are known to confer clinical benefit, or who are intolerant to treatment, or who
refuse standard treatment. Note: There is no limit to the number of prior treatment
regimens.
- 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.
- Phase 1a Dose Escalation (optional), Phase 1b Safety Expansion, and Phase 2
(mandatory): Willingness to undergo pretreatment and on-treatment tumor biopsies (core
or excisional).
- 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) and non-sterilized 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
90 days after the last dose of study drug. Females of child-bearing potential must
have a negative serum pregnancy test at screening.
Exclusion Criteria:
- Inability to comprehend or unwilling to sign the ICF.
- Laboratory and medical history parameters not within the protocol-defined range.
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) and measured
or calculated creatinine clearance < 50 mL/min for subjects with creatinine
levels > 1.5 × institutional ULN.
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN.
With the following exceptions: subjects with documented liver metastases AST
and/or ALT = 5 × ULN. Patients with documented liver or bone metastases: alkaline
phosphatase = 5 ×ULN.
6. Total bilirubin = 1.5 × ULN.
7. International normalized ratio (INR) or prothrombin time (PT) > 1.5 × ULN;
Activated partial thromboplastin time (aPTT) > 1.5 × ULN, except for subjects on
anticoagulation.
- 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 7 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:
1. = 14 days for chemotherapy, targeted small molecule therapy, hormonal therapy or
radiation therapy. Subjects 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.
2. = 28 days for prior immunotherapy or persistence of active cellular therapy
(e.g., chimeric antigen receptor T cell therapy; other cellular therapies must be
discussed with the medical monitor to determine eligibility).
3. = 28 days for a prior mAb used for anticancer therapy except for denosumab.
4. = 7 days for immune-suppressive-based treatment for any reason.
5. = 28 days or 5 half-lives, t½, (whichever is longer) before the first dose for
all other investigational study drugs or devices. For investigational agents with
long half-lives (e.g., > 5 days), enrollment before the fifth t½ requires medical
monitor approval.
6. = 14 days for a COVID-19 vaccine. Note: For 2-dose vaccines, subjects must wait
at least 14 days after administration of the 2nd dose of the vaccine prior to
receiving the first dose of the study drug.
- Has not recovered to = Grade 1 from toxic effects of prior therapy (including prior
immunotherapy and radiation therapy) and/or complications from prior surgical
intervention before starting therapy.
- Receipt of a live vaccine within 30 days of planned start of study therapy.
- Active autoimmune disease that required systemic treatment in the past (i.e., with use
of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- Known active CNS metastases and/or carcinomatous meningitis.
- Known concurrent malignancy that is progressing or requires active treatment, or
history of other malignancy within 2 years of study entry.
- Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
- Documented known activating or driver mutations (i.e. EGFR mutations/amplification,
BRAF mutations, ALK alterations, etc.) which have not been previously treated with a
standard of care targeted therapy.
- Subjects with screening QTc interval > 470 milliseconds (corrected by Fridericia) are
excluded.
- Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate
anti-infection treatment.
- Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis
is considered to be cured.
- 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 90 days
after the last dose of study treatment.
- Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study drug and attending
required study visits; pose a significant risk to the subject; or interfere with
interpretation of study data.
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