A Study of NILK-2301 in Patients with Locally Advanced or Metastatic Low Tumor Volume (LTV) Colorectal Cancer

Inclusion criteria

• Adults ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed diagnosis of CRC.
• Patients with locally advanced or metastatic disease

• after at least 1 prior systemic treatment for the primary malignancy
• and who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer a clinical benefit to patients with these tumor entities.
• Measurable disease according to the revised RECIST guideline version 1.1 (5).
• Tumor lesions of up to approximately 50 cc estimated with the sum of all measurable lesions (excluding pathological lymph nodes) longest diameter (SLD). SLD should be < 7 cm.
• Any measurable lesion (excluding pathological lymph nodes) longest diameter ˂ 5 cm.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
• Subjects must have the following laboratory values (determined by local lab):

• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L, the use of colony- stimulating factors, i.e., granulocyte colony-stimulating factor (G-CSF) or GM-CSF, within 14 days before the test is not allowed.
• Platelets ≥ 100 x 109/L, transfusion support within 14 days before the test is not allowed.
• Hemoglobin ≥ 10 g/dL. Prior RBC transfusion is permitted.
• Potassium within normal limits or correctable with supplements.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN), or Alkaline Phosphatase (ALP) ≤ 3 × ULN
• Serum bilirubin < 1.5 x ULN.
• Calculated glomerular filtration rate of ≥ 45 mL/min/1.73 m2, according to the MDRD abbreviated formula.
• International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT)< 1.5 x ULN.
• Females of childbearing potential (FCBP) must:

• have two negative urine or serum pregnancy tests as verified by the Investigator prior to starting NILK-2301; the subject may not receive NILK-2301 until the Investigator has verified that the result of the pregnancy test is negative. A urine or serum pregnancy test is required at screening and within 72 hours prior to dosing on Cycle 1, Day 1, and within 72 hours prior to Day 1 of every subsequent cycle. Note: the Cycle 1, Day 1 pregnancy test does not need to be repeated if the screening pregnancy test was done within 72 hours prior to dosing. A serum or urine pregnancy test (Investigator's discretion) must also be performed at the end of study for each FCBP; and
• agree to use and be able to comply with a highly effective birth control method, i.e., one that can achieve a failure rate of less than 1% per year when used consistently and correctly, from signing the ICF, throughout the study, and for up to 28 days following the last dose of NILK-2301

Exclusion criteria

• Patient has known hypersensitivity to NILK-2301 or any of the constituent compounds.
• Patients with CNS lesions and / or bone disease.
• Patients with pleural and / or pericardial tumor lesions.
• Radiotherapy to the target lesions within 4 weeks prior to the first NILK- 2301 infusion.
• Prior anti-cancer therapy including chemotherapy, hormonal therapy, and investigational agents within 28 days prior to starting NILK-2301 dosing. Note: low dose steroids (oral prednisone or equivalent ≤ 10 mg per day, including systemic or topic use), localized non-central nervous system (CNS) radiotherapy of non-target lesions, and treatment with bisphosphonates and RANKL inhibitors are not criteria for exclusion.
• Other investigational therapies must not be used, i.e., treatment within another clinical trial is not permitted, while the patient is on study. COVID- 19 vaccination is allowed only starting from Cycle 2 (if not completed before study inclusion).
• Severe cardiac dysfunction (NYHA classification III-IV).
• Significant hepatic dysfunction (serum bilirubin ≥ 1.8 mg/dL or AST and/or ALT ≥ 2.5 times ULN), or ALP ≤ 3 × ULN.
• Patients with known human immunodeficiency virus (HIV) infection or known history or serological evidence of hepatitis B or C virus infection.
• Uncontrolled active systemic bacterial, viral, fungal, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks prior to first dose of NILK-2301.
• Confirmed history or current autoimmune disease or other diseases or conditions resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy. Low- dose steroids (oral prednisone or equivalent ≤ 10 mg per day) for rheumatoid arthritis or similar conditions are allowed.
• Patients with concomitant active malignancy requiring ongoing systemic treatment.
• Patients with CNS metastases, history of leptomeningeal disease, or seizure disorder requiring therapy (e.g., steroids or anti-epileptics).
• ANC < 1 x 109/L (the use of colony stimulating factors, G-CSF or GM-CSF, within 14 days before the test is not allowed).
• Pregnancy and lactation.
• History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements or give informed consent.
• Significant medical diseases or conditions, including laboratory abnormalities, as assessed by the Investigators and Sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, myocardial infarction within the last 6 months, unstable angina or unstable life-threatening arrhythmias, uncontrolled diabetes mellitus, severely immunocompromised state, and major surgery ≤ 4 weeks prior to starting NILK-2301.
• Patients in whom acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure have not resolved to Grade ≤ 1 or returned to baseline except for alopecia (any grade), anemia, and peripheral neuropathy (for the latter, recovery to Grade ≤ 2 is acceptable).
• Exposure to live or live attenuated vaccine within 28 days prior to signing the ICF.
• Previous treatment with a CEACAM5 targeting agent.
• Prior treatment with a T-cell bispecific antibody or CAR T-cells.