Study of DNP002 in Patients With Solid Tumors

This is an open-label, Phase 1, first-in-human, dose-escalation study designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of the anti-Carcinoembryonic-antigen-related-cell-adhesion-molecule-6 (CEACAM6) antibody DNP002 in patients with advanced solid tumors.

The primary objectives of this study are to evaluate the safety and tolerability of DNP002 in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The secondary objectives are to evaluate the pharmacokinetic properties and preliminary anti-tumor effects in patients with solid tumors. The exploratory objectives are to analyze the expression and relationship with efficacy of various tumor and blood biomarkers.

Eligibility Criteria:
Inclusion Criteria:

1. Male or female patients aged 19 years or older as of the date of written informed consent.
2. Patients with histologically or cytologically confirmed unresectable locally advanced and/or metastatic solid tumors who have been refractory to or had disease progression after standard treatment and have no other available standard treatment options.
3. Patients with at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
4. Patients with an expected survival of greater than or equal to 12 weeks.
5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Patients confirmed to have adequate hematologic, renal, and hepatic function.
7. Patients who have recovered to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or baseline status from reversible side effects of prior anticancer therapies (excluding alopecia \[regardless of grade\] or grade 2 peripheral neuropathy or any laboratory test, blood pressure, and ECG results that meet the inclusion/exclusion criteria).
8. For women of childbearing potential, negative pregnancy test (urine-hCG and/or serum hCG) at the time of clinical trial participation.
9. For women of childbearing potential and men, no plans for pregnancy from screening to 24 weeks after treatment cessation and willingness to use appropriate contraception methods.
10. Voluntary written informed consent for clinical trial participation.

Exclusion Criteria:

1. At the screening visit, you have any of the following comorbidities:

1. Hematologic malignancies, including lymphoma.
2. Interstitial lung disease or pulmonary fibrosis.
3. Bowel obstruction or bowel perforation.
4. Clinically significant pleural effusion, ascites, or pleural effusion.
5. Severe infections or other uncontrolled active infectious diseases requiring treatment with antibiotics, antiviral drugs, etc. that may affect safety and efficacy evaluation during the clinical trial period, as determined by the investigator.
6. Uncontrolled hypertension (systolic blood pressure (SBP) /diastolic blood pressure (DBP) ≥ 160/100 mmHg).
7. QTc interval exceeding 480 msec (same criteria for both sexes) using Fridericia's QT correction formula.
8. Active hepatitis B or C (hepatitis C virus antibody (HCV Ab) positive but HCV ribonucleic acid (RNA) negative may be considered as previous infection and eligible for clinical trial).
9. Clinically significant symptoms or uncontrolled central nervous system (CNS) metastases or carcinomatous meningitis (clinical trial eligibility is possible if no progression has been confirmed clinically and on computed tomography (CT)/magnetic resonance imaging (MRI) for at least 4 weeks prior to the administration of investigational drugs after treatment for CNS or brain metastases and no treatment with steroids or other medications is required at least 2 weeks before administration of investigational drugs).

2. At the screening visit, individuals with the following medical history (including surgical/intervention history):

1. Major surgery or clinically significant traumatic injury within 4 weeks prior to screening
2. Significant cardiovascular disease such as unstable angina, myocardial infarction, congestive heart failure, stroke, or unstable arrhythmia within 24 weeks prior to screening
3. Immunosuppressive disease (e.g., acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV), etc.) or autoimmune disease
4. Psychiatric disorder that, in the opinion of the investigator, significantly affects the clinical trial

3. Subjects who have received the following drug therapies (pharmacological/non-pharmacological):

1. History of immunosuppressive medication within 2 weeks prior to baseline (Day 1 administration date) (Note: Topical, ophthalmic, intra-articular, intranasal, inhaled corticosteroids, and systemic corticosteroids with prednisolone equivalent to 10 mg/day or less are considered exceptions)
2. Other anticancer therapy (excluding investigational medicinal products and immune checkpoint inhibitors) within 3 weeks prior to baseline (Day 1 administration date) (Note: Point radiation for the purpose of relieving symptoms such as bone pain, bronchial obstruction, and skin lesions is allowed, but participation is not allowed if the subject has a history of nitrosoureas or mitomycin-C within 6 weeks prior to baseline)

   \*Radiation (chemo)therapy, chemotherapy, targeted agents (small molecule drugs, monoclonal antibodies), hormonal therapy, etc.
3. History of immune checkpoint inhibitor administration within 4 weeks prior to baseline (Day 1 administration date) (e.g., anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-PD-L2, anti-cluster of differentiation (CD) 137, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), etc.)
4. History of anti-carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 medication within 4 weeks prior to baseline (Day 1 administration date)

4. Subjects with severe hypersensitivity or other immune-related adverse events to monoclonal antibody preparations or the active substance or excipients of DNP002

5. Subjects who participated in other clinical trials and received investigational products (or medical devices) within 4 weeks prior to baseline

6. Other subjects who are deemed ineligible for this clinical trial by the investigator