Advanced Solid Tumor
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDNP002
Anti-CEACAM6 monoclonal antibody
Sponsors
Kumho HT Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize peak plasma concentration (Cmax) of the pharmacokinetics (PK) of DNP002 | Day 1 (pre-dose), 1 hour (post-dose), 2, 4, 8 10, 12 hours, Day 2, Day 3, Day 8 after 1st or 5th doses of the investigational drug. | Samples for pharmacokinetic evaluation will be collected immediately prior to each of the 5 doses, and at predetermined time intervals after the 1st and 5th doses. |
| Dose-limiting toxicity | Up to 2 or 3 weeks | DLT is assessed according to NCI-CTCAE v5.0. The assessment is conducted only in the 2-week interval for subjects receiving the first dose (2-week interval subject) or the 3-week interval for subjects receiving the first dose (3-week interval subject). |
| Incidence and severity of treatment emergent adverse events | Up to 2 years | Describe the character and incidence of toxicity based on CTCAE v5.0 that occur receiving DNP002. |
| Characterize the area under the concentration-time curve (AUC) of the pharmacokinetics (PK) of DNP002 | Day 1 (pre-dose), 1 hour (post-dose), 2, 4, 8 10, 12 hours, Day 2, Day 3, Day 8 after 1st or 5th doses of the investigational drug. | Samples for pharmacokinetic evaluation will be collected immediately prior to each of the 5 doses, and at predetermined time intervals after the 1st and 5th doses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Up to 2 years | Percentage of patients whose best response to DNP002 is either a Complete response or Partial response, both defined according to RECIST or iRECIST criteria respectively. |
| Leukocyte immune phenotyping | Day 1 (pre-dose), before the first, third, and fifth doses of the investigational drug, as well as 24 hours after the first and fifth doses. | Whole blood flow cytometry analysis for characterization of blood leukocyte/lymphocyte including MDSC with regards to subpopulation and activation before and under treatment in all patients. |
| Serum biomarkers | Day 1 (pre-dose), before the first, third, and fifth doses of the investigational drug, as well as 4 hours after the first and fifth doses. | Total concentration of Arginase-1, soluble CEACAM6, CEA, Interferon-gamma and Interleukin-6 in serum derived from whole blood taken before and under treatment in all patients. |
| Concentration of anti-drug antibodies | Prior to administration at each dose (The investigational drug should be continued with dosing every two weeks as long as there is no disease progression or unacceptable toxicity.) | Concentration in plasma |
Countries
South Korea
Contacts
Primary ContactMoonki Choi, M.D., Ph.D.
Outcome results
None listed