An Open-label, Dose-finding, Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of DNP002 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- DNP002
- Conditions
- Advanced Solid Tumor
- Sponsor
- Kumho HT Inc.
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Dose-limiting toxicity
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged 19 years or older as of the date of written informed consent.
- •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.
- •Patients with at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Patients with an expected survival of greater than or equal to 12 weeks.
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patients confirmed to have adequate hematologic, renal, and hepatic function.
- •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).
- •For women of childbearing potential, negative pregnancy test (urine-hCG and/or serum hCG) at the time of clinical trial participation.
- •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.
- •Voluntary written informed consent for clinical trial participation.
Exclusion Criteria
- •At the screening visit, you have any of the following comorbidities:
- •Hematologic malignancies, including lymphoma.
- •Interstitial lung disease or pulmonary fibrosis.
- •Bowel obstruction or bowel perforation.
- •Clinically significant pleural effusion, ascites, or pleural effusion.
- •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.
- •Uncontrolled hypertension (systolic blood pressure (SBP) /diastolic blood pressure (DBP) ≥ 160/100 mmHg).
- •QTc interval exceeding 480 msec (same criteria for both sexes) using Fridericia's QT correction formula.
- •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).
- •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).
Arms & Interventions
Participant Group/Arm
Experimental: Patients with advanced solid tumors Dose escalation with patients having solid tumors. Patients receive escalating doses of DNP002 intravenously for 1 hour on Day 1 of each 14-day cycle (Q2W) or each 21-day cycle (Q3W). This course will be repeated in the absence of disease progression or unacceptable toxicity.
Intervention: DNP002
Outcomes
Primary Outcomes
Dose-limiting toxicity
Time Frame: 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).
Characterize the area under the concentration-time curve (AUC) of the pharmacokinetics (PK) of DNP002
Time Frame: 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.
Incidence and severity of treatment emergent adverse events
Time Frame: Up to 2 years
Describe the character and incidence of toxicity based on CTCAE v5.0 that occur receiving DNP002.
Characterize peak plasma concentration (Cmax) of the pharmacokinetics (PK) of DNP002
Time Frame: 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 Outcomes
- Overall response rate (ORR)(Up to 2 years)
- 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.)
- 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.)
- 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.))