Non-Small Cell Lung Cancer
Conditions
Brief summary
The purpose of study is to evaluate the safety, pharmacokinetics and anti-tumor effects of CKD-702 as a monotherapy and to determine the Recommended Phase 2 Dose(RP2D) in patients with advanced or metastatic non-small cell lung cancer who failed to standard therapy.
Detailed description
This open label, multi center, first-in-human study consists of 2parts. -Part 1: The dose is increased according to the prescribed dose escalation schedule. Dose escalation proceeds until the maximum tolerated dose(MTD) is reached. Dose-limiting toxicity (DLT) is evaluated after completing cycle 1 administration for all subjects enrolled for each dose group in order to determine whether to proceed to the next level. all matters related to dose escalation are subject to the decision of the SRC. If DLT occurs in two subjects during the first dose level process, the dose level reset by the SRC is reflected and study protocol amendment procedure is followed accordingly. Following completion of the DLT evaluation of the planned dose level in this study, the SRC reviews the outcome of the evaluation and determines whether to set additional dosing or proceed to PART 2 (Dose expansion). -Part 2: In Part 2, the recommended phase 2 dose (RP2D) of the CKD-702 Inj. determined in Part 1 is set as the treatment dose, and the dose must be administered with the same administration methods as Part 1, repeating cycles.
Interventions
DRUGCKD-702
In principle, based on 1 cycle of 28 days (4 weeks), administer CKD-702 Inj. once every 2 weeks over 4 weeks.
Sponsors
Seoul National University Hospital
Asan Medical Center
Samsung Medical Center
Chong Kun Dang Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Part 1(Dose Escalation) 1. Level 1(10mg/kg) 2. Level 2(15mg/kg) 3. Level 3(20mg/kg) 4. Level 4(25mg/kg) * Part 2(Dose Expansion) 1. EGFR TKI resistance 2. EGFR Wild Type
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Those aged 19 years or older 2. Patients with a definitive histological or cytological diagnosis of advanced or metastatic non-small-cell lung cancer (NSCLC) (according to the Cancer Staging Manual, AJCC/UICC, 8th ed., IIIB, IIIC and IV) and those for whom there was no applicable standard therapy or the standard therapy failed. 3. Those whose ECOG performance status is either 0 or 1 4. Patients who voluntarily decide to participate in this study and provide their written consent.
Exclusion criteria
1. Patients whose toxicity due to previous anticancer therapy has not been reduced to Grade 1 or lower (However, hair loss of not less than Grade 2 and the peripheral neuropathy of Grade 2 are allowed) 2. Patients with malignant tumors other than NSCLC within the past 3 years of screening (However, treated local basal cell carcinoma or squamous cell carcinoma of skin, carcinoma in situ of uterine cervix, superficial bladder cancer, papillary thyroid carcinoma or, in the opinion of the investigator, malicious tumors that are considered to have little or no recurrence risk within 1 year, are permitted) 3. Patients with a history of serious heart disease such as acute ischemic heart disease within the past 6 months of screening (myocardial infarction, unstable angina, etc.) or heart failure of NYHA Class III or IV 4. Patients who have tested positive for HIV antibodies 5. Uncontrolled hypertension, diabetes patients 6. Patients who have not fully recovered from a major surgery or severe trauma before beginning treatment, or who are expected to undergo a major surgery during the study period or within 6 months of the final dose of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum Tolerated Dose and/or Recommended Phase 2 Dose | Through study completion, an average of 2years | To determine the maximum tolerated dose (MTD) and/or the recommended phase 2dose (RP2D) |
| Part 2: Objective Response Rate | Through study completion, an average of 2years | To evaluate the objective response rate(ORR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1(Dose Escalation): Pharmacokinetics(AUClast of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 1\) AUClast of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics( AUCinf of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 2\) AUCinf of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics(Cmax of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 3\) Cmax of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics(t1/2 of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 4\) t1/2 of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics(Tmax of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 5\) Tmax of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics(MRT of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 8\) MRT of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics(AUClast CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 9\) AUClast CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(Cmax,ss CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 10\) Cmax,ss CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(Cmin,ss CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 11\) Cmin,ss CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(Cav,τ CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 12\) Cav,τ CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(t1/2 CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 13\) t1/2 CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(CL of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 6\) CL of CKD-702 after a single dose |
| Part 1(Dose Escalation): Pharmacokinetics(CLss CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 15\) CLss CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(Vss CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 16\) Vss CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(MRT CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 17\) MRT CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(accumulation ratio CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 18\) accumulation ratio CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(PTF of CKD-702 CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 19\) PTF of CKD-702 CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Immunogenicity(Analyze the idiotype antibody for hu8C4 (anti-cMET) Fab) | C1D1 Pre-dose, C1D15 Pre-dose, C2D1 Pre-dose, C3D1 Pre-dose, C4D1 Pre-dose, | -Analyze the idiotype antibody for hu8C4 (anti-cMET) Fab |
| Part 1(Dose Escalation): Immunogenicity(Analyze the idiotype antibody for Vectibix scFv (anti-EGFR) | C1D1 Pre-dose, C1D15 Pre-dose, C2D1 Pre-dose, C3D1 Pre-dose, C4D1 Pre-dose, | -Analyze the idiotype antibody for Vectibix scFv (anti-EGFR) |
| Part 2(Dose Expansion): Overall Survival | Through study completion, an average of 3years | To evaluate overall survival (OS) |
| Part 2(Dose Expansion): Progression-Free Survival | Through study completion, an average of 3years | To evaluate progression-free survival (PFS) |
| Part 2(Dose Expansion): Duration of Response | Through study completion, an average of 3years | To evaluate the duration of response (DoR) |
| Part 2(Dose Expansion): Disease Control Rate | Through study completion, an average of 3years | To evaluate the disease control rate (DCR) |
| Part 1(Dose Escalation): Pharmacokinetics(Tmax,ss CKD-702 after a repeated dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 14\) Tmax,ss CKD-702 after a repeated dose |
| Part 1(Dose Escalation): Pharmacokinetics(Vz of CKD-702 after a single dose) | C1D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs, C2D1 Pre-dose, Start of Infusion 0.5, 1hr, End of Infusion and End of Infusion 2, 6, 22, 70, 166, 336hrs | 7\) Vz of CKD-702 after a single dose |
Countries
South Korea
Contacts
Primary ContactKeehyun Ham
Outcome results
None listed