A Multicenter, Open-Label, Dose-Escalation and Dose-Expansion, Phase I Study to Evaluate the Safety, Pharmacokinetics and Anti-tumor Effects of CKD-702 in Patients With Advanced or Metastatic Non-small Cell Lung Cancer Who Failed to Standard Therapy
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Part 1: Maximum Tolerated Dose and/or Recommended Phase 2 Dose
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1(Dose escalation)
Part 1: 3 or 6 subjects are enrolled, per each dose group in a traditional 3+3 design.
Begin with the starting dose determined by the non-clinical study and increase the dose according to the dose levels. If DLT does not occur in the 3 subjects when they have completed the 1st cycle at each dose level, increase the dose to the next level. Dose escalation proceeds until the maximum tolerated dose (MTD) is reached.
Dose-limiting toxicity (DLT) is evaluated following the completion of dosing for the 1st cycle of all subjects enrolled in each dose group in order to determine whether to proceed to the next level. 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).
Intervention: CKD-702 (Drug)
Part 2(Dose expansion)
Part 2: The primary objective of Part 2 is to evaluate the efficacy of CKD-702 by identifying the ORR after administering the RP2D of CKD-702 determined in Part 1. Along with this, to determine the CKD-702 effective patient group, the patient groups were classified into several cohorts based on non-clinical study results.
Therefore, in Part 2, the RP2D determined in Part 1 is administered until the occurrence of an adverse event causing PD occurrence, death or treatment discontinuation, and tumor response is evaluated based on RECIST version 1.1.
Intervention: CKD-702 (Drug)
Outcomes
Primary Outcomes
Part 1: Maximum Tolerated Dose and/or Recommended Phase 2 Dose
Time Frame: 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
Time Frame: Through study completion, an average of 2years
To evaluate the objective response rate(ORR)
Secondary Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Part 2(Dose Expansion): Progression-Free Survival(Through study completion, an average of 3years)
- 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)
- Part 2(Dose Expansion): Overall Survival(Through study completion, an average of 3years)
- Part 2(Dose Expansion): Duration of Response(Through study completion, an average of 3years)
- Part 2(Dose Expansion): Disease Control Rate(Through study completion, an average of 3years)
- 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)
- 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)
- 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,)
- 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)
- 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,)