The Purpose of Study is 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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: CKD-702


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Those aged 19 years or older 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. Those whose ECOG performance status is either 0 or 1 Patients who voluntarily decide to participate in this study and provide their written consent. Exclusion Criteria 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) 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) 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 Patients who have tested positive for HIV antibodies Uncontrolled hypertension, diabetes patients 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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1(Dose Escalation) Level 1(10mg/kg) Level 2(15mg/kg) Level 3(20mg/kg) Level 4(25mg/kg) Part 2(Dose Expansion) EGFR TKI resistance EGFR Wild Type
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1(Dose escalation)<br>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). | Drug: CKD-702<br>* In principle, based on 1 cycle of 28 days (4 weeks), administer CKD-702 Inj. once every 2 weeks over 4 weeks.<br>|
| Experimental: Part 2(Dose expansion)<br>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. | Drug: CKD-702<br>* In principle, based on 1 cycle of 28 days (4 weeks), administer CKD-702 Inj. once every 2 weeks over 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum Tolerated Dose and/or Recommended Phase 2 Dose | To determine the maximum tolerated dose (MTD) and/or the recommended phase 2dose (RP2D) | Through study completion, an average of 2years | 
| Part 2: Objective Response Rate | To evaluate the objective response rate(ORR) | Through study completion, an average of 2years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1(Dose Escalation): Pharmacokinetics(AUClast of CKD-702 after a single dose) | 1) 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( AUCinf of CKD-702 after a single dose) | 2) 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) | 3) 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(t1/2 of CKD-702 after a single dose) | 4) 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(Tmax of CKD-702 after a single dose) | 5) 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) | 6) 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(Vz of CKD-702 after a single dose) | 7) 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(MRT of CKD-702 after a single dose) | 8) 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 CKD-702 after a repeated dose) | 9) 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(Cmax,ss CKD-702 after a repeated dose) | 10) 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(Cmin,ss CKD-702 after a repeated dose) | 11) 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(Cav,τ CKD-702 after a repeated dose) | 12) 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(t1/2 CKD-702 after a repeated dose) | 13) 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) | 14) 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(CLss CKD-702 after a repeated dose) | 15) 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(Vss CKD-702 after a repeated dose) | 16) 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 1(Dose Escalation): Pharmacokinetics(MRT CKD-702 after a repeated dose) | 17) 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 1(Dose Escalation): Pharmacokinetics(accumulation ratio CKD-702 after a repeated dose) | 18) 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): Pharmacokinetics(PTF of CKD-702 CKD-702 after a repeated dose) | 19) 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 hu8C4 (anti-cMET) Fab) | -Analyze the idiotype antibody for hu8C4 (anti-cMET) Fab | C1D1 Pre-dose, C1D15 Pre-dose, C2D1 Pre-dose, C3D1 Pre-dose, C4D1 Pre-dose, | 
| Part 1(Dose Escalation): Immunogenicity(Analyze the idiotype antibody for Vectibix scFv (anti-EGFR) | -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 2(Dose Expansion): Overall Survival | To evaluate overall survival (OS) | Through study completion, an average of 3years | 
| Part 2(Dose Expansion): Progression-Free Survival | To evaluate progression-free survival (PFS) | Through study completion, an average of 3years | 
| Part 2(Dose Expansion): Duration of Response | To evaluate the duration of response (DoR) | Through study completion, an average of 3years | 
| Part 2(Dose Expansion): Disease Control Rate | To evaluate the disease control rate (DCR) | Through study completion, an average of 3years |