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 (CKD-702)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: CKD-702

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 Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Keehyun Ham; Phone Number: 82-2-6373-0916; Email: hamki@ckdpharm.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Dong-Wan Kim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	Drug: CKD-702; In principle, based on 1 cycle of 28 days (4 weeks), administer CKD-702 Inj. once every 2 weeks over 4 weeks.
EXPERIMENTAL: 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.	Drug: CKD-702; In principle, based on 1 cycle of 28 days (4 weeks), administer CKD-702 Inj. once every 2 weeks over 4 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Collaborators: Samsung Medical Center; Asan Medical Center; Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 21, 2020
• Primary Completion (ANTICIPATED): August 15, 2021
• Study Completion (ANTICIPATED): August 30, 2024

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (ACTUAL): December 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 187NSCLC18021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No