Clinical trial NCT04667975: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Chong Kun Dang Pharmaceutical
Sponsor class: INDUSTRY
Collaborators: name: Seoul National University Hospital
name: Asan Medical Center
name: Samsung Medical Center
First posted: 2020-12-16
Enrollment: 74
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Maximum Tolerated Dose and/or Recommended Phase 2 Dose
timeFrame: Through study completion, an average of 2years
measure: Part 2: Objective Response Rate
timeFrame: Through study completion, an average of 2years
Secondary outcomes:
measure: Part 1(Dose Escalation): Pharmacokinetics(AUClast of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics( AUCinf of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Cmax of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(t1/2 of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Tmax of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(CL of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Vz of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(MRT of CKD-702 after a single dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(AUClast CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Cmax,ss CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Cmin,ss CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Cav,τ CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(t1/2 CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Tmax,ss CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(CLss CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(Vss CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(MRT CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(accumulation ratio CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Pharmacokinetics(PTF of CKD-702 CKD-702 after a repeated dose)
timeFrame: 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
measure: Part 1(Dose Escalation): Immunogenicity(Analyze the idiotype antibody for hu8C4 (anti-cMET) Fab)
timeFrame: C1D1 Pre-dose, C1D15 Pre-dose, C2D1 Pre-dose, C3D1 Pre-dose, C4D1 Pre-dose,
measure: Part 1(Dose Escalation): Immunogenicity(Analyze the idiotype antibody for Vectibix scFv (anti-EGFR)
timeFrame: C1D1 Pre-dose, C1D15 Pre-dose, C2D1 Pre-dose, C3D1 Pre-dose, C4D1 Pre-dose,
measure: Part 2(Dose Expansion): Overall Survival
timeFrame: Through study completion, an average of 3years
measure: Part 2(Dose Expansion): Progression-Free Survival
timeFrame: Through study completion, an average of 3years
measure: Part 2(Dose Expansion): Duration of Response
timeFrame: Through study completion, an average of 3years
measure: Part 2(Dose Expansion): Disease Control Rate
timeFrame: Through study completion, an average of 3years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Dong-Wan Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: