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A Study of YH25448 in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT04075396

Description:

The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of YH25448 when given orally to participants with epidermal growth factor receptor single activating mutation positive (EGFRm+) locally advanced or metastatic Non Small Cell Lung Cancer (NSCLC).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of YH25448 in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: CR108680
  • SECONDARY ID: 73841937NSC2001
  • SECONDARY ID: YH25448-201
  • NCT ID: NCT04075396

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
YH25448Part D: Outside of Korea

Purpose

The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of YH25448 when given orally to participants with epidermal growth factor receptor single activating mutation positive (EGFRm+) locally advanced or metastatic Non Small Cell Lung Cancer (NSCLC).

Detailed Description

      One-third of all cancer deaths worldwide are still caused by lung cancer and non-small-cell
      lung cancer (NSCLC). YH25448 is an oral, highly potent, mutant-selective and irreversible
      epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKIs) targets both the
      T790M mutation and activating EGFR mutations while sparing wild type-EGFR. The study will be
      conducted in participants with EGFR mutation positive advanced non-small cell lung cancer
      (NSCLC). Study Parts A, B, and C are sponsored by Yuhan Corporation under protocol identifier
      YH25448-201 (ClinicalTrials.gov Identifier: NCT03046992), and Study Part D is sponsored by
      Janssen Research and Development, LLC under protocol identifier 73841937NSC2001. In Part D,
      YH25448 will be given to participants outside Korea, including Caucasians, in order to
      evaluate safety, tolerability, efficacy (including tumor response) and Pharmacokinetics (PK)
      in participants outside of Korea. The duration of this study will be up to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Part D: Outside of KoreaExperimentalParticipants from outside of Korea with progressive disease and on prior epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) therapy will receive recommended phase 2 doses based on safety, tolerability, efficacy and pharmacokinetics (PK) of YH25448.
  • YH25448

Eligibility Criteria

        Inclusion Criteria:

          -  Females should agree to use adequate contraceptive measure, should not be breast
             feeding and must have a negative pregnancy test prior to start of dosing if of
             child-bearing potential or must have evidence of non-child-bearing potential by
             fulfilling one of following criteria at screening; Post-menopausal defined as aged
             more than 50 years and ameorrhoeic for at least 12 months following cessation of all
             exogenous hormonal treatments; Documentation of irreversible surgical sterilization by
             hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal
             ligation; Women under 50 years old would be considered postmenopausal if they have
             been ameorrhoeic for at least 12 months following cessation of exogenous hormonal
             treatment, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone
             (LH) levels in postmenopausal range for the institution

          -  Male participants who have not undergone a vasectomy must agree to use barrier
             contraception that is, condoms, and refrain from donating sperm until 3 months after
             last drug is taken

          -  During the study, and for 3 months after receiving the last dose of study drug, female
             participants must agree not to donate eggs (ova, oocytes) and male participants must
             agree not to donate sperm for the purposes of assisted reproduction

          -  In Part D: Participants outside Korea with histologically or cytologically (that is,
             using pleural effusion, ascites) confirmed Non-Small Cell Lung Cancer (NSCLC) with
             previously diagnosed epidermal growth factor receptor single activating mutation
             positive (EGFRm+), and who have had progressive disease on prior epidermal growth
             factor receptor- Tyrosine kinase inhibitor (EGFR-TKI) therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no
             deterioration over the previous 2 weeks and a minimum life expectancy of 3 months

        Exclusion Criteria:

          -  An unapproved investigational product from another clinical study within 30 days of
             the first dose of study treatment

          -  Treatment with an EGFR TKIs (example: erlotinib or gefitinib) within 8 days or
             approximately 5x half-life, whichever is the longer, of the first dose of study
             treatment or other investigational products within approved indication of marketed
             product (if sufficient wash-out time has not occurred due to schedule or PK
             properties, an alternative appropriate wash-out time based on known duration of time
             to reversibility of drug related adverse events could be agreed upon by sponsor and
             the Investigator)

          -  Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced
             NSCLC from a previous treatment regimen within 14 days of the first dose of study
             treatment - Symtomatic spinal cord compression (if steroid treatment is not required
             within at least 2 weeks prior to the start of the study treatment then the participant
             may be enrolled)

          -  Symtomatic spinal cord compression (if steroid treatment is not required within at
             least 2 weeks prior to the start of the study treatment then the participant may be
             enrolled)

          -  Brain metastases with symptomatic and/or requiring emergency treatment (example;
             Steroid for at least 2 weeks prior to start of study treatment)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part D: Number of Participants with Adverse Event as a Measure of Safety and Tolerability
Time Frame:Up to 2 years
Safety Issue:
Description:An adverse event is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Secondary Outcome Measures

Measure:Part D: Plasma Concentration of YH25448 Metabolites (M6 and M7) After Administration of Single and Multiple Dose
Time Frame:Up to 2 years
Safety Issue:
Description:Plasma Concentration of YH25448 metabolites (M6 and M7) after administration of single and multiple dose will be evaluated.
Measure:Part D: Overall Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants who have at least one confirmed Partial response (PR) or Complete response (CR) (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) prior to disease progression or recurrence. CR is defined when all target lesions (TLs) and non-target lesions (NTLs) present at baseline have disappeared (with the exception of lymph nodes which must be less than (<)10 millimeters (mm) to be considered non-pathological) and no new lesions have developed since baseline. PR is defined when the sum of diameters of the TLs has decreased by 30 percent (%) or more compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions.
Measure:Part D: Duration of Response (DoR)
Time Frame:Up to 2 years
Safety Issue:
Description:DoR is defined as the time from the date of first documented responses until date of documented progression or death whichever comes first.
Measure:Part D: Disease Control Rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description:DCR is defined as the percentage of participants with a best overall, extracranial and intracranial response of CR, PR or Stable Disease (SD). CR is defined as disappearance of all target lesions since baseline. Any pathological lymph nodes selected as target lesions must have a reduction in short axis to < 10 mm. PR is defined as At least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters. SD is defined as Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm for extracranial and intracranial lesion, respectively.
Measure:Part D: Tumor Shrinkage
Time Frame:Up to 2 years
Safety Issue:
Description:Tumor shrinkage is measured at each visit by the percentage change in the sum of the diameters of target lesions compared to baseline measured as greater than or equal to (>=) 10 mm in the longest lesion diameter with computed tomography (CT) or magnetic resonance imaging (MRI).
Measure:Part D: Progression Free Survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:PFS is defined as the time from first dosing date until documented disease progression or death from any cause whichever occur first based on investigator assessment using RECIST 1.1. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm for extracranial and intracranial lesion, respectively.
Measure:Part D: Overall Survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:OS is defined as the interval between the date of first dose and the date of participants death due to any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

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