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

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StatusVrbovanje

Sponzori

Janssen Research & Development, LLC

Suradnici

Yuhan Corporation

KLINIČKO ISPITIVANJE: NCT04075396

BioSeek: nct04075396

Ključne riječi

Sažetak

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).

Opis

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. Study treatment should be held in all participants with suspected (symptomatic) or documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive disease, until recovery from all infection related symptoms, and documented to be negative for SARS-CoV-2.

Datumi

Posljednja provjera:	06/30/2020
Prvo podneseno:	08/20/2019
Predviđena prijava poslana:	08/28/2019
Prvo objavljeno:	08/29/2019
Posljednje ažuriranje poslano:	07/08/2020
Posljednje ažuriranje objavljeno:	07/12/2020
Stvarni datum početka studija:	10/15/2019
Procijenjeni datum primarnog završetka:	07/31/2021
Procijenjeni datum završetka studije:	08/16/2021

Stanje ili bolest

Carcinoma, Non-Small-Cell Lung

Intervencija / liječenje

Drug: Part D: Outside of Korea

Faza

Faza 1/Faza 2

Grupe ruku

Ruka	Intervencija / liječenje
Experimental: Part D: Outside of Korea Participants 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.	Drug: Part D: Outside of Korea Participants will receive YH25448 tablets once daily.

Kriterij prihvatljivosti

Dobni uvjeti za studiranje	20 Years Do 20 Years
Spolovi koji ispunjavaju uvjete za studij	All
Prihvaća zdrave volontere	Da
Kriteriji	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)

Ishod

Primarne mjere ishoda

1. Part D: Number of Participants with Adverse Event as a Measure of Safety and Tolerability [Up to 2 years]

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.

2. Part D: Plasma Concentration of YH25448 After Administration of Single Dose (SD) [Up to 2 years]

Plasma Concentration of YH25448 after administration of single dose will be evaluated.

3. Part D: Plasma Concentration of YH25448 After Administration of Multiple Dose (MD) [Up to 2 years]

Plasma Concentration of YH25448 after administration of multiple dose will be evaluated.

Sekundarne mjere ishoda

1. Part D: Plasma Concentration of YH25448 Metabolites (M6 and M7) After Administration of Single and Multiple Dose [Up to 2 years]

Plasma Concentration of YH25448 metabolites (M6 and M7) after administration of single and multiple dose will be evaluated.

2. Part D: Overall Response Rate (ORR) [Up to 2 years]

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.

3. Part D: Duration of Response (DoR) [Up to 2 years]

DoR is defined as the time from the date of first documented responses until date of documented progression or death whichever comes first.

4. Part D: Disease Control Rate (DCR) [Up to 2 years]

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.

5. Part D: Tumor Shrinkage [Up to 2 years]

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).

6. Part D: Progression Free Survival (PFS) [Up to 2 years]

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.

7. Part D: Overall Survival (OS) [Up to 2 years]

OS is defined as the interval between the date of first dose and the date of participants death due to any cause.