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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05767866
Other study ID # HNYK-01
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date March 30, 2018
Est. completion date May 30, 2024

Study information

Verified date March 2023
Source Suzhou Puhe Pharmaceutical Technology Co., LTD
Contact Hui Zhao, Doctor
Phone +8618911018556
Email zh@puhebiopharma.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study aimed to evaluate the safety and preliminary efficacy of YK-029A, a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in treated or untreated patients with advanced non-small cell lung cancer (NSCLC).


Description:

This phase 1/2 study will evaluate the safety, pharmacokinetics, and anti-tumor activity of oral EGFR Inhibitor YK-209A in participants with NSCLC and anti-tumor activity of YK-029A in participants with solid tumors other than NSCLC harboring ex20ins, T790M or rare mutations. The trial will be conducted in three parts: a dose escalation (Part 1), expansion phase (Part 2), followed by an extension phase (Part 3). The objectives of the dose escalation phase (Part 1), is to determine the safety profile of orally administered YK-029A, including the MTD, DLTs, RP2D, pharmacokinetic profile. The primary goal of the expansion component of the trial is to evaluate the anti-tumor activity of YK-029A in nine histologically and molecularly defined cohorts at the RP2D (determined based on dose escalation phase of the trial).


Recruitment information / eligibility

Status Recruiting
Enrollment 160
Est. completion date May 30, 2024
Est. primary completion date December 30, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: General Inclusion Criteria all cohorts: dose escalation, dose expansion, and dose extension: 1. Have histologically or cytologically confirmed locally advanced or metastatic NSCLC disease (Stage IIIB or IV) . 2. Male or femal adult,be able to provide a signed and dated, written informed consent. 3. Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1. 4. Minimum life expectancy of 3 months or more. 5. Adequate organ function at baseline. 6. Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected (Fridericia) (QTcF) of less than or equal to (= ) 450 millisecond (ms) in males or = 470 ms in females. Part 1: Dose Escalation Cohort Specific Inclusion Criteria: 1. Refractory to standard available therapies. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. 3. aged 18-65 years old. 4. previously treated NSCLC patients with EGFR T790M. Part 2: Expansion Cohort 1?2?3 Specific Inclusion Criteria: 1. previously treated NSCLC patients with EGFR T790M. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 3. aged 18-75 years old. Part 2: Expansion Cohort 4?5 Specific Inclusion Criteria: 1. previously treated NSCLC patients with EGFR exton 20ins. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 3. aged 18-75 years old. Part 3: Expansion Cohort 6 Specific Inclusion Criteria: 1. previously untreated NSCLC patients with EGFR exton 20ins. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 3. aged 18-75 years old. Part 3: Expansion Cohort 7?8 Specific Inclusion Criteria: 1. previously treated NSCLC patients with EGFR rare mutation((G719X?L861Q?S768I). 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 3. aged 18-75 years old. Part 3: Expansion Cohort9 Specific Inclusion Criteria: 1. previously treated NSCLC patients with EGFR exton 20ins. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 3. aged 18-75 years old. Exclusion Criteria: 1. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before screening. 2. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose or with a wide field of radiation which must be completed within 4 weeks before screening. 3. NSCLC patients with EGFR T790M mutation previously treated with third-generation EGFR-TKIs (such as AZD9291, CO-1686, HM61713, EGF816, PF-06747775, vometinib, BPI-15086, Ivirtinib maleate, etc.) and their apis or the same drugs in other clinical trials Drug treatment. 4. Patients with NSCLC with EGFR ex20ins mutation had previously received EGFR ex20ins inhibitors and/or EGFR-cMET double antibodies (including but not limited to TAK-788, bociotinib, JNJ-61186372, DZD9008, vometinib, PLB1004, and AZD9291 in excess of the clinically approved dose (cohort 9 prohibited AZD9291 at any dose) and Drug substance or other similar drug treatment in the clinical trial stage. 5. NSCLC patients with rare EGFR mutations have previously been treated with third-generation EGFR-Tkis (such as AZD9291, etc.) and their apis or other similar drugs in clinical trials. 6. Received a moderate or strong CYP4503A inhibitor or moderate or strong CYP3A inducer within 10 days prior to first dose of YK-029A. 7. Have significant, uncontrolled, or active cardiovascular disease. 8. Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure. 9. Have prolonged QTcF interval, or being treated with medications known to be associated with the development of torsades de pointes. 10. Have an ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics, or a known history of human immunodeficiency virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of history. 11. Currently have or have a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis. 12. Female participants who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period. Note: Female participants who are lactating will be eligible if they discontinue breastfeeding. 13. Have gastrointestinal illness or disorder that could affect oral absorption of YK-029A. 14. Have any condition or illness that, in the opinion of the investigator, might compromise participant safety or interfere with the evaluation of the safety of the drug. 15. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
YK-029A
Daily dose of YK-029A

Locations

Country Name City State
China Beijing Chest Hospital Affiliated to Capital Medical University Beijing
China Beijing Hospital Beijing
China Beijing Tiantan Hospital affiliated to Capital Medical University Beijing
China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing
China Peking Union Medical College Hospital Beijing
China Peking University Cancer Hospital Beijing
China The Fifth Medical Center of the Chinese People's Liberation Army General Hospital Beijing
China Jilin Tumor Hospital Chang chun Jilin
China First Hospital of Jilin University Changchun Jilin
China Hunan Cancer Hospital Changsha Hunan
China Xiangya Hospital Central South University Changsha Hunan
China The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong
China Cancer in Zhejiang Province Hangzhou Zhejiang
China Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou Zhejiang
China Affiliated Cancer Hospital of Harbin Medical University Harbin Heilongjiang
China Anhui Provincial Cancer Hospital Hefei Anhui
China Anhui Provincial Hospital Hefei Anhui
China Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University Nanjin Jiangsu
China Jiangsu Province Hospital Nanjing Jiangsu
China Nanjing Chest Hospital Nanjing Jiangsu
China People's Hospital of Guangxi Zhuang Autonomous Region Nanjing Guangxi
China Affiliated Tumor Hospital of Guangxi Medical University Nanning Guangxi
China Liaoning Cancer Hospital and Institute Shenyang Liaoning
China Shengjing Hospital Affiliated to China Medical University Shenyang Liaoning
China The First Affiliated Hospital of China Medical University ShenYang Liaoning
China Shanxi Cancer Hospital Taiyuan Shanxi
China Tianjin Cancer Hospital Tianjin Tianjin
China The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang
China Renmin Hospital of Wuhan University Wuhan Hubei
China Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei
China the First Affiliated Hospital; Medical College of Xi'an Jiaotong University Xi'an Shanxi
China Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu
China Xuzhou Central Hospital Xuzhou Jiangsu
China Henan Cancer Hospital Zhengzhou Henan
China The First Affiliated Hospital of Zhengzhou University Zhenzhou Henan

Sponsors (1)

Lead Sponsor Collaborator
Suzhou Puhe Pharmaceutical Technology Co., LTD

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part 1: Number of Participants that Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) . To investigate the safety and tolerability of YK-029A when given orally to patients with advanced NSCLC with EGFR T790M. Cycle 1 (Cycle length is equal to [=] 28 days)
Primary Part 1: Number of Participants with Clinically Significant Abnormal Laboratory Values. To investigate the safety and tolerability of YK-029A when given orally to patients with advanced NSCLC with EGFR T790M. Cycle 1 (Cycle length is equal to [=] 28 days)
Primary Part 1: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs). To establish Maximum Tolerated Dose (MTD) (if possible) and Recommended Phase 2 Dose (PR2D) of YK-029A when given orally in patients with advanced NSCLC with EGFR T790M mutations. Cycle 1 (Cycle length is equal to [=] 28 days)
Primary Part 1: DLTs of Orally Administered YK-029A. Toxicity will be Evaluated According to the NCI CTCAE, Version 5.00. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications. Cycle 1 (Cycle length is equal to [=] 28 days)
Primary Part 1: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs). Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.00. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications. Cycle 1 (Cycle length is equal to [=] 28 days)
Primary Part 1: Maximum Tolerated Dose (MTD) of Orally Administered YK-029A The MTD is the highest dose level at which the participant tolerates treatment without dose-limiting toxicities. Cycle 1 (Cycle length is equal to [=] 28 days)
Primary Part 2: Objective Response Rate (ORR) according to RECIST 1.1 by IRC Expansion Cohorts 1?2?3 : Confirmed Objective Response Rate (ORR) Assessed by the Independent Review Committee (IRC) Up to 36 months after first dose
Primary Part 3: Objective Response Rate (ORR) according to RECIST 1.1 by IRC xpansion Cohorts 4?5?6?7?8?9 : Confirmed Objective Response Rate (ORR) Assessed by the Independent Review Committee (IRC) Up to 36 months after first dose
Secondary Part 1:Cmax: Maximum Plasma Concentration for YK-029A and its Active Metabolites after a Single Oral Dose. Up to 24 hours; Pre-dose and multiple time points post-dose on Cycle 1 Day 1 (C1D1)
Secondary Part1:Tmax: Time to Cmax for YK-029A and its Active Metabolites after a Single Oral Dose. Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1
Secondary Part1:AUC24: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 hours for YK-029A and its Active Metabolites after a Single Oral Dose Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1
Secondary Part1:AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration for YK-029A and its Active Metabolites after a Single Oral Dose. Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1
Secondary Part1:Cmax, ss: Maximum Plasma Concentration for YK-029A and its Active Metabolites at Steady State after Multiple Oral Doses. Up to approximately 168 days; Pre-dose and multiple time points post-dose.
Secondary Part1:Tmax, ss: Time to Cmax for YK-029A and its Active Metabolites at Steady State after Multiple Oral Doses. Up to approximately 168 days; Pre-dose and multiple time points post-dose.
Secondary AUC24, ss: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 hours for YK-029A and its Active Metabolites at Steady State after Multiple Oral Doses. Up to approximately 168 days; Pre-dose and multiple time points post-dose.
Secondary Part2?3:Overall Response Rate (ORR) as Assessed by the investigator. Up to 36 months after first dose.
Secondary Part2?3:Duration of Response (DOR) Duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that PD is objectively documented. Up to 36 months after first dose.
Secondary Part2?3:Disease Control Rate (DCR) DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 42 days) after the initiation of study drug. Up to 36 months after first dose.
Secondary Part2?3:Progression Free Survival (PFS) PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST version 1.1 are met or death, whichever occurs first. Up to 36 months after first dose.
Secondary Part2?3:Overall Survival (OS) OS is defined as the interval from the date of randomization until death. OS is defined as the interval from the date of randomization until death. OS is defined as the interval from the date of randomization until death. Up to 36 months after first dose.
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