Assessing an Oral EGFR Inhibitor,YK-209A in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR

Treatment Clinical Trial

Official title:

Safety and Preliminary Efficacy of YK-029A, a Novel EGFR TKI, in Patients With Advanced NSCLC Harboring ex20ins, T790M or Rare Mutations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05767866
• Other study ID #: HNYK-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Treatment
• Treatment Side Effects

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.