Clinical trial NCT05767866: Assessing an Oral EGFR Inhibitor,YK-209A in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR
Official title: Safety and Preliminary Efficacy of YK-029A, a Novel EGFR TKI, in Patients With Advanced NSCLC Harboring ex20ins, T790M or Rare Mutations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Treatment
Treatment Side Effects
Keywords: NSCLC
Lead sponsor: Suzhou Puhe Pharmaceutical Technology Co., LTD
Sponsor class: INDUSTRY
First posted: 2023-03-14
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants that Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) .
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 1: Number of Participants with Clinically Significant Abnormal Laboratory Values.
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 1: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs).
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 1: DLTs of Orally Administered YK-029A.
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 1: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs).
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 1: Maximum Tolerated Dose (MTD) of Orally Administered YK-029A
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 2: Objective Response Rate (ORR) according to RECIST 1.1 by IRC
timeFrame: Up to 36 months after first dose
measure: Part 3: Objective Response Rate (ORR) according to RECIST 1.1 by IRC
timeFrame: Up to 36 months after first dose
Secondary outcomes:
measure: Part 1:Cmax: Maximum Plasma Concentration for YK-029A and its Active Metabolites after a Single Oral Dose.
timeFrame: Up to 24 hours; Pre-dose and multiple time points post-dose on Cycle 1 Day 1 (C1D1)
measure: Part1:Tmax: Time to Cmax for YK-029A and its Active Metabolites after a Single Oral Dose.
timeFrame: Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1
measure: 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
timeFrame: Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1
measure: 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.
timeFrame: Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1
measure: Part1:Cmax, ss: Maximum Plasma Concentration for YK-029A and its Active Metabolites at Steady State after Multiple Oral Doses.
timeFrame: Up to approximately 168 days; Pre-dose and multiple time points post-dose.
measure: Part1:Tmax, ss: Time to Cmax for YK-029A and its Active Metabolites at Steady State after Multiple Oral Doses.
timeFrame: Up to approximately 168 days; Pre-dose and multiple time points post-dose.
measure: 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.
timeFrame: Up to approximately 168 days; Pre-dose and multiple time points post-dose.
measure: Part2、3：Overall Response Rate (ORR) as Assessed by the investigator.
timeFrame: Up to 36 months after first dose.
measure: Part2、3：Duration of Response (DOR)
timeFrame: Up to 36 months after first dose.
measure: Part2、3：Disease Control Rate (DCR)
timeFrame: Up to 36 months after first dose.
measure: Part2、3：Progression Free Survival (PFS)
timeFrame: Up to 36 months after first dose.
measure: Part2、3：Overall Survival (OS)
timeFrame: Up to 36 months after first dose.
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Nanjing
country: China
facility: People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Nanning
country: China
facility: Affiliated Tumor Hospital of Guangxi Medical University
state: Guangxi
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhenzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Chest Hospital
state: Jiangsu
city: Nanjin
country: China
facility: Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Chang chun
country: China
facility: Jilin Tumor Hospital
state: Jilin
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated to China Medical University
state: Liaoning
city: ShenYang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: the First Affiliated Hospital; Medical College of Xi'an Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Cancer in Zhejiang Province
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital Affiliated to Capital Medical University
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Tiantan Hospital affiliated to Capital Medical University
city: Beijing
country: China
facility: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
city: Beijing
country: China
facility: Peking University Cancer Hospital
city: Beijing
country: China
facility: The Fifth Medical Center of the Chinese People's Liberation Army General Hospital
Study officials:
affiliation: Puhe Biopharma
name: Hui Zhao, Doctor
role: STUDY_DIRECTOR
References: