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

NCT05767866 | Unknown Phase 1 DMC

• 1 other identifier: HNYK-01
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 35

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).

Conditions

Treatment; Treatment Side Effects

Keywords

NSCLC

Outcome Measures

Primary Outcomes (8)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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

• 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 Outcomes (12)

• 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)

• 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

• 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

• 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

• 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.

Study Arms (10)

Part 1: Dose Escalation Component

EXPERIMENTAL

In dose-escalation phase, previously treated patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 50, 100, 150, 200 to 250 mg/day (3+3 design).

Drug: YK-029A

Part 2: Expansion Cohort 1

EXPERIMENTAL

In dose-escalation phase, previously treated patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 50mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 2: Expansion Cohort 2

EXPERIMENTAL

In dose-escalation phase, previously treated patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 100mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 2: Expansion Cohort 3

EXPERIMENTAL

In dose-escalation phase, previously treated patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 150mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 3: ExTension Cohort 4

EXPERIMENTAL

In dose-extension phase, previously treated patients with EGFR exon 20ins mutation were enrolled. YK-029A was given at doses of 150mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 3: ExTension Cohort 5

EXPERIMENTAL

In dose-extension phase, previously treated patients with EGFR exon 20ins mutation were enrolled. YK-029A was given at doses of 200mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 3: ExTension Cohort 6

EXPERIMENTAL

In dose-extension phase, previously untreated patients with EGFR exon 20ins mutation were enrolled. YK-029A was given at doses of 200mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 3: ExTension Cohort 7

EXPERIMENTAL

In dose-extension phase, previously treated patients with EGFR rare mutation （G719X、L861Q、S768I etal.)were enrolled. YK-029A was given at doses of 150mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 3: ExTension Cohort 8

EXPERIMENTAL

In dose-extension phase, previously treated patients with EGFR rare mutation （G719X、L861Q、S768I etal.)were enrolled. YK-029A was given at doses of 200mg/day and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Part 3: ExTension Cohort 9

EXPERIMENTAL

In dose-extension phase, previously untreated patients with EGFR exon 20ins mutation were enrolled. YK-029A was given at doses of 150mgBID and who have no active, measurable central nervous system (CNS) metastases.

Drug: YK-029A

Interventions

YK-029A DRUG

Daily dose of YK-029A

Part 1: Dose Escalation Component; Part 2: Expansion Cohort 1; Part 2: Expansion Cohort 2; Part 2: Expansion Cohort 3; Part 3: ExTension Cohort 4; Part 3: ExTension Cohort 5; Part 3: ExTension Cohort 6; Part 3: ExTension Cohort 7; Part 3: ExTension Cohort 8; Part 3: ExTension Cohort 9

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: 18-75 Years and older (Adult, Older Adult)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically or cytologically confirmed locally advanced or metastatic NSCLC disease (Stage IIIB or IV) .
• Male or femal adult，be able to provide a signed and dated, written informed consent.
• Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1.
• Minimum life expectancy of 3 months or more.
• Adequate organ function at baseline.
• 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.
• Refractory to standard available therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• aged 18-65 years old.
• previously treated NSCLC patients with EGFR T790M.
• previously treated NSCLC patients with EGFR T790M.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• aged 18-75 years old.
• previously treated NSCLC patients with EGFR exton 20ins.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

You may not qualify if:

• Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before screening.
• 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.
• 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.
• 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.
• 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.
• Received a moderate or strong CYP4503A inhibitor or moderate or strong CYP3A inducer within 10 days prior to first dose of YK-029A.
• Have significant, uncontrolled, or active cardiovascular disease.
• Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
• Have prolonged QTcF interval, or being treated with medications known to be associated with the development of torsades de pointes.
• 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.
• Currently have or have a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis.
• 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.
• Have gastrointestinal illness or disorder that could affect oral absorption of YK-029A.
• 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.

Sponsors & Collaborators

• Suzhou Puhe Pharmaceutical Technology Co., LTD: lead

Study Sites (35)

Anhui Provincial Cancer Hospital

Hefei, Anhui, 230000, China

RECRUITING

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510000, China

RECRUITING

People's Hospital of Guangxi Zhuang Autonomous Region

Nanjing, Guangxi, 530000, China

RECRUITING

Affiliated Tumor Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

RECRUITING

Affiliated Cancer Hospital of Harbin Medical University

Harbin, Heilongjiang, 150000, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhenzhou, Henan, 450000, China

RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430000, China

RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410000, China

RECRUITING

Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University

Nanjin, Jiangsu, 210000, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Nanjing Chest Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, 221000, China

RECRUITING

First Hospital of Jilin University

Changchun, Jilin, 130000, China

RECRUITING

Jilin Tumor Hospital

Changchun, Jilin, 130000, China

RECRUITING

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, 110000, China

RECRUITING

Shengjing Hospital Affiliated to China Medical University

Shenyang, Liaoning, 110000, China

RECRUITING

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, 110000, China

RECRUITING

Shanxi Cancer Hospital

Taiyuan, Shanxi, 030000, China

RECRUITING

the First Affiliated Hospital; Medical College of Xi'an Jiaotong University

Xi’an, Shanxi, 710000, China

RECRUITING

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 300000, China

RECRUITING

Cancer in Zhejiang Province

Hangzhou, Zhejiang, 310000, China

RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

RECRUITING

Peking Union Medical College Hospital

Beijing, 10000, China

RECRUITING

Beijing Chest Hospital Affiliated to Capital Medical University

Beijing, 100102, China

RECRUITING

Beijing Hospital

Beijing, 100102, China

RECRUITING

Beijing Tiantan Hospital affiliated to Capital Medical University

Beijing, 100102, China

RECRUITING

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, 100102, China

RECRUITING

Peking University Cancer Hospital

Beijing, 100102, China

RECRUITING

The Fifth Medical Center of the Chinese People's Liberation Army General Hospital

Beijing, 100102, China

RECRUITING

Related Publications (1)

• Duan J, Wu L, Yang K, Zhao J, Zhao Y, Dai X, Li M, Xie Y, Yao Y, Zhao M, Zhou C, Ren X, Liu Z, Pan Y, Li Y, Liu B, Cheng Y, Miao L, Yu Q, Zhang Z, Liu X, Cui J, Zhang Y, Zhang L, Li X, Li X, Shen B, Chen B, Zeng S, Li B, Hu Y, Li L, Wu R, Song Q, Wang J. Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial. J Thorac Oncol. 2024 Feb;19(2):314-324. doi: 10.1016/j.jtho.2023.09.1449. Epub 2023 Sep 28.

  PMID: 37776953 DERIVED

Study Officials

• Hui Zhao, Doctor

  Puhe Biopharma

  STUDY DIRECTOR

Central Study Contacts

Hui Zhao, Doctor

CONTACT

+8618911018556; zh@puhebiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 14, 2023
• Study Start: March 30, 2018
• Primary Completion: December 30, 2023
• Study Completion: May 30, 2024
• Last Updated: March 17, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (35)