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

Sponsor
Suzhou Puhe Pharmaceutical Technology Co., LTD (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05767866
Collaborator
(none)
160
Enrollment
35
Locations
10
Arms
74
Anticipated Duration (Months)
4.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
160 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Preliminary Efficacy of YK-029A, a Novel EGFR TKI, in Patients With Advanced NSCLC Harboring ex20ins, T790M or Rare Mutations
Actual Study Start Date :
Mar 30, 2018
Anticipated Primary Completion Date :
Dec 30, 2023
Anticipated Study Completion Date :
May 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Dose Escalation Component

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
Daily dose of YK-029A
Experimental: Part 2: Expansion Cohort 1

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
Daily dose of YK-029A
Experimental: Part 2: Expansion Cohort 2

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
Daily dose of YK-029A
Experimental: Part 2: Expansion Cohort 3

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
Daily dose of YK-029A
Experimental: Part 3: ExTension Cohort 4

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
Daily dose of YK-029A
Experimental: Part 3: ExTension Cohort 5

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
Daily dose of YK-029A
Experimental: Part 3: ExTension Cohort 6

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
Daily dose of YK-029A
Experimental: Part 3: ExTension Cohort 7

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
Daily dose of YK-029A
Experimental: Part 3: ExTension Cohort 8

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
Daily dose of YK-029A
Experimental: Part 3: ExTension Cohort 9

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
Daily dose of YK-029A

Outcome Measures

Primary Outcome Measures

  1. Part 1: Number of Participants that Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) . [Cycle 1 (Cycle length is equal to [=] 28 days)]

    To investigate the safety and tolerability of YK-029A when given orally to patients with advanced NSCLC with EGFR T790M.

  2. Part 1: Number of Participants with Clinically Significant Abnormal Laboratory Values. [Cycle 1 (Cycle length is equal to [=] 28 days)]

    To investigate the safety and tolerability of YK-029A when given orally to patients with advanced NSCLC with EGFR T790M.

  3. Part 1: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs). [Cycle 1 (Cycle length is equal to [=] 28 days)]

    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.

  4. Part 1: DLTs of Orally Administered YK-029A. [Cycle 1 (Cycle length is equal to [=] 28 days)]

    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.

  5. Part 1: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs). [Cycle 1 (Cycle length is equal to [=] 28 days)]

    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.

  6. Part 1: Maximum Tolerated Dose (MTD) of Orally Administered YK-029A [Cycle 1 (Cycle length is equal to [=] 28 days)]

    The MTD is the highest dose level at which the participant tolerates treatment without dose-limiting toxicities.

  7. Part 2: Objective Response Rate (ORR) according to RECIST 1.1 by IRC [Up to 36 months after first dose]

    Expansion Cohorts 1、2、3 : Confirmed Objective Response Rate (ORR) Assessed by the Independent Review Committee (IRC)

  8. Part 3: Objective Response Rate (ORR) according to RECIST 1.1 by IRC [Up to 36 months after first dose]

    xpansion Cohorts 4、5、6、7、8、9 : Confirmed Objective Response Rate (ORR) Assessed by the Independent Review Committee (IRC)

Secondary Outcome Measures

  1. 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)]

  2. 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]

  3. 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]

  4. 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]

  5. 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.]

  6. 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.]

  7. 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.]

  8. Part2、3：Overall Response Rate (ORR) as Assessed by the investigator. [Up to 36 months after first dose.]

  9. Part2、3：Duration of Response (DOR) [Up to 36 months after first dose.]

    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.

  10. Part2、3：Disease Control Rate (DCR) [Up to 36 months after first dose.]

    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.

  11. Part2、3：Progression Free Survival (PFS) [Up to 36 months after first dose.]

    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.

  12. Part2、3：Overall Survival (OS) [Up to 36 months after first dose.]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. Have gastrointestinal illness or disorder that could affect oral absorption of YK-029A.

  2. 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.

  3. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Anhui Provincial Cancer Hospital Hefei Anhui China 230000
2 Anhui Provincial Hospital Hefei Anhui China 230000
3 The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong China 510000
4 People's Hospital of Guangxi Zhuang Autonomous Region Nanjing Guangxi China 530000
5 Affiliated Tumor Hospital of Guangxi Medical University Nanning Guangxi China 530000
6 Affiliated Cancer Hospital of Harbin Medical University Harbin Heilongjiang China 150000
7 Henan Cancer Hospital Zhengzhou Henan China 450000
8 The First Affiliated Hospital of Zhengzhou University Zhenzhou Henan China 450000
9 Renmin Hospital of Wuhan University Wuhan Hubei China 430000
10 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China 430000
11 Hunan Cancer Hospital Changsha Hunan China 410000
12 Xiangya Hospital Central South University Changsha Hunan China 410000
13 Jiangsu Province Hospital Nanjing Jiangsu China 210000
14 Nanjing Chest Hospital Nanjing Jiangsu China 210000
15 Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University Nanjin Jiangsu China 210000
16 Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu China 221000
17 Xuzhou Central Hospital Xuzhou Jiangsu China 221000
18 Jilin Tumor Hospital Chang chun Jilin China 130000
19 First Hospital of Jilin University Changchun Jilin China 130000
20 Liaoning Cancer Hospital and Institute Shenyang Liaoning China 110000
21 Shengjing Hospital Affiliated to China Medical University Shenyang Liaoning China 110000
22 The First Affiliated Hospital of China Medical University ShenYang Liaoning China 110000
23 Shanxi Cancer Hospital Taiyuan Shanxi China 030000
24 the First Affiliated Hospital; Medical College of Xi'an Jiaotong University Xi'an Shanxi China 710000
25 Tianjin Cancer Hospital Tianjin Tianjin China 300000
26 Cancer in Zhejiang Province Hangzhou Zhejiang China 310000
27 Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou Zhejiang China 310000
28 The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China 325000
29 Peking Union Medical College Hospital Beijing China 10000
30 Beijing Chest Hospital Affiliated to Capital Medical University Beijing China 100102
31 Beijing Hospital Beijing China 100102
32 Beijing Tiantan Hospital affiliated to Capital Medical University Beijing China 100102
33 National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China 100102
34 Peking University Cancer Hospital Beijing China 100102
35 The Fifth Medical Center of the Chinese People's Liberation Army General Hospital Beijing China 100102

Sponsors and Collaborators

  • Suzhou Puhe Pharmaceutical Technology Co., LTD

Investigators

  • Study Director: Hui Zhao, Doctor, Puhe Biopharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Suzhou Puhe Pharmaceutical Technology Co., LTD
ClinicalTrials.gov Identifier:
NCT05767866
Other Study ID Numbers:
  • HNYK-01
First Posted:
Mar 14, 2023
Last Update Posted:
Mar 17, 2023
Last Verified:
Mar 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Suzhou Puhe Pharmaceutical Technology Co., LTD
NSCLC

Study Results

No Results Posted as of Mar 17, 2023