YK-029A as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations

A Randomized Phase 3 Multicenter Open-Label Study to Compare the Efficacy of YK-029A as First-Line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations

The purpose of this study is to compare the effectiveness of YK-029A as first-line treatment with that of platinum-based chemotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors has epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

Participants will be randomly assigned to one of the two treatment groups YK-029A group or Platinum-based chemotherapy group.

Participants will receive YK-029A orally and pemetrexed/cisplatin or pemetrexed/carboplatin via vein until the participants experience worsening disease (PD) as assessed by blinded independent review committee (IRC), intolerable harmful effects or another discontinuation criteria.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: YK-209A tablet; Drug: Pemetrexed+carboplatin/Cisplatin

Detailed Description

The drug being tested in this study is called YK-029A. YK-029A is being tested to evaluate the efficacy as a first line treatment compare with platinum-based chemotherapy in the participants with locally advanced or NSCLC whose tumors harbor EGFR exon 20 insertion mutations.

The study will enroll 350 patients. Participants will be randomly assigned to one of the two treatment groups-YK-029A Group (Arm A) or Platinum-based Chemotherapy Group (Arm B).

The participants will be administered with YK-029A orally in arm A and pemetrexed/cisplatin or pemetrexed/carboplatin intravenously (IV) in arm B until the participants experience progressive disease (PD) as assessed by blinded independent review committee (IRC), intolerable toxicity or another discontinuation criteria.

Participants in the chemotherapy group should not be allowed to cross over to treatment with YK-029A after IRC-assessed PD is documented. Randomized treatment with YK-029A or platinum-based chemotherapy may be continued after PD, at the discretion of the investigator and with the sponsor's approval, if there is still evidence of clinical benefit.

This multi-center trial will be conducted in China . The overall time to participate in this study is until 3 years after the last participant is randomized. Participants will make multiple visits to the clinic and will be followed for survival, subsequent anticancer therapy, subsequent disease assessment outcome until disease progression on a subsequent anticancer therapy, and participant-reported health status (EORTC QLQ-C30 and EORTC QLQ-LC13) for 3 years after the last participant is randomized in the study and 30 days after the last dose of study drug for safety follow-up.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hui Zhao, Doctor; Phone Number: +8618911018556; Email: zh@puhebiopharma.com

Study Locations

• China
  • Beijing, China, 10000
    • Peking Union Medical College Hospital
  • Beijing, China, 100102
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Principal Investigator: Jie Wang, Doctor
    • Sub-Investigator: Chunjian Duan, Doctor
  • Beijing, China, 100102
    • Peking University Cancer Hospital
    • Contact: Jun Zhao, Doctor
  • Anhui
    • Bengbu, Anhui, China, 233000
      • The First Affiliated Hospital of Bengbu Medical Colleg
      • Contact: Chenling Zhao
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Chest Hospital
      • Contact: XuHong Min
    • Wuhu, Anhui, China, 241000
      • Yijishan Hospital of Wannan Medical College
      • Contact: Zhiwei Lu
  • Beijing
    • Beijing, Beijing, China, 100102
      • Beijing Chest Hospital, Capital Medical University
      • Contact: Zhe Liu
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • The Second Affiliated Hospital of Chongqing Medical University
      • Contact: Zhengzhou Yang
    • Chongqing, Chongqing, China, 400000
      • The First Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Provincial Cancer Hospital
      • Contact: Yunjian Huang
    • Xiamen, Fujian, China, 361000
      • The first affiliated hospital of xiamen university
      • Contact: Jinxun Wu
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Gansu Provincial Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
      • Contact: Minhui Wang
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
    • Guangzhou, Guangdong, China, 510080
      • Cancer Hospital Affiliated to Guangzhou Medical University
      • Contact: Chuan Jing
    • Zhongshan, Guangdong, China, 528400
      • People's Hospital of Zhongshan City
      • Contact: Jiewen Peng
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guizhou Provincial People's Hospital
      • Contact: Xianwei Ye
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Fourth Hospital of Hebei Medical University
      • Contact: Yudong Wang
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin medical university cancer hospital
      • Contact: Baogang Liu
  • Henan
    • Luoyang, Henan, China, 471000
      • he First Affiliated Hospital of Henan University of Science and Technology
      • Contact: Yeye Zhang
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
    • Zhenzhou, Henan, China, 450000
      • The first affiliated hospital of Zhengzhou university
      • Contact: Xingya Li
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Xiaorong Tong
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Qian Chu
  • Hunan
    • Changsha, Hunan, China, 410000
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410000
      • Third Xiangya Hospital, Central South University
      • Contact: Xuewen Liu
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 010000
      • Affiliated Hospital of Inner Mongolia Medical University
      • Contact: Junzhen Gao
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Province Hospital
      • Contact: Renhua Guo
    • Suzhou, Jiangsu, China, 215000
      • The Second Affiliated Hospital of Soochow Universit
      • Contact: Zhixiang Zhuang
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • The Second Affiliated Hospital of Nanchang University
      • Contact: Xiaoqun Ye
    • Nanchang, Jiangxi, China, 330000
      • The First Affiliated Hospital of NanChang University
      • Contact: Longhua Sun
    • Nanchang, Jiangxi, China, l330000
      • Jiangxi Cancer Hospital
      • Contact: Hui Luo
  • Jilin
    • Changchun, Jilin, China, 130000
      • Jilin Provincial Cancer Hospital
      • Contact: Yin Chen
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • he First Affiliated Hospital of China Medical University
      • Contact: Mingfang Zhao
  • Shandong
    • Jinan, Shandong, China, 250000
      • Qilu Hospital of Shandong University
      • Contact: Lian Liu
    • Jinan, Shandong, China, 250000
      • Cancer Hospital Affiliated to Shandong First Medical University
      • Contact: Haiyong Wang
    • Jining, Shandong, China, 272000
      • Affiliated Hospital of Jining Medical University
      • Contact: Shuchen Ye
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University
      • Contact: Helei Lou
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Shanghai Pulmonary Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Cancer Hospital
    • Xian, Shanxi, China, 710000
      • the First Affiliated Hospital; Medical College of Xi'an Jiaotong University
      • Contact: Yu Y
    • Xian, Shanxi, China, 710000
      • The Second Affiliated Hospital of PLA Air Force Medical University
      • Contact: Haichuan Su
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Provincial People's Hospital
      • Contact: Ke Xie
    • Chengdu, Sichuan, China, 610000
      • West China Hospital, Sichuan University
      • Contact: Dan Liu
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Tianjin cancer hospital
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Contact: Y Fang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Jianya Zhou
    • Hangzhou, Zhejiang, China, 310000
      • Cancer in Zhejiang Province
      • Contact: Yun Fan
    • Taizhou, Zhejiang, China, 318000
      • Taizhou Hospital of Zhejiang Province
      • Contact: Youzu Xu
    • Taizhou, Zhejiang, China, 318000
      • Taizhou First People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female adult patients (aged 18 years or older).
2. Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC.
3. Documented epidermal growth factor receptor (EGFR) in-frame exon 20 insertion mutation assessed by a clinical laboratory improvements amendment (CLIA)-certified (China sites) or an accredited (outside of the US) local laboratory.

3、The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or human epidermal growth factor receptor 2 (HER2) mutations except EGFR mutations for which there are approved anti-EGFR tyrosine kinase inhibitors [TKIs] (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid).

4、Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR exon 20 insertion mutation.

5、At least 1 measurable lesion per RECIST Version 1.1. 6、Life expectancy ≥3 months. 7、Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 8、Adequate organ and hematologic function as defined by blood transfusions with a recommended >/ 14 day washout period.

Exclusion Criteria:

1. Received prior systemic treatment for locally advanced or metastatic disease, including local administration, such as intra-pleural injection of anticancer medication with the exception noted below.
2. Neoadjuvant or adjuvant chemotherapy/immune therapy for Stage I to III or combined modality chemotherapy/radiation for locally advanced disease is allowed if completed >6 months before the development of metastatic disease.
3. Received radiotherapy ≤14 days before randomization or has not recovered from radiotherapy-related toxicities.
4. Received a moderate or strong cytochrome P450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 10 days before first dose of YK-029A.
5. Concurrent EGFR mutations: exon 19 deletion, L858R, T790M, G719X, S768I, or L861Q.
6. Have been diagnosed with another primary malignancy other than NSCLC。
7. Have current spinal cord compression or leptomeningeal disease.
8. Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
9. Received a live vaccine within 4 weeks before randomization per Summary of product characteristics (SmPCs) for pemetrexed, cisplatin, and carboplatin.
10. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses (i.e., hemophilia and Von Willebrand disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YK-029A Group (Arm A)	Drug: YK-209A tablet; YK-029A 200 milligram (mg) , orally without food，once daily until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria.
Active Comparator: Platinum-based Chemotherapy Group (Arm B)	Drug: Pemetrexed+carboplatin/Cisplatin; Participants randomized into chemotherapy arm can receive up to 6 cycles of pemetrexed + carboplatin (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve 5 mg/ml per minute (AUC5), IV infusion, every 3 weeks) as the initial treatment. Participants whose disease has not progressed after 4 cycles of first-line platinum-based doublet chemotherapy may receive pemetrexed maintenance monotherapy until a treatment discontinuation criterion is met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) as Assessed by Blinded Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 .	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 approximately 36 months after the first participant is randomized.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1	Confirmed ORR is defined as the percentage of participants who are confirmed to have achieved complete response (CR) or partial response (PR). Confirmed responses are responses that persist on repeat imaging ≥4 weeks after initial response.	Up to approximately 36 months after the first participant is randomized.
Overall Survival (OS)	OS is defined as the interval from the date of randomization until death.	Up to approximately 36 months after the first participant is randomized.
Progression Free Survival (PFS) as Assessed by the Investigator	PFS is defined as the time interval from the date of randomization until the first date at which the criteria for PD according to RECIST Version 1.1 are met or death, whichever occurs first.	Up to approximately 36 months after the first participant is randomized.
Confirmed Objective Response Rate (ORR) as Assessed by the Investigator	Confirmed ORR is defined as the percentage of participants who are confirmed to have achieved CR or PR. Confirmed responses are responses that persist on repeat imaging ≥4 weeks after initial response.	Up to approximately 36 months after the first participant is randomized.
Duration of Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator.	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 or death (whichever occurs first) is objectively documented.	Up to approximately 36 months after the first participant is randomized.
Disease Control Rate (DCR) as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator	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 6 weeks) after the initiation of study drug.	Up to approximately 36 months after the first participant is randomized.
Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30	EORTC QLQ-C30 is a cancer-specific questionnaire which comprises of 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); and a global health status/quality-of-life (QoL) scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Raw scores will be converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QoL scale, higher scores represent better HRQoL, whereas for the symptom scales lower scores represent better HRQoL (i.e., a low level of symptomatology/problems).	Up to approximately 36 months after the first participant is randomized.
Participant-reported Symptoms as Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, Lung Cancer Module (QLQ-LC13).	EORTC QLQ-LC13 is a cancer-specific questionnaire which comprises of 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Raw scores will be converted into scale scores ranging from 0 to 100. Higher scores represent a high level of symptomatology/problems.	Up to approximately 36 months after the first participant is randomized.

Collaborators and Investigators

• Sponsor: Suzhou Puhe Pharmaceutical Technology Co., LTD
• Investigators: Study Director: Hui Zhao, Doctor, Puhe Biopharma

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): July 30, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 11, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; EGFR; EXON 20ins
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: SZPH-2023-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No