Clinical trial NCT05767892: YK-029A as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
Keywords: NSCLC
EGFR
EXON 20ins
Lead sponsor: Suzhou Puhe Pharmaceutical Technology Co., LTD
Sponsor class: INDUSTRY
First posted: 2023-03-14
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Blinded Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 .
timeFrame: Up to approximately 36 months after the first participant is randomized.
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: Overall Survival (OS)
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: Progression Free Survival (PFS) as Assessed by the Investigator
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: Duration of Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator.
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: Disease Control Rate (DCR) as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: 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
timeFrame: Up to approximately 36 months after the first participant is randomized.
measure: 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).
timeFrame: Up to approximately 36 months after the first participant is randomized.
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical Colleg
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Chest Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Cancer Hospital Affiliated to Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Zhongshan
country: China
facility: People's Hospital of Zhongshan City
state: Guangdong
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: he First Affiliated Hospital of Henan University of Science and Technology
state: Henan
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: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
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: Third Xiangya Hospital, Central South University
state: Hunan
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow Universit
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Provincial Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: he First Affiliated Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Cancer Hospital Affiliated to Shandong First Medical University
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xian
country: China
facility: the First Affiliated Hospital; Medical College of Xi'an Jiaotong University
state: Shanxi
city: Xian
country: China
facility: The Second Affiliated Hospital of PLA Air Force Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
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: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou First People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Beijing
country: China
facility: Peking Union Medical College Hospital
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
Study officials:
affiliation: Puhe Biopharma
name: Hui Zhao, Doctor
role: STUDY_DIRECTOR
References: