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

Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05767892
• Other study ID #: SZPH-2023-001
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 1, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2023
• Source: Suzhou Puhe Pharmaceutical Technology Co., LTD
• Contact: Hui Zhao, Doctor
• Phone: +8618911018556
• Email: zh[@]puhebiopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 350
• Est. completion date: December 31, 2026
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Beijing Chest Hospital, Capital Medical University	Beijing	Beijing
China	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University Cancer Hospital	Beijing
China	The First Affiliated Hospital of Bengbu Medical Colleg	Bengbu	Anhui
China	Jilin Provincial Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Third Xiangya Hospital, Central South University	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	Cancer Hospital Affiliated to Guangzhou Medical University	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	Cancer in Zhejiang Province	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Chest Hospital	Hefei	Anhui
China	Anhui Provincial Hospital	Hefei	Anhui
China	Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	Cancer Hospital Affiliated to Shandong First Medical University	Jinan	Shandong
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Affiliated Hospital of Jining Medical University	Jining	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Gansu Provincial Cancer Hospital	Lanzhou	Gansu
China	he First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	he First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Affiliated Hospital of Soochow Universit	Suzhou	Jiangsu
China	Shanxi Cancer Hospital	Taiyuan	Shanxi
China	Taizhou First People's Hospital	Taizhou	Zhejiang
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Yijishan Hospital of Wannan Medical College	Wuhu	Anhui
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	the First Affiliated Hospital; Medical College of Xi'an Jiaotong University	Xian	Shanxi
China	The Second Affiliated Hospital of PLA Air Force Medical University	Xian	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhenzhou	Henan
China	People's Hospital of Zhongshan City	Zhongshan	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Puhe Pharmaceutical Technology Co., LTD

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.