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
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.
| 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). |
| 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 |
| Lead Sponsor | Collaborator |
|---|---|
| Suzhou Puhe Pharmaceutical Technology Co., LTD |
China,
| 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. |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT04129502 -
TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations
|
Phase 3 |