TRUMP/CTONG1702：NGS指导针对基因变异全覆盖的靶向/免疫治疗中国晚期NSCLC开放、 多中心伞式II 期临床研究

【题目】下一代测序技术指导的针对基因变异全覆盖的靶向/免疫药物治疗中国晚期非小细胞肺癌患者的开放、 多中心伞式II 期临床研究 (TRUMP)
【题目】
1. An Open-label, Multi-center, Phase II Umbrella Study to Assess Efficacy of Targeted Therapy or Immunotherapy Directed by Next Generation Sequencing (NGS) in Chinese Patients With Advanced NSCLC (TRUMP)
2. Phase II Umbrella Study Directed by Next Generation Sequencing (TRUMP)
【注册】NCT03574402  https://clinicaltrials.gov/ct2/show/NCT03574402
【评论】一个令人瞩目，具有开创性的研究！目前快速入组中！


This phase II, umbrella trial study directed by next generation sequencing (NGS) works in Chinese patients with advanced stage NSCLC who never received any anti-tumor treatment. The purpose of this study is to evaluate efficacy of targeted therapies or immunotherapy to NSCLC patients whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug.

Full Title of Study: “An Open-label, Multi-center, Phase II Umbrella Study to Assess Efficacy of Targeted Therapy or Immunotherapy Directed by Next Generation Sequencing (NGS) in Chinese Patients With Advanced NSCLC (TRUMP)”
Study Type

• Study Type: Interventional
• Study Design
  
  
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
    
    
• Study Primary Completion Date: December 30, 2022
  
  

Detailed Description

PRIMARY OBJECTIVES:
I. To evaluate the anti-tumor efficacy of targeted agents or checkpiont inhibitors in advanced stage NSCLC with genomic alteration.
SECONDARY OBJECTIVES:
I. To evaluate the clinical efficacy of targeted agents or checkpiont inhibitors in advanced stage NSCLC with genomic alteration.
II. To evaluate safty and tolerence of targeted agents or checkpiont inhibitors in advanced stage NSCLC with genomic alteration.
Interventions

• Drug: Avitinib Maleate
  
  
  • Patients with EGFR de novo T790m mutation receive Avitinib 300mg orally (PO) twice daily (BID) on day 1-28.
    
    
• Drug: Afatinib
  
  
  • Afatinib will be administered 40mg orally once a day, 28 days as one cycle.
    
    
• Drug: Crizotinib
  
  
  • Patients with MET 14 exon mutation receive crizotinib 250mg PO QD on days 1-28.
    
    
• Drug: X-396
  
  
  • Patients with MET amplification receive ensartinib 225mg PO QD on days 1-28.
    
    
• Drug: Chidamide
  
  
  • Chidamide will be administered 30mg orally twice weekly, 28 days as one cycle.
    
    
  
  

Arms, Groups and Cohorts

• Experimental: Arm1: Avitinib Maleate
  
  
  • Patients with EGFR de novo T790m mutation receive Avitinib 300mg orally (PO) twice daily (BID) on day 1-28.
    
    
• Experimental: Arm2: Chidamide plus Afatinib
  
  
  • Patients with EGFR sensitive mutation with BIM deletion polymorphism receive Afatinib plus Chidamide. Chidamide will be administered 30mg orally twice weekly, 28 days as one cycle. Afatinib will be administered 40mg orally once a day, 28 days as one cycle.
    
    
• Experimental: Arm3: crizotinib
  
  
  • Patients with MET 14 exon mutation receive crizotinib 250mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
    
    
• Experimental: Arm4: X396
  
  
  • Patients with MET amplification receive X396 225mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
    
    
  
  

Clinical Trial Outcome Measures

Primary Measures

• Response rate (RR)
  
  
  • Time Frame: 24 months
  • RECIST version 1.1
    
    
  
  

Secondary Measures

• Progression-free survival (PFS)
  
  
  • Time Frame: 24 months
  • RECIST version 1.1
    
    
• Overall survival (OS)
  
  
  • Time Frame: 48 months
  • Overall Survival is defined as the time from first dose to death due to any cause. Through the follow-up within 30 days after study completion or termination of the last subject, death and date of death will be checked for subject alive during treatment period
    
    
• Duration of response
  
  
  • Time Frame: 24 months
  • RECIST version 1.1
    
    
• Toxicity (number of patients with treatment-related AE as assessed by CTCAE v4.03)
  
  
  • Time Frame: 24 months
  • number of patients with treatment-related AE as assessed by CTCAE v4.03
    
    
  
  

Participating in This Clinical Trial

Inclusion Criteria

1. Histologically or cytologically confirmed, unresectable stage IIIB or stage IV NSCLC 不可手术的IIIB或者IV期非小细胞肺癌一线治疗。
2. Patients who have never received any anticancer treatment regimen Note: Patients that have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease after 12 months from the end of that therapy would be eligible for enrollment.
3. Measurable disease according to RECIST v.1.1 (Irradiated lesions are not considered measurable unless they have clearly progressed since radiotherapy)
4. With or without brain or leptomeningeal metastasis (BM/LM). For patients with symptoms of BM/LM, no need for local therapy should be confirmed by investigator and no dramatic decline of performance status in 2 weeks.
5. ECOG performance status ≤ 2
6. Expected survival > 12 weeks
7. Patients must be suitable and willing to undergo mandatory tumor biopsy according to treating institution's guidelines and requirements for such procedure if there is no archival biopsy available.
8. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures.
EGFR原发T790M突变、EGFR敏感突变+BIM基因缺失多态性、MET14exon突变、MET扩增、ROS1重排、NTRK1/2/3重排、HER2突变、EGFR敏感突变+BM/LM、EGFR 20ins、EGFR扩增……不断增加中……

Exclusion Criteria

1. Active hepatitis (HBsAg positive and HBV copy number in upper limit of normal)
2. Previous or current active interstitial lung disease (ILD)
3. Patients known to be HIV positive or with other acquired, congenital immunodeficiency diseases, or with a medical history of organ transplantation.
4. Major surgery ≤ 2 weeks prior to study entry.
5. Any other malignancies within the last 5 years before study enrollment, except for un completely resected basal cell carcinoma, in situ bladder cancer, cervical carcinoma in situ.
6. Patients previously treated with the investigational drugs or known to be allergic to ingredients or excipients of the investigational drugs.
7. Pregnant or lactating women.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
Investigator Details

• Lead Sponsor
  
  
  • Guangdong Association of Clinical Trials
    
    
• Provider of Information About this Clinical Study
  
  
  • Sponsor
    
    
  
  

【主要研究者】吴一龙
【参加医院和研究者】
1. 广东省人民医院/广东省肺癌研究所  杨衿记 周清
2. 其他医院待明确，有消息者请在本站论坛中提供信息。
【研究执行情况】
接近差不多有18个臂的研究，基本上把晚期非小细胞肺癌全部覆盖了。
【编撰】LAMP
【参考文献】
https://trialbulletin.com/lib/entry/ct-03574402
https://clinicaltrials.gov/ct2/show/NCT03574402

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