Clinical trial NCT06962865: A Phase Ⅱ Study of RC108 in Combination With Furmonertinib for the First-line Treatment of EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC
Official title: A Randomized, Open, Controlled, Multicenter Phase II Clinical Study of RC108 in Combination With Furmonertinib Versus Furmonertinib for the First-Line Treatment of EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy and safety of RC108 in combination with Furmonertinib against Furmonertinib for treatment of EGFR mutation combined with MET-positive unresectable locally advanced or recurrent metastatic NSCLC

Detailed description: Primary objective: Evaluate the efficacy and safety of RC108 in combination with Furmonertinib against Furmonertinib for treatment of EGFR mutation combined with MET-positive unresectable locally advanced or recurrent metastatic NSCLC Secondary objective: Evaluate the pharmacokinetic and immunogenicity characteristics of RC108 in combination with Furmonertinib

Eligibility criteria: Inclusion Criteria:

1. Voluntarily participate in the study and signed the ICF;
2. Male or female, aged 18-75 years;
3. All participants to be enrolled must be diagnosed with histopathologically or cytologically confirmed, unresectable locally advanced (stage IIIB/IIIC )or recurrent metastatic NSCLC (stage IV ) and not amendable to curative surgery or radiation as assessed by investigator;
4. For previously locally advanced or recurrent metastatic disease not treated with systemic antitumor therapy;
5. Carring 1 of 2 common EGFR mutations clearly associated with EGFR-TKI sensitivity (i.e., exon 19 deletion or L858R) and MET positivity;
6. Ability to provide at least 6 sections of tumor tissue specimens for staining and testing；
7. ECOG PS score 0 or 1；
8. At least one measurable lesion according to RECIST v1.1 criteria；
9. Expected survival ≥ 12 weeks;
10. Adequate bone marrow and organ function；
11. Female subjects of childbearing potential or male subjects whose partners are of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose, during which time the female subject is not breastfeeding and the male subject avoids sperm donation.

Exclusion Criteria:

1. Subjects with the presence of meningeal metastases, spinal cord compression, or active brain metastases；
2. Received ADC or MET inhibitors；
3. Suffering from refractory nausea and vomiting, chronic gastrointestinal disorders, inability to swallow pharmaceutical preparations, or previous major bowel resection that may prevent adequate absorption, distribution, metabolism, or excretion of oral medications;
4. Subjects with uncontrolled tumor-related pain；
5. Use of an investigational drug or major surgery within 4 weeks before the first dose;
6. Received any live vaccine within 28 days prior to the first dose or plan to be vaccinated during the study;
7. Subjects with uncontrolled or severe cardiovascular disease;
8. Presence of clinically uncontrollable third interstitial effusion;
9. Presence of severe lung disease, including but not limited to active tuberculosis, interstitial lung disease requiring treatment, radiation pneumonitis, etc.
10. Toxicity due to prior antineoplastic therapy has not recovered to National Cancer Institute Commonly Used Criteria Terminology for Generic Adverse Events, Version 5.0, Grade 0-1;
11. Persistent grade ≥2 sensory or motor neuropathy;
12. Active infections requiring systemic IV antibiotic therapy within 7 days before the first dose, allowing routine antimicrobial prophylaxis;
13. Positive test result for Human Immunodeficiency Virus (HIV) or history of Acquired Immune Deficiency Syndrome (AIDS);
14. Active hepatitis B or HCV-positive subjects;
15. Received systemic corticosteroid therapy with \>10 mg/day prednisone or other immunosuppressive medications within 2 weeks before randomization;
16. Other malignant tumor within 5 years before signed the informed consent form;
17. Known hypersensitivity or delayed hypersensitivity to RC108, certain components of Furmonertinib or similar drugs or any contraindication to the drug;
18. Poor compliance and unable to complete the study procedures as assessed by investigator;

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 24 months
measure: Disease Control Rate (DCR)
timeFrame: 24 months
measure: Duration of Response (DoR)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 45 months
measure: Number of participants with adverse events (AEs)
timeFrame: 24 months
measure: Incidence of RC108 anti-drug antibody (ADA)
timeFrame: 24 months
measure: Pharmacokinetic profile of RC108
timeFrame: 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chest Hospital,Capital Medical Unniversity
city: Beijing
country: China
facility: The Fifth Medical Center of Chinese People's Liberation Army General Hospital
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha
country: China
facility: The Second Xiangya Hospital Of Central South University
city: Changzhou
country: China
facility: Changzhou Cancer Hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Chengdu
country: China
facility: West China hospitial of SiChuan University
city: Chongqing
country: China
facility: Chongqing University Cancer Hospitai
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Ganzhou
country: China
facility: Ganzhou cancer Hospitial
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital of Guangzhou Medical University
city: Guilin
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei
country: China
facility: Anhui Provincial cancer hospital
city: Hefei
country: China
facility: The First hospitial of Anhui Medicine University
city: Jinan
country: China
facility: Jinan Central Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Lanzhou
country: China
facility: The First hospitial of Lanzhou University
city: Linyi
country: China
facility: Linyi People's Hospital
city: Shenyang
country: China
facility: THE FIRST HOSPITAI OF CHINA MEDICAL UNIVERSITY,No. 155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
city: Taizhou
country: China
facility: Taizhou hospitial of Zhejiang province
city: Tianjin
country: China
facility: Tianjin Chest Hospital
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
city: Yibin
country: China
facility: The Second People's Hospital of Yibin City
city: Yiyang
country: China
facility: Yiyang Central Hospital
city: Yueyang
country: China
facility: Yueyang Central Hospital
city: Yunnan
country: China
facility: Yunnan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Hunan Cancer Hospital
name: Yongchang Zhang
role: STUDY_DIRECTOR
References: