RC108 plus Furmonertinib as first-line treatment for EGFR-mutated, MET-positive advanced NSCLC

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

This trial tests whether adding RC108 to Furmonertinib works better than Furmonertinib alone for adults with EGFR-mutated, MET-positive unresectable locally advanced or metastatic non-small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: RemeGen Co., Ltd. (Industry-sponsored)
• Drugs / interventions: Furmonertinib, radiation, prednisone
• Locations: 34 sites (Beijing and 33 other locations)
• Trial ID: NCT06962865 on ClinicalTrials.gov

What this trial studies

This is a Phase II interventional trial comparing the combination of RC108 with Furmonertinib against Furmonertinib monotherapy in the first-line setting for patients who have EGFR exon 19 deletion or L858R mutations and are MET-positive. Eligible participants have unresectable locally advanced (stage IIIB/IIIC) or recurrent metastatic (stage IV) NSCLC and measurable disease by RECIST v1.1. The primary focus is on efficacy and safety outcomes, while secondary endpoints include pharmacokinetics and immunogenicity of RC108 when given with Furmonertinib. Participants must provide tumor tissue for testing and meet standard organ function and performance status criteria.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically or cytologically confirmed unresectable locally advanced or recurrent metastatic NSCLC who are EGFR exon 19 deletion or L858R positive, MET-positive, treatment‑naïve to systemic therapy, have ECOG 0–1 and at least one measurable lesion are ideal candidates.

Not a fit: Patients without the specified EGFR mutations or who are MET‑negative, those who have received prior systemic therapy for advanced disease, or those with poor performance status or inadequate organ function are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could improve tumor control and survival compared with Furmonertinib alone for this molecularly defined subgroup.

How similar studies have performed: Other studies combining EGFR tyrosine kinase inhibitors with MET-targeted therapies have shown encouraging activity in MET-driven disease, but first-line combinations in EGFR-mutant, MET-positive patients remain less established.

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;

Where this trial is running

Beijing and 33 other locations

• Beijing Chest Hospital,Capital Medical Unniversity — Beijing, China (Recruiting)
• The Fifth Medical Center of Chinese People's Liberation Army General Hospital — Beijing, China (Recruiting)
• Binzhou Medical University Hospital — Binzhou, China (Recruiting)
• Jilin Cancer Hospital — Changchun, China (Recruiting)
• The Second Xiangya Hospital Of Central South University — Changsha, China (Recruiting)
• Changzhou Cancer Hospital — Changzhou, China (Recruiting)
• Sichuan Cancer Hospital — Chengdu, China (Recruiting)
• West China hospitial of SiChuan University — Chengdu, China (Recruiting)
• Chongqing University Cancer Hospitai — Chongqing, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, China (Recruiting)
• Ganzhou cancer Hospitial — Ganzhou, China (Recruiting)
• Affiliated Cancer Hospital of Guangzhou Medical University — Guangzhou, China (Recruiting)
• The First Affiliated Hospital of Wenzhou Medical University — Guilin, China (Recruiting)
• The Second Affiliated Hospital of Guilin Medical University — Guilin, China (Recruiting)
• Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University — Hangzhou, China (Recruiting)
• Harbin Medical University Cancer Hospital — Harbin, China (Recruiting)
• Anhui Provincial cancer hospital — Hefei, China (Recruiting)
• The First hospitial of Anhui Medicine University — Hefei, China (Recruiting)
• Jinan Central Hospital — Jinan, China (Recruiting)
• Shandong Cancer Hospital — Jinan, China (Recruiting)
• The First hospitial of Lanzhou University — Lanzhou, China (Recruiting)
• Linyi People's Hospital — Linyi, China (Recruiting)
• THE FIRST HOSPITAI OF CHINA MEDICAL UNIVERSITY,No. 155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province — Shenyang, China (Recruiting)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, China (Recruiting)
• Shanxi Cancer Hospital — Taiyuan, China (Recruiting)
• Taizhou hospitial of Zhejiang province — Taizhou, China (Recruiting)
• Tianjin Chest Hospital — Tianjin, China (Recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, China (Recruiting)
• Xiangyang Central Hospital — Xiangyang, China (Recruiting)
• The Second People's Hospital of Yibin City — Yibin, China (Recruiting)
• Yiyang Central Hospital — Yiyang, China (Recruiting)
• Yueyang Central Hospital — Yueyang, China (Recruiting)
• Yunnan Cancer Hospital — Yunnan, China (Recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, China (Recruiting)

Study contacts

• Study coordinator: Heping Liu

Conditions Non-Small Cell Lung Cancer