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

Phase 2

Not yet recruiting

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: RC108 plus Furmonertinib Mesilate Tablets; Drug: Furmonertinib Mesilate Tablets Monotherapy

• Registration Number: NCT06962865
• Lead Sponsor: RemeGen Co., Ltd.

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

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-30
• Study First Submitted QC: 2025-04-30
• Last Update Submitted: 2025-04-30
• Study First Posted: 2025-05-08
• Last Update Posted: 2025-05-08
• Study Start: 2025-06-15
• Primary Completion: 2026-05-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	RC108 plus Furmonertinib Mesilate Tablets	1L, EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC
Arm 2	Furmonertinib Mesilate Tablets Monotherapy	1L, EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	24 months	Investigator-assessed ORR

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs)	24 months	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Incidence of RC108 anti-drug antibody (ADA)	24 months	Incidence, occurrence time and ADA titer of positive RC108 ADA and neutralizing antibodies
Pharmacokinetic profile of RC108	24 months	Peak and trough concentrations of RC108 total antibody (TAb), conjugated antibody (ADC), free MMAE
Progression-free survival (PFS)	24 months	Investigator-assessed PFS
Disease Control Rate (DCR)	24 months	Investigator-assessed DCR
Duration of Response (DoR)	24 months	Investigator-assessed DoR
Overall survival (OS)	45 months	Investigator-assessed OS

Trial Locations

Locations (26)

Binzhou Medical University Hospital; 🇨🇳 Binzhou, China

The Second Xiangya Hospital Of Central South University; 🇨🇳 Changsha, China

Changzhou Cancer Hospital; 🇨🇳 Changzhou, China

Sichuan Cancer Hospital; 🇨🇳 Chengdu, China

West China hospitial of SiChuan University; 🇨🇳 Chengdu, China

Chongqing University Cancer Hospitial; 🇨🇳 Chongqing, China

Fujian Cancer Hospital; 🇨🇳 Fuzhou, China

Ganzhou cancer Hospitial; 🇨🇳 Ganzhou, China

The First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 Guilin, China

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, China

Anhui Provincial cancer hospital; 🇨🇳 Hefei, China

The First hospitial of Anhui Medicine University; 🇨🇳 Hefei, China

Jinan Central Hospital; 🇨🇳 Jinan, China

Shandong Cancer Hospital; 🇨🇳 Jinan, China

The First hospitial of Lanzhou University; 🇨🇳 Lanzhou, China

Linyi People's Hospital; 🇨🇳 Linyi, China

Nanyang Second General Hospital; 🇨🇳 Nanyang, China

ZhongShan Hospital Fudan University; 🇨🇳 Shanghai, China

Shanxi Cancer Hospital; 🇨🇳 Taiyuan, China

Taizhou hospitial of Zhejiang province; 🇨🇳 Taizhou, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, China

Xiangyang Central Hospital; 🇨🇳 Xiangyang, China

The Second People's Hospital of Yibin City; 🇨🇳 Yibin, China

Yiyang Central Hospital; 🇨🇳 Yiyang, China

Yueyang Central Hospital; 🇨🇳 Yueyang, China