RC118 Combined With RC148 as First-Line Treatment for Claudin 18.2-Positive, HER2-Negative Advanced G/GEJ Adenocarcinoma

A Randomized, Controlled, Open-Label, Multicenter Phase II/III Study to Evaluate the Efficacy and Safety of RC118 in Combination With RC148 Versus PD-1 Inhibitor Plus Chemotherapy as First-Line Treatment for Claudin 18.2-Positive, HER2-Negative Locally Advanced Unresectable or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma

This is a randomized, controlled, open-label, multicenter Phase II/III study evaluating the efficacy and safety of RC118 (an antibody-drug conjugate targeting Claudin 18.2) in combination with RC148 versus PD-1 inhibitor (Tislelizumab) plus chemotherapy (CAPOX) as first-line treatment in patients with Claudin 18.2-positive and HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

The study consists of two phases: Phase II will explore the optimal dose combination of RC118 and RC148 across three experimental arms versus a standard comparator arm. Phase III will evaluate the efficacy (progression-free survival) of the recommended Phase III dose (RP3D) combination versus standard of care.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: RC118(Dose 1) plus RC148(Dose 1); Drug: RC118(Dose 1) plus RC148(Dose 2); Drug: RC118(Dose 2) plus RC148(Dose 1); Drug: Tislelizumab Injection plus Oxaliplatin for Injection plus Capecitabine Tablets; Drug: RC118 plus RC148 (phase III); Drug: Tislelizumab Injection plus Oxaliplatin for Injection plus Capecitabine Tablets (phase III)（phase III）

• Study Type: Interventional
• Enrollment (Estimated): 680
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Hongfang Li; Phone Number: 010-65384976; Email: Hongfang.li@remegen.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Cancer Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntarily consent to participate and sign the informed consent form.
2. Age ≥ 18 years.
3. Expected survival > 12 weeks.
4. ECOG performance status of 0 or 1.
5. Histologically confirmed unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma.
6. No prior systemic antitumor therapy for locally advanced or metastatic gastric cancer. If neoadjuvant or adjuvant therapy has been received, disease recurrence or metastasis must occur ≥ 6 months after the end of such therapy.
7. The participant agrees to provide adequate fresh tumor tissue samples or archival paraffin tissue samples collected within the previous 3 years for Claudin 18.2 expression testing. The Claudin 18.2 test result from the central laboratory shows positive Claudin 18.2 expression.
8. Have a local laboratory report confirming HER2 negativity; have a qualified PD-L1 expression test result from a local laboratory or central laboratory.
9. Have at least one measurable lesion per RECIST v1.1.
10. Adequate bone marrow, hepatic and renal function.
11. Male and female participants of reproductive potential must use medically acceptable contraceptive measures from the signing of informed consent until 12 months after the last study treatment. Female participants of reproductive potential must have a negative serum pregnancy test within 7 days before the first dose of study treatment, and agree not to breastfeed or donate oocytes from signing informed consent until 12 months after the last study treatment. Male participants must agree not to donate sperm from signing informed consent until 12 months after the last study treatment.
12. Able to understand the study requirements, and be willing and able to comply with study and follow-up procedures.

Exclusion Criteria:

1. Prior receipt of any antibody drug conjugate, Claudin 18.2 targeted therapy, or concurrent antitumor therapy targeting vascular endothelial growth factor / vascular endothelial growth factor receptor and PD 1/PD L1.
2. Received palliative therapy for localized lesions within 2 weeks prior to randomization, or radiotherapy to the primary gastric lesion within 4 weeks prior to randomization.
3. Received traditional Chinese medicines with antitumor indications, or chemical drugs or biological products with immunomodulatory effects within 2 weeks prior to randomization.
4. Participated in another drug clinical trial and received investigational product within 4 weeks prior to randomization.
5. Underwent major surgery or tumor interventional therapy within 4 weeks prior to randomization, with incomplete recovery, or major surgery anticipated during study treatment.
6. Received live vaccines within 4 weeks prior to randomization or planned to receive any live vaccine during the study.
7. Systemic treatment with corticosteroids or other immunosuppressive agents, either ongoing use or requiring chronic use, within 2 weeks prior to randomization.
8. Presence of leptomeningeal metastasis, spinal cord compression or brainstem metastasis; symptomatic brain metastasis; untreated brain metastasis; symptomatic treatment such as corticosteroids for brain metastasis within 4 weeks prior to randomization; radiotherapy and/or surgery for brain metastasis within 4 weeks prior to randomization; progression of brain metastasis during or after local therapy.
9. Bone metastases with risk of paraplegia.
10. Per CTCAE Version 6.0: peripheral neuropathy ≥ Grade 2; residual toxicity from prior antitumor therapy ≥ Grade 2.
11. Clinically significant bleeding events or bleeding diathesis within 2 months prior to randomization.
12. Severe gastrointestinal dysfunction that may affect drug intake, transit or absorption; significant malnutrition.
13. History of gastrointestinal perforation or fistula, bowel obstruction, inflammatory bowel disease or bowel resection within 6 months prior to randomization.
14. Clinically symptomatic third space effusion requiring intervention within 2 weeks prior to randomization.
15. Active autoimmune disease requiring systemic therapy within 2 years prior to randomization.
16. History of other acquired or congenital immunodeficiency disorders, allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
17. Active or uncontrolled infection within 2 weeks prior to randomization.
18. Severe or inadequately controlled systemic disease.
19. Diagnosis of interstitial lung disease (ILD); or moderate or worse impairment of pulmonary function.
20. History of active or severe cardiac disease.
21. Severe arterial/venous thromboembolic events, or cerebrovascular accidents within 6 months prior to randomization.
22. History of severe coagulopathy, and receiving anticoagulants for therapeutic purposes (prophylactic anticoagulation is excluded).
23. Concurrent second primary malignancy.
24. Hypersensitivity or intolerance to known components of the investigational product or analogous agents.
25. Active infectious disease.
26. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
27. Pregnant or lactating women.
28. Any other disease, metabolic abnormality, abnormal physical finding or laboratory abnormality that raises suspicion of a condition rendering the participant unsuitable for the investigational product, that would confound the interpretation of study results, or that places the participant at substantial risk.
29. Psychiatric disorder, history of substance abuse or social circumstances that may compromise study compliance. Participants judged to have inadequate adherence to this clinical trial, or with other factors making participation inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC118(Dose 1) plus RC148(Dose 1); RC118 and RC148 each have 2 dose levels. This study is designed with 3 arms to screen and confirm the dose.	Drug: RC118(Dose 1) plus RC148(Dose 1); Dose1+Dose1
Experimental: RC118(Dose 1) plus RC148(Dose 2); RC118 and RC148 each have 2 dose levels. This study is designed with 3 arms to screen and confirm the dose.	Drug: RC118(Dose 1) plus RC148(Dose 2); Dose1+Dose2
Experimental: RC118(Dose 2) plus RC148(Dose 1); C118 and RC148 each have 2 dose levels. This study is designed with 3 arms to screen and confirm the dose.	Drug: RC118(Dose 2) plus RC148(Dose 1); Dose2+Dose1
Active Comparator: Tislelizumab+ Oxaliplatin + Capecitabine; Tislelizumab (200 mg Q3W) + Oxaliplatin (130 mg/m² Q3W, max 6 cycles) + Capecitabine (1000 mg/m² BID, D1-14 Q3W)	Drug: Tislelizumab Injection plus Oxaliplatin for Injection plus Capecitabine Tablets; Tislelizumab (200 mg Q3W) + Oxaliplatin (130 mg/m² Q3W, max 6 cycles) + Capecitabine (1000 mg/m² BID, D1-14 Q3W)
Experimental: RC118 plus RC148（phase III）; The dose for Phase III will be determined based on Phase II results.	Drug: RC118 plus RC148 (phase III); The dose for Phase III will be determined based on Phase II results.
Active Comparator: Tislelizumab + Oxaliplatin + Capecitabine (phase III); Tislelizumab (200 mg Q3W) + Oxaliplatin (130 mg/m² Q3W, max 6 cycles) + Capecitabine (1000 mg/m² BID, D1-14 Q3W)	Drug: Tislelizumab Injection plus Oxaliplatin for Injection plus Capecitabine Tablets (phase III)（phase III）; Tislelizumab (200 mg Q3W) + Oxaliplatin (130 mg/m² Q3W, max 6 cycles) + Capecitabine (1000 mg/m² BID, D1-14 Q3W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
（phase II）Objective Response Rate assessed by the investigators according to RECIST v1.1	From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months.
（phase III）Progression-Free Survival assessed by the BIRC according to RECIST v1.1	From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
（phase II/III）Safety	Safety and tolerability as evaluated in terms of incidence of AEs and SAEs	24 months
（phase II/III）OS		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months.
（phase II/III）The incidence of anti-RC118 antibody		24 months
（phase II/III）The incidence of NAbs		24 months
（phase II/III）Describe the plasma concentrations of total antibodies, binding antibodies, free MMAE and RC148 at each time point.		24 months
（phase III）Progression-Free Survival assessed by the investigators according to RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months.
（phase III）ORR assessed by BIRC and investigators per RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months
（phase III）DCR assessed by BIRC and investigators per RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months
（phase III）DoR assessed by BIRC and investigators per RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months
（phase II）DoR assessed by investigators per RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months
（phase II）DCR assessed by investigators per RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months
（phase II）PFS assessed by investigators per RECIST v1.1		From randomization date until disease progression, lost to follow-up, withdrawal of informed consent or death, assessed up to approximately 24 months
（phase II/III）Time to onset of anti-RC118 antibody		24 months
（phase II/III）Duration of anti-RC118 antibody		24 months
（phase II/III）Titer of anti-RC118 antibody		24 months
（phase II/III）The incidence of anti-RC148 antibody		24 months
（phase II/III）Time to onset of anti-RC148 antibody		24 months
（phase II/III）Duration of anti-RC148 antibody		24 months
（phase II/III）Titer of anti-RC148 antibody		24 months
（phase II/III）Area under the plasma concentration-time curve (AUC) of RC118 binding antibodies, free MMAE and RC148.	AUC derived via population pharmacokinetic (PopPK) analysis, if data permit.	24 months
（phase II/III）Time to maximum plasma concentration (Tmax) of RC118 binding antibodies, free MMAE and RC148.	Tmax derived via population pharmacokinetic (PopPK) analysis, if data permit.	24 months
（phase II/III）Maximum observed plasma concentration (Cmax) of RC118 binding antibodies, free MMAE and RC148.	Cmax derived via population pharmacokinetic (PopPK) analysis, if data permit.	24 months
Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Assessed by EORTC QLQ-C30		24 months
Change From Baseline in Gastric Cancer Symptom Scores Assessed by EORTC QLQ-STO22		24 months
Change From Baseline in EQ-5D-5L Health Utility Index Score		24 months
Change From Baseline in EQ-5D Visual Analogue Scale (EQ-VAS) Score		24 months

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: November 1, 2026
• First Submitted That Met QC Criteria: November 8, 2026
• First Posted (Actual): November 13, 2026

Study Record Updates

• Last Update Posted (Actual): November 13, 2026
• Last Update Submitted That Met QC Criteria: November 8, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Care Quality, Access, and Evaluation; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Epidemiologic Methods; Therapeutics; Drug Administration Routes; Drug Therapy; Nucleic Acids, Nucleotides, and Nucleosides; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Epidemiologic Study Characteristics; Clinical Trials as Topic; Clinical Studies as Topic; Capecitabine; Oxaliplatin; Injections; tislelizumab; Clinical Trials, Phase III as Topic
• Other Study ID Numbers: RC118-C301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No