RC48 Combined With Adebrelimab, Apatinib and S-1 as Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Disitamab Vedotin Combined With Adebrelimab, Apatinib and S-1 as Neoadjuvant Therapy in Locally Advanced Gastric Cancer With HER2 Overexpression: a Prospective, Phase II Study

This study is a prospective, open-label, phase II clinical trial that aims to enroll patients with locally advanced gastric adenocarcinoma who have not received any prior treatment and are candidates for surgery. The study drugs include RC48, Adebrelimab, Apatinib and S-1. The purpose is to evaluate the effectiveness and safety of the combined coordinated treatment of multi-mechanism drugs for perioperative treatment of locally advanced gastric cancer with HER2 overexpression.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer/Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: RC48; Drug: Adebrelimab; Drug: Apatinib; Drug: S-1

Detailed Description

The study plans to enroll 32 subjects. After signing the informed consent form and meeting the inclusion and exclusion criteria, patients will receive standard-dose treatment of the RC48, Adebrelimab, Apatinib and S-1 regimen for 3-4 cycles (every 3 weeks) before surgery. Apatinib will only be used for 14 days in the last cycle. Imaging studies will be conducted 3-4 weeks after the last dose to assess the efficacy of neoadjuvant therapy and the possibility of radical D2 gastrectomy. The treatment plan after curative surgery for gastric cancer will be determined by the investigators and the patients based on the pathological findings. Patients who benefit clinically after surgery may receive adjuvant therapy with RC48, Adebrelimab, Apatinib and S-1 for 4 cycles (the first treatment is expected to start around 4 weeks after surgery) or follow the standard postoperative adjuvant regimen recommended by the guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaofeng Chen, Ph.D; Phone Number: 13585172066; Email: chenxiaofengnjmu@163.com
• Study Contact Backup: Name: Hao Xu, Ph.D; Phone Number: 13851530117; Email: 66881866@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Participants voluntarily join this study, are able to complete the signing of the informed consent form, and have good compliance;
• 2. Age between 18 to 75 years old (at the time of signing the informed consent form), with no gender restrictions;
• 3. Gastrointestinal cancer or gastroesophageal junction adenocarcinoma confirmed by histology and/or cytology, diagnosed as locally advanced according to the 8th edition of the AJCC standards, with a cTNM diagnosis of T3-4aN+M0 and T4aNanyM0 based on ultrasound endoscopy or enhanced CT/MRI scan (and diagnostic laparoscopy if necessary), and agree to receive curative surgical treatment, with the investigator assessing the potential for tumor resectability;
• 4. Have not previously received systemic treatment for the current disease, including anti-tumor chemotherapy/immunotherapy, etc.;
• 5. HER2 overexpression confirmed by IHC results from endoscopic biopsy tissue (defined as: IHC 2+, 3+);
• 6. ECOG score of 0-1;
• 7. Estimated life expectancy of ≥6 months;
• 8. Good major organ function:

Exclusion Criteria:

• 1. Concurrent malignant disease other than gastric cancer (excluding early-stage tumors that have been radically treated);
• 2. Tumor lesions with a tendency to bleed (such as active ulcerative tumor lesions with positive fecal occult blood test, history of hematemesis or melena within 2 months before signing the informed consent form, or assessed by the investigator as being at risk of significant gastrointestinal hemorrhage, etc.) or having received blood transfusion treatment within 4 weeks before the study medication; 3. Inability to take oral medication;
• 4. Currently participating in another interventional clinical study treatment, or having received other investigational drugs or used investigational medical devices within 4 weeks before the first administration of the study medication;
• 5. Has had systemic treatment required within 2 years before the first administration of the study medication;
• 6. Known allogeneic organ transplantation (except for corneal transplantation);
• 7. Known allergy to any medication used in this study;
• 8. Peripheral neuropathy of grade ≥2;
• 9. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibodies);
• 10. Active hepatitis B or C infection;
• 11. Received live vaccines within 30 days before the first administration (Day 1 of Cycle 1);
• 12. Pregnant or breastfeeding women;
• 13. Presence of any severe or uncontrollable systemic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental; RC48, Adebrelimab, Apatinib and S-1 regimen for 3-4 cycles (every 3 weeks) before surgery.

Drug: RC48; RC48: 2.5 mg/kg, intravenous infusion, on day 1, every 3 weeks (Q3W); Other Names: Disitamab Vedotin; Drug: Adebrelimab; Adebrelimab：1200 mg, intravenous infusion, on day 1, every 3 weeks (Q3W); Drug: Apatinib; Apatinib: 250mg, oral administration, once daily (qd), every 3 weeks (Q3W); Drug: S-1; S-1：For patients with a body surface area (BSA) ≤1.5m², use 50mg each time; for patients with BSA >1.5m², use 60mg each time, oral administration, twice daily (bid), on days 1-14, every 3 weeks (Q3W); Other Names: S-1tegafur, gimeracil and oteracil potassium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response Rate (pCR)	Defined as the proportion of subjects with no residual viable tumor cells on microscopy and negative lymph nodes out of the total number of subjects;	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response rate (MPR)	Defined as the proportion of subjects with ≤10% viable tumor cells in the resected specimen out of the total number of subjects;	4 months
R0 Resection rate	Complete tumor resection during surgery with negative microscopic margins, meaning no residual tumor;	4 months
Disease-Free Survival (DFS）	Defined as the time from enrollment to the first radiological evidence of disease recurrence or death (whichever occurs first)	24 months
Overall Survival (OS)	Defined as the time from enrollment to the subject's death from any cause	36 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Xiaofeng Xiaofeng, Ph.D, The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Hao Xu, Ph.D, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Immunoconjugates; Apatinib; Tegafur; Disitamab vedotin
• Other Study ID Numbers: 2024-SR-233

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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