SHR-1701 + Rivoceranib (± SHR-2554) in Advanced GC After First-Line Immunotherapy Failure

NCT07311408 | Recruiting Phase 2

• 2 other identifiers: MA-GC-II-029will be entered later
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the efficacy of SHR-1701 combined with Rivoceranib, with or without SHR-2554, in patients with gastric or gastroesophageal junction adenocarcinoma who have progressed on or were intolerant to first-line immunotherapy-containing treatment

Conditions

Gastric Cancer (GC); Gastroesophageal Junction Adenocarcinoma

Keywords

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; Rivoceranib; Failed First-Line Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  To evaluate the efficacy of anti-tumor by Resist1.1 (In months)

  From the date of first treatment until the date of first documented disease progression (assessed per RECIST 1.1) or death from any cause, whichever occurs first, assessed up to 24 months.

Secondary Outcomes (4)

• Objective response rate (ORR)

  From the start of treatment until the first occurrence of documented complete response (CR) or partial response (PR) per RECIST 1.1, assessed up to 24 month

• Disease control rate (DCR)

  From the start of treatment until the first documented complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1, assessed up to 24 months.

• Overall survival (OS)

  From the date of first treatment until the date of death from any cause, assessed up to 36 months

• Safety

  From the first dose of study treatment until 30 days after the last dose, assessed up to approximately 26 months.

Other Outcomes (1)

• Multi-omics analysis of the tumor microenvironment

  From enrollment to the end of the study

Study Arms (2)

SHR-1701+Rivoceranib + SHR-2554

EXPERIMENTAL

Drug: SHR-1701 Administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. The infusion time should be controlled between 30 and 60 minutes, and must not exceed 2 hours. Drug: Rivoceranib Administered orally (PO) once daily (QD), continuously. Administration Instructions: To be taken orally with warm water, approximately 30 minutes after a meal. The daily dosing time should be consistent. Drug: SHR-2554 Administered orally (PO) twice daily (BID). Administration Instructions: Can be taken before or after meals, but administration approximately 30 minutes after morning and evening meals is recommended. The daily dosing times should be consistent.

Drug: SHR-1701 + Rivoceranib

SHR-1701 + Rivoceranib.

ACTIVE COMPARATOR

Drug: SHR-1701 Administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. The infusion time should be controlled between 30 and 60 minutes, and must not exceed 2 hours. Drug: Rivoceranib Administered orally (PO) once daily (QD), continuously. Administration Instructions: To be taken orally with warm water, approximately 30 minutes after a meal. The daily dosing time should be consistent.

Drug: SHR-1701+Rivoceranib + SHR-2554

Interventions

SHR-1701 + Rivoceranib DRUG

Drug: SHR-1701 Administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. The infusion time should be controlled between 30 and 60 minutes, and must not exceed 2 hours. Drug: Rivoceranib Administered orally (PO) once daily (QD), continuously. Administration Instructions: To be taken orally with warm water, approximately 30 minutes after a meal. The daily dosing time should be consistent.

SHR-1701+Rivoceranib + SHR-2554

SHR-1701+Rivoceranib + SHR-2554 DRUG

Drug: SHR-1701 Administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. The infusion time should be controlled between 30 and 60 minutes, and must not exceed 2 hours. Drug: Rivoceranib Administered orally (PO) once daily (QD), continuously. Administration Instructions: To be taken orally with warm water, approximately 30 minutes after a meal. The daily dosing time should be consistent. Drug: SHR-2554 Administered orally (PO) twice daily (BID). Administration Instructions: Can be taken before or after meals, but administration approximately 30 minutes after morning and evening meals is recommended. The daily dosing times should be consistent.

SHR-1701 + Rivoceranib.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, male or female.
• Histologically or pathologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
• Disease progression on or intolerance to a prior treatment regimen that contained an immune checkpoint inhibitor (ICI).
• HER2-negative expression.
• Willingness to provide tumor tissue samples from prior to the first systemic therapy for biomarker analysis (e.g., PD-L1). Freshly obtained biopsies are preferred; if unavailable, archived formalin-fixed paraffin-embedded (FFPE) tissue blocks or 5-8 slides of 3-5μm thickness are acceptable.
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function, defined as:
• Hemoglobin ≥ 90 g/L (no blood transfusion within 14 days);
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
• Platelet count ≥ 90 × 10\^9/L;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN;
• Serum creatinine ≤ 1.5 × ULN;

You may not qualify if:

• Gastrointestinal perforation and/or fistula within 6 months prior to treatment, or active gastrointestinal bleeding within 3 months.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Known history of allergy to any component of the investigational drugs or their excipients.
• Prior treatments as follows:
• Treatment with any other investigational agent within 4 weeks prior to the first dose of the study drug, or within 5 half-lives of the previous investigational agent (whichever is longer).
• Concurrent enrollment in another interventional clinical study. (Observation studies or follow-up phases of interventional studies are permitted).
• Any antitumor therapy (including radiotherapy, chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biotherapy, or tumor embolization) within 2 weeks prior to the first dose of the study drug.
• Requirement for systemic corticosteroids (\>10 mg prednisone equivalent daily) within 2 weeks prior to the first dose. The use of corticosteroids for premedication with certain chemotherapy regimens, inhaled or topical steroids, and adrenal replacement therapy at doses ≤10 mg/day prednisone equivalent is permitted. Other cases require discussion with the Investigator.
• Prior administration of an anti-tumor vaccine or live vaccine within 4 weeks prior to the first dose.
• Major surgery or significant trauma within 4 weeks prior to the first dose.
• History of leptomeningeal metastasis, or current evidence of leptomeningeal metastasis or active brain metastases. (Patients with stable, treated brain metastases may be discussed for eligibility).
• Active autoimmune disease or history of autoimmune disease requiring systemic treatment in the past 2 years. Exceptions include vitiligo, resolved childhood asthma/atopy, hypothyroidism stable on hormone replacement, or Type I diabetes stable on insulin regimen.
• Immunodeficiency history, including positive HIV test, other acquired/congenital immunodeficiency disorders, history of organ transplant or allogeneic bone marrow transplantation, or active hepatitis.
• Poorly controlled cardiovascular diseases, including but not limited to: (1) Heart failure of NYHA Class II or higher; (2) Unstable angina; (3) Myocardial infarction within the past year; (4) Clinically significant supraventricular or ventricular arrhythmia without effective medical control.
• Severe infection within 4 weeks prior to the first dose. Active pulmonary inflammation on baseline imaging, or signs/symptoms of active infection within 2 weeks prior to the first dose.

Sponsors & Collaborators

• Jingdong Zhang: lead

Study Sites (1)

Liaoning Provincial Cancer Hospital

Shenyang, Liaoning, 11000, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

SHR-1701; apatinib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Qian Dong, Doctor

CONTACT

17309815028; dongqian08@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Professor

Study Record Dates

• First Submitted: November 30, 2025
• First Posted: December 31, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 31, 2025

Record last verified: 2025-11

Locations

CN (1)