Fruquintinib Combined With PD-1 Inhibitor and FOLFOX as First-Line Treatment For Advanced Gastric Cancer

Fruquintinib Combined With Tislelizumab and FOLFOX as First-Line Treatment For Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-center, Open-label, Phase Ib/II Clinical Study

This study was designed to explore the efficacy and safety of fruquintinib combined with tislelizumab and FOLFOX regimen as the first treatment (first-line) for adults diagnosed with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; PD-1 Inhibitor; Fruquintinib; Gastric (Stomach) Cancer; GEJ Adenocarcinoma; Tislelizumab
• Intervention / Treatment: Drug: fruquintinib + tislelizumab + FOLFOX

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiaohui Zhai; Phone Number: 862038285497; Email: zhaixh@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 210000
      • The Sixth Affiliated Hospital of Sun Yat-sen University
      • Principal Investigator: Yanhong Deng
      • Contact: Xiaohui Zhai; Phone Number: 862038285497; Email: zhaixh@mail.sysu.edu.cn
      • Sub-Investigator: Xiaohui Zhai

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-75 years old (including 18 and 75 years old);
• Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
• Pathologically determined gastric or gastroesophageal junction adenocarcinoma;
• Advanced patients with radiographic confirmation of inoperable complete resection;
• No previous anti-tumor treatment for metastatic diseases;
• At least one measurable lesion according to RECIST version 1.1;
• Ability to take medications orally;
• No active bleeding;
• Adequate organ functions:

Absolute neutrophil count ≥2×109/L; Platelet ≥100×109/L; Hemoglobin ≥90g/L; WBC≥4×109/L Total bilirubin ≤ 1.5XULN; ALT and AST ≤2.5XULN ； Serum creatinine (Cr) ≤1.5XULN；

• Have fully understood the study and voluntarily signed the informed consent;

Exclusion Criteria:

• Patients who had received any drug in the study protocol in the last year;
• Deficient mismatch repair (dMMR) or MSI-H detected by genetic test;
• HER2 positive（HER-2 3+, or HER-2 2+ and FISH+）;
• Hypertension that could not be controlled by drugs before enrollment was defined as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90 mmHg;
• Patients with acute coronary syndromes (including myocardial infarction and unstable angina) received coronary angioplasty or stenting within 6 months before enrollment;
• Patients with massive pleural or peritoneal effusion requiring drainage;
• Patients with severe ECG abnormalities or heart diseases (such as cardiac insufficiency, myocardial infarction, angina pectoris) that affect clinical treatment;
• Severe lung diseases (such as interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
• Mental disorders or central nervous system diseases or brain metastases affecting clinical treatment;
• Patients with autoimmune diseases;
• Patients with grade 3 or higher bleeding within 4 weeks;
• Patients with a history of allergy to any drug, similar drug or vehicle in this study;
• Had a major surgical procedure (thoracotomy, or laparotomy , etc.) within 4 weeks prior to the first dose of study therapy;
• Patients with nonhealed wounds, ulcers, or fractures;
• Patients who required systemic corticosteroids (excluding temporary testing, prophylactic administration for anaphylaxis), or immunosuppressive agents or had received such agents within 14 days before enrollment;
• Pregnant or lactating women, or patients of childbearing age who refused contraception during the study period;
• Investigators believe that the patient has any other conditions that are not suitable for participating in the study.

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: fruquintinib + tislelizumab + FOLFOX

Drug: fruquintinib + tislelizumab + FOLFOX; phase Ib: fruquintinib (3+3 dose escalation design): L1: 3 mg/d, L2: 4 mg/d, L3: 5 mg/d, qd po, D1-14, Q3W; tislelizumab: 200mg, I.V., D1, Q2W; 5-Fluorouracil: 400mg/m2, D1, followed by 2400 mg/m2 as a continuous IV infusion over 46 hours,Q2W; leucovorin : 400mg/m2, I.V., D1, Q2W; Oxaliplatin: 85mg/m2, ivgtt 2h, D1, Q2W. phase II: fruquintinib: RP2D; tislelizumab: 200mg, I.V., D1, Q2W; 5-Fluorouracil: 400mg/m2, D1, followed by 2400 mg/m2 as a continuous IV infusion over 46 hours,Q2W; leucovorin: 400mg/m2, I.V., D1, Q2W; Oxaliplatin: 85mg/m2, ivgtt 2h, D1, Q2W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Maximum tolerated dose (MTD)	Maximum Tolerated Dose (MTD) of fruquintinib. Investigators leading the study will find the maximum tolerated dose by assessing the rate of serious side effects (known as "dose limiting toxicities") among participants according to the CTCAE 5.0.	At the end of Cycle 1 (each cycle is 21 days)
Phase Ib: RD	To determine the recommended phase 2 dose of fruquintinib, according to the dose limiting toxicities (DLTs).	At the end of Cycle 1 (each cycle is 21 days)
Six-month progression-free survival	The proportion of patients who remain alive and free from disease progression for at least 6 months after initiating treatment.	At six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.	Up to 3 years
OS	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to 3 years
ORR	ORR is defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) per RESISTv1.1.	Up to 3 years
DCR	DCR is defined as the percentage of patients with a best overall response of confirmed complete or partial response, or stable disease (CR+ PR + SD) per RESISTv1.1.	Up to 3 years

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Stomach Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: 2025ZSLYEC-081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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