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

NCT06871527 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2025ZSLYEC-081
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric (Stomach) Cancer; Gastric Adenocarcinoma; Fruquintinib; PD-1 Inhibitor; Tislelizumab; GEJ Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• PFS

  Up to 3 years

• OS

  Up to 3 years

• ORR

  Up to 3 years

• DCR

  Up to 3 years

Study Arms (1)

fruquintinib + tislelizumab + FOLFOX

EXPERIMENTAL

fruquintinib + tislelizumab + FOLFOX

Drug: fruquintinib + tislelizumab + FOLFOX

Interventions

fruquintinib + tislelizumab + FOLFOX DRUG

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.

fruquintinib + tislelizumab + FOLFOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

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

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 210000, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

HMPL-013; tislelizumab; Folfox protocol

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xiaohui Zhai

CONTACT

862038285497; zhaixh@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: March 12, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 12, 2025

Record last verified: 2025-03

Locations

CN (1)