Fruquintinib Plus PD-1 Antibody in pMMR / MSS Locally Advanced Rectal Cancer (LARC) With High Immune Score

NCT04989855 | Unknown Phase 2

• 1 other identifier: HMPL-013-FLAG-C105
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, one arm phase II study aimed to observe the efficacy and safety of tislelizumab combined with fruquintinib in treatment of patients with pMMR / MSS locally advanced rectal cancer with high immune score.

Conditions

Locally Advanced Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate

  up to 3 years

Secondary Outcomes (3)

• 3-year RFS

  up to 3 years

• 3-year OS

  up to 3 years

• Safety and Tolerability

  up to 3 years

Study Arms (1)

Fruquintinib plus Tislelizumab

EXPERIMENTAL

Fruquintinib 5mg QD d1-d14, Q3W; Tislelizumab 200mg IV Q3W d1

Drug: Fruquintinib plus Tislelizumab

Interventions

Fruquintinib plus Tislelizumab DRUG

2 cycles of Fruquintinib(F) 5mg QD d1-d14 + Tislelizumab(T) 200mg IV d1, Q3W as preoperative therapy, and F +T after TME as postoperative therapy for 6 months

Fruquintinib plus Tislelizumab

Eligibility Criteria

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

You may qualify if:

• yrs old;
• pMMR/MSS rectal adenocarcinoma;
• Pelvic MRI / endoscopic ultrasonography or transrectal ultrasound were used for reoperative staging: T3-4N+ with resectable tumor;
• High immune score (Immunoscore®️ ≥3);
• No sign of bowel obstruction, or bowel obstruction has been relieved by ostomy;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• No previous chemotherapy, radiotherapy or immunotherapy;
• Distant metastasis was excluded by CT of chest, abdomen and pelvis before operation;
• Able to swallow tablets;
• Life expectancy of at least 2 years;
• Adequate organ function;
• Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose; Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose.

You may not qualify if:

• Any active autoimmune disease or history of autoimmune disease;
• Immunosuppressants, systemic or absorbable local hormones are being used to achieve the purpose of immunosuppression (dose \> 10mg / day, prednisone or other effective hormones) and continue to be used within 2 weeks before enrollment;
• History of severe allergic reaction to monoclonal antibody;
• Subjects with untreated active brain metastasis or meningeal metastasis with clinical symptoms;
• Suffering from hypertension and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg);
• Have previously received other PD-1 antibody therapy or other immunotherapy against PD-1 / PD-L1, or have previously received anti angiogenesis drugs;
• There are cardiac clinical symptoms or diseases that are not well controlled, such as: (1) heart failure above NYHA grade 2 (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• Known hereditary or acquired bleeding and thrombotic tendency (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.) or undergoing thrombolytic or anticoagulant therapy;
• Urine routine examination indicates that urinary protein is ≥ + +, or confirmed 24-hour urinary protein is ≥ 1.0g;
• Significant clinical bleeding symptoms or definite bleeding tendency occurred within 3 months before enrollment, such as gastrointestinal bleeding, active bleeding, baseline fecal occult blood + + or above, or vasculitis;
• Arteriovenous thrombosis events occurred within 6 months before enrollment, such as cerebrovascular accidents (including transient ischemic attack, intracerebral hemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism;
• Subjects with active infection;
• Congenital or acquired immune deficiency (such as HIV infection) or active hepatitis (hepatitis B: HBsAg positive and HBV DNA \> 104 copy number /ml; Hepatitis C: HCV antibody positive);
• Those who participated in clinical trials of other drugs within 3 months before enrollment;
• There was evidence of distant metastasis before operation;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

651 Dongfeng Road East

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

HMPL-013; tislelizumab

Central Study Contacts

Pei-Rong Ding, M.D.

CONTACT

8602087343920; dingpr@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 4, 2021
• Study Start: August 1, 2021
• Primary Completion: August 1, 2022
• Study Completion: February 1, 2024
• Last Updated: August 4, 2021

Record last verified: 2021-08

Locations

CN (1)