XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma

NCT05494060 | Recruiting Phase 2

• 1 other identifier: 2022-SR-342
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, randomized, phase Ⅱ, multi-cohort study to treat subjects with ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma. The patients will be randomized into two arms consist of Penpulimab + Anlotinib (3 weeks/cycle) + XELOX and XELOX at a ratio of 1:1. This study is conducted to assess safety and anti-tumor activity of the monoclonal antibody Penpulimab in combination with Anlotinib and standard chemotherapy as adjuvant treatment for ctDNA-positive Gastric, or Gastroesophageal Junction Carcinoma.

Conditions

Carcinoma; Gastrointestinal Diseases; Stomach Cancer; Gastroesophageal-junction Cancer; Digestive System Diseases; Gastric Cancer; Gastrointestinal Neoplasms

Keywords

Penpulimab; Anlotinib; Capecitabine; Oxaliplatin; ctDNA; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival (DFS)

  From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence).

  up to 2 years

Secondary Outcomes (2)

• Disease Free Survival (DFS) rate at 2 years

  2 years

• Disease Free Survival (DFS) rate at 3 years

  3 years

Other Outcomes (2)

• Overall survival (OS)

  up to 4 years

• Toxicity by CTCAE v5.0 criteria

  up to 4 years

Study Arms (2)

Penpulimab + Anlotinib + XELOX

EXPERIMENTAL

Penpulimab in combination with Anlotinib and XELOX (Capecitabine and Oxaliplatin)

Drug: Anlotinib hydrochloride capsule; Drug: Penpulimab Injection; Drug: XELOX

XELOX

ACTIVE COMPARATOR

XELOX (Capecitabine and Oxaliplatin)

Drug: XELOX

Interventions

Anlotinib hydrochloride capsule DRUG

Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)；

Penpulimab + Anlotinib + XELOX

Penpulimab Injection DRUG

Penpulimab Injection 100mg per bottle, 200mg IV Day 1, cycled every 21 days

Also known as: AK-105

Penpulimab + Anlotinib + XELOX

XELOX DRUG

Capecitabine:1000 mg/m2 bid d1-14 q3w, Oxaliplatin:130 mg/m2 d1 q3w

Also known as: Capecitabine and Oxaliplatin

Penpulimab + Anlotinib + XELOX; XELOX

Eligibility Criteria

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

You may qualify if:

• Subjects aged ≥18 and ≤75 years old, male or female.
• ECOG performance status score 0-1.
• Histologically or cytologically confirmed GC or GEJ carcinoma, had been treated with Radical resection (D2, R0 or R1) of gastric cancer.
• Pathological stage:III (8th AJCC TNM).
• Estimated lifetime is greater than 6 months.
• The main organs are functioning well, and the blood test results within 14 days before enrollment should meet the following requirements:
• Routine blood test:
• Hemoglobin (HB) ≥90 g/L.
• Neutrophil count (ANC) ≥1.5×109/L.
• Platelet count (PLT) ≥100×109/L.
• Biochemical test:
• Total bilirubin≤1.5×ULN (upper limit of normal).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN.
• Serum creatinine (Cr) ≤1.5 ULN or creatinine clearance ≥60mL/min.
• No obvious clinical symptoms of heart disease.

You may not qualify if:

• Participation in other drug clinical trials within four weeks.
• Multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction.
• History of bleeding, any bleeding event with a severity grade of 3 or higher per CTCAE 5.0 within 4 weeks before screening.
• Patients with known central nervous system metastasis or history of central nervous system metastasis prior to screening. For patients with clinically suspected central nervous system metastases, CT or MRI must be performed within 28 days before enrollment to rule out central nervous system metastases.
• Patients with hypertension and uncontrolled by antihypertensive drugs alone (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg); Patients with a history of unstable angina pectoris; Patients newly diagnosed as angina pectoris within 3 months before screening or myocardial infarction events within 6 months before screening; Arrhythmias (including QTcF ≥ 450 ms in men, ≥ 470 ms in women requiring long-term use of antiarrhythmic drugs and New York Heart Association Class ≥ II cardiac insufficiency;There are many factors that affect oral drug absorption (such as inability to swallow, nausea and vomiting, upper gastrointestinal obstruction, abnormal physiological function, malabsorption syndrome, etc.), which may affect anlotinib hydrochloride absorbers.
• Long-term unhealed wound or unhealed fracture.
• Imaging findings show that the tumor has invaded around important blood vessels or the patient's tumor has a very high possibility of invading important blood vessels during treatment and causing fatal massive hemorrhage as judged by the investigator.
• Patients with abnormal coagulation function and bleeding tendency (the following criteria must be met within 14 days before randomization: INR is within normal range without anticoagulants or has no clinically significant abnormality); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; patients with prothrombin time international normalized ratio (INR) ≤ 1.5 are allowed to take low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (the daily dose does not exceed 100 mg) for preventive purposes.
• Arteriovenous thrombotic events occurred within 6 months before screening, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by previous chemotherapy that has been judged by the investigator to have recovered) and pulmonary embolism.
• Urine routine showed urine protein and 24 h urine protein was confirmed to be \> 1.0g.
• Previous use of immune targeted therapy drugs.
• History of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
• Patients with infectious pneumonia, pneumonitis, interstitial pneumonia and other conditions requiring corticosteroids.
• History of severe chronic autoimmune diseases, such as systemic lupus erythematosus; history of inflammatory bowel disease such as ulcerative enteritis, Crohn's disease, irritable bowel syndrome and other chronic diarrheal diseases; history of sarcoidosis or tuberculosis; history of active hepatitis B, C and HIV infection; well-controlled non-serious immune diseases, such as dermatitis, arthritis, psoriasis, etc. Hepatitis B virus \< 1000 copies/ml can be detected.
• Patients with hypersensitivity to human or murine monoclonal antibodies.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

Related Publications (1)

• Chen Y, Zhang J, Han G, Tang J, Guo F, Li W, Xie L, Xu H, Zhang X, Tian Y, Pan L, Shu Y, Ma L, Chen X. Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study). Front Immunol. 2023 Oct 31;14:1232858. doi: 10.3389/fimmu.2023.1232858. eCollection 2023.

  PMID: 38022553 DERIVED

MeSH Terms

Conditions

Carcinoma; Gastrointestinal Diseases; Stomach Neoplasms; Digestive System Diseases; Gastrointestinal Neoplasms

Interventions

penpulimab; XELOX; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Ext: Shu, PhD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongqian Shu, PhD

CONTACT

0086-025-68306428; shuyongqian@csco.org.cn

Xiaofeng Chen, PhD

CONTACT

0086-13585172006; xiaofengch198019@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experimental: Penpulimab + Anlotinib + XELOX； Active Comparator: XELOX

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 9, 2022
• Study Start: March 16, 2022
• Primary Completion: December 1, 2024
• Study Completion (Estimated): February 1, 2027
• Last Updated: November 7, 2023

Record last verified: 2023-11

Locations

CN (1)