NCT06491355

First-Line Treatment Induced With mFOLFOX6 and HLX04 Regimen, Following Combined With Serplulimab in MSS Initially Unresectable Metastatic Colorectal Cancer

Efficacy and Safety of First-Line Treatment Induced With mFOLFOX6 and HLX04 Regimen, Following Combined With Serplulimab in MSS Initially Unresectable Metastatic Colorectal Cancer: A Prospective, Multicenter, Randomized, Controlled Trial (ASTRUM-IUmCRC)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: Sir Run Run Shaw Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, multi-center, randomized controlled clinical intervention study, aiming to explore the effectiveness and safety of mfolfox6 and hlx04 regimens combined with slulimumab as first-line treatment for MSS-type initial unresectable metastatic colorectal cancer after induction therapy. This study plans to include a total of 72 patients with untreated MSS-type initial unresectable metastatic colorectal cancer. This study randomly allocated groups through a randomization system, and entered the following treatment groups at a ratio of 1:1: (1) Experimental group: mfolfox6 and hlx04 regimen induction therapy followed by slulimab treatment (36 cases); (2) Control group Group: mfolfox6 and hlx04 regimen treatment (36 cases).

Detailed description

Colorectal Cancer (CRC) is a common malignant tumor. Its incidence ranks third and second among men and women respectively, and its mortality rate ranks third. Data from the World Health Organization's International Agency for Research on Cancer (IARC) in 2020 show that more than 930,000 patients died due to CRC. Since 2000, the incidence and mortality of colorectal cancer have been steadily increasing in China. The National Cancer Center of China (NCC) reported that there were approximately 408,000 new cases of CRC in China in 2016, and approximately 196,000 deaths. Most of the patients are in the mid-to-late stage when diagnosed, and about 35% of them are in the advanced stage. They have no chance of radical surgery and can only receive palliative care. In the early days when leucovorin (LV) and 5-fluorouracil (5-FU) were used as the main treatment options for patients with metastatic colorectal cancer (mCRC), the efficacy was poor, and the median overall survival (OS) of patients was only for 8-12 months. Since the introduction of effective cytotoxic drugs such as irinotecan and oxaliplatin in 2000, the combination regimens FOLFOX (5-FU/LV + oxaliplatin) and FOLFIRI (5-FU/LV + irinotecan) have become first-line systemic Standard protocol in treatment. The use of biologics targeting key pathways in the development and progression of mCRC, such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)-related pathways, further extends the survival of mCRC patients. In the latest version of CSCO colorectal cancer diagnosis and treatment guidelines, the main recommended first-line treatments are FOLFOX/FOLFIRI±bevacizumab or cetuximab (both RAS and BRAF are wild-type), FOLFOX/FOLFIRI±bevacizumab (RAS or BRAF mutant). PD-1 plays an important role in suppressing immune responses and promoting immune tolerance by inhibiting the activity of T cells, allowing cancer cells to evade immune surveillance. Cells in the tumor microenvironment often express PD-1 and PD-L1. Consistent with the inducible expression of PD-L1 by tumor cells, activated CD8+ effector T cells often express PD-1, indicating that tumor cells are resistant to adaptive immune responses. PD-L1 has been found to be expressed in many types of cancer, including melanoma, lung cancer, urothelial cancer, and hepatocellular carcinoma. Its expression can also be induced by various factors such as radiation, which helps cancer cells evade immune regulation. Blocking the PD-1/PD-L1 interaction has been shown to treat a variety of cancers. Clinical studies have proven that anti-PD-1 and anti-PD-L1 monoclonal antibodies can induce long-lasting anti-tumor activity against a variety of tumors. Anti-PD-1 monoclonal antibodies have been approved for the treatment of melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, entities with high microsatellite instability or mismatch repair deficiency and colorectal cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma (HCC), Merkel cell carcinoma (MCC), renal cell carcinoma, endometrial cancer, bladder cancer, primary mediastinal large B-cell lymphoma ( PMBCL) and classic Hodgkin lymphoma. A large number of clinical studies of anti-PD-1 antibodies are currently underway, some as monotherapy and some in combination with multiple drugs. This study is an open-label, single-arm, phase II clinical trial. The study inclusion criteria are patients with unresectable mCRC aged 18-75 years old and histologically confirmed by multidisciplinary treatment (MDT). The patients have RAS gene mutations and are confirmed to be MSS. state. All patients received treatment with sintilimab combined with CapeOx and bevacizumab. After the disease achieved complete response (CR)/partial response (PR)/stable disease (SD), maintenance treatment was performed. The main purpose of the study Endpoints include objective response rate (ORR) as assessed by RECIST v1.1 and adverse events as assessed by CTCAE v5.0. The secondary endpoint is progression-free survival (PFS). This study mainly aims to explore the effectiveness of chemotherapy and bevacizumab induction therapy combined with PD-1 monoclonal antibody in the first-line treatment of MSS-type initial unresectable metastatic colorectal cancer. The second is its safety and tolerability.

Conditions

• Efficacy, Self
• Safety Issues
• Colo-rectal Cancer

Interventions

Type	Name	Description
DRUG	mfolfox6 and hlx04 regimen and Serplulimab	mfolfox6 and hlx04 regimen induction therapy followed by combined treatment with slulimumab in the experimental arm. In the active comparator. only with mfolfox6 and hlx04 regimen treatment.
DRUG	mfolfox6 and hlx04 regimen	In the active comparator. only with mfolfox6 and hlx04 regimen treatment.

Timeline

• Start date: 2024-07-01
• Primary completion: 2025-06-30
• Completion: 2026-06-30
• First posted: 2024-07-09
• Last updated: 2024-07-09

Locations

1 site across 1 country: China