NCT06504875

Application of PD-1 Monoclonal Antibody in Combination With IL-2 and CapeOX in Organ Preservation Therapy for Ultra-Low Localized Advanced Rectal Cancer

Application of PD-1 Monoclonal Antibody in Combination With IL-2 and CapeOX in Organ Preservation Therapy for Ultra-Low Localized Advanced Rectal Cancer: A Single-center, Single-arm, Open-label Clinical Study (PICTURE)

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 23 (estimated)
• Sponsor: The First Affiliated Hospital with Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The objective is to evaluate whether the neoadjuvant combination of PD-1 inhibitor tislelizumab and interleukin-2 (IL-2) can significantly enhance the complete response rate (cCR + local excision pCR) and organ preservation rate in patients with MSS/pMMR locally advanced rectal cancer.

Detailed description

Colorectal cancer (CRC) stands as a prominent global health concern, ranking among the most prevalent malignancies worldwide. Its incidence exhibits striking geographical variations, with higher rates observed in developed countries. Age is a significant risk factor, predominantly affecting individuals aged 50 and above, although a concerning trend of increasing incidence in younger adults has been noted in recent years. There exists a gender disparity, with slightly higher prevalence in males. Notably, lifestyle factors, including dietary choices, sedentary habits, smoking, and obesity, play crucial roles in its etiology. These epidemiological patterns underscore the urgency for implementing effective prevention strategies and advancing early detection methods to mitigate the disease's impact. In China, nearly two-thirds of colorectal cancer cases are rectal cancers, with approximately half being low rectal cancers. Currently, surgical resection remains the primary curative approach for patients with low rectal cancer. The concept of Total Mesorectal Excision (TME), introduced in 1982, has become the standard surgical procedure for low rectal cancer, focusing on en bloc removal of the rectum along with its mesentery to reduce the local recurrence rate post-surgery. Building upon this, the advent of neoadjuvant chemoradiotherapy, watch-and-wait strategies, targeted therapies, and immunotherapies has shifted the focus of low rectal cancer management from merely increasing R0 resection rates and decreasing local tumor recurrence to encompassing precise imaging-based staging, efficacy assessment, organ function preservation, and quality-of-life improvements. In colorectal cancer, the PD-1 inhibition pathway plays a central role in regulating immune cell exhaustion. However, monotherapy targeting PD-1 alone shows limited responses in most colorectal cancer patients, suggesting that combinations with other immunostimulatory agents could address this challenge. Several combinatorial approaches have shown promise in animal models and are now being explored in clinical settings. Among these, Interleukin-2 (IL-2) is emerging as a potential candidate to synergize with PD-1 blockade in exerting antitumor effects. Our study aims to explore the synergy of IL-2 combined with a PD-1 inhibitor, seeking to overcome the limitations of single-agent immunotherapy through multifaceted immune modulation. By enhancing immune cell infiltration and disrupting the physical and immunosuppressive barriers of tumors, we aim to augment the efficacy of immunotherapy and increase the organ preservation rate in ultra-low locally advanced rectal cancer.

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
DRUG	Tislelizumab	Tislelizumab 200mg ivd D1
DRUG	Interleukin-2	Interleukin 2 100IU HD,QOD d1-d14
DRUG	Capecitabine	Capecitabine: 1000mg/m2 bid po, d1-d14
DRUG	Oxaliplatin	Oxaliplatin 130mg/m2 ivd, d1

Timeline

• Start date: 2024-07-10
• Primary completion: 2025-07-10
• Completion: 2027-07-10
• First posted: 2024-07-17
• Last updated: 2024-07-17