Assessment of Efficacy and Safety of PD-1 Monoclonal Antibody Combined With IL-2 and CapeOX in Neoadjuvant Therapy for Locally Advanced Rectal Cancer Prior to Surgery: A Prospective, Multi-center, Randomized Controlled Study

Phase 2

Not yet recruiting

• Conditions: Rectal Cancer
• Interventions: Radiation: Radiotherapy; Drug: Interleukin-2; Drug: Oxaliplatin; Drug: Tislelizumab; Drug: Capecitabine

• Registration Number: NCT06884670
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

The objective is to evaluate whether the neoadjuvant combination of tislelizumab (a PD-1 inhibitor) with interleukin-2 (IL-2) chemotherapy can significantly increase the Objective Response Rate (ORR) and the Pathological Complete Response rate (pCR) in patients with locally advanced rectal cancer who have Microsatellite Stable/Proficient Mismatch Repair (MSS/pMMR) status.

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 recent years, substantial advancements have reshaped the landscape of CRC treatment, offering new hope and improved outcomes for affected individuals. Surgical intervention remains the cornerstone of curative therapy, guided by tumor stage, location, and patient's overall health status. Adjuvant therapies, including chemotherapy and radiotherapy, have been pivotal in reducing recurrence rates and enhancing overall survival. Targeted treatments, such as anti-EGFR and anti-VEGF drugs, have ushered in an era of precision medicine, selectively targeting critical molecular pathways. Meanwhile, immunotherapy, particularly immune checkpoint inhibitors, has emerged as a promising frontier, offering personalized treatment options for CRC patients.

In CRC, the PD-1 inhibition pathway plays a central role in regulating immune cell exhaustion; however, the response to PD-1 monotherapy is limited in a majority of colorectal cancer patients, suggesting that combining PD-1 blockade with other immunostimulatory agents holds promise. Currently, several combination therapies have shown progress in animal models and are being explored in clinical studies. Among these, interleukin-2 (IL-2) emerges as a candidate drug, synergizing with PD-1 blockade to potentiate antitumor effects. This study aims to investigate the combination of IL-2 with PD-1 inhibitors, seeking to overcome the limitations of single-agent immunotherapy through multifaceted immunomodulation. By modulating the immune microenvironment to enhance immune cell infiltration and break down the physical and immunosuppressive barriers of the tumor, this approach seeks to augment the efficacy of immunotherapy, particularly for immunologically cold CRC patients.

Study Timeline

• Study First Submitted: 2024-07-11
• Status Verified: 2025-03
• Study Start: 2025-03-18
• Study First Submitted QC: 2025-03-18
• Last Update Submitted: 2025-03-18
• Study First Posted: 2025-03-19
• Last Update Posted: 2025-03-19
• Primary Completion: 2025-07-10
• Study Completion: 2027-07-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Males and females aged between 18 and 75 years;
2. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
3. Histologically confirmed rectal adenocarcinoma;
4. Clinical stage T3-T4 or any T with node-positive (N+) disease: locally advanced;
5. Microsatellite stable (MSS) status;
6. Adequate hematological, hepatic, and renal functions.

Exclusion Criteria

1. Patients with metastatic disease (Stage IV); recurrent colorectal cancer with active bleeding, perforation, or complex conditions requiring urgent surgery; or concurrent non-colorectal cancer malignancies.
2. Patients who have previously received systemic anticancer therapy for colorectal cancer; or have been treated with PD-1, PD-L1, or CTLA-4 antibodies.
3. Patients with any active autoimmune disease; known or tested positive for Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS); or a history requiring steroid or immunosuppressive drug treatment.
4. Patients with interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (such as diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
5. Patients who experienced any Grade 2 or higher toxicities due to prior treatments (as classified by the Common Terminology Criteria for Adverse Events [CTCAE] version 5), which have not resolved (excluding anemia, alopecia, and skin pigmentation changes); known or suspected history of hypersensitivity to any of the drugs used in the trial.
6. Pregnant or breastfeeding women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional Neoadjuvant Group	Radiotherapy	Radiotherapy 1.8Gy per time\*28 And Capecitabine: 825mg/m2 bid po, a total of 28 days CapeOX 2 cycles (Capecitabine: 825mg/m2 bid po, d1-d14；Oxaliplatin 200 mg/m² ivd, d1
Conventional Neoadjuvant Group	Oxaliplatin	Radiotherapy 1.8Gy per time\*28 And Capecitabine: 825mg/m2 bid po, a total of 28 days CapeOX 2 cycles (Capecitabine: 825mg/m2 bid po, d1-d14；Oxaliplatin 200 mg/m² ivd, d1
Conventional Neoadjuvant Group	Capecitabine	Radiotherapy 1.8Gy per time\*28 And Capecitabine: 825mg/m2 bid po, a total of 28 days CapeOX 2 cycles (Capecitabine: 825mg/m2 bid po, d1-d14；Oxaliplatin 200 mg/m² ivd, d1
PD-1+IL-2+CapeOX group	Interleukin-2	Tislelizumab 200mg ivd D1+Interleukin 2 100IU HD, d1-d14+ CapeOX (total 6 cycles)
PD-1+IL-2+CapeOX group	Tislelizumab	Tislelizumab 200mg ivd D1+Interleukin 2 100IU HD, d1-d14+ CapeOX (total 6 cycles)
PD-1+IL-2+CapeOX group	Oxaliplatin	Tislelizumab 200mg ivd D1+Interleukin 2 100IU HD, d1-d14+ CapeOX (total 6 cycles)
PD-1+IL-2+CapeOX group	Capecitabine	Tislelizumab 200mg ivd D1+Interleukin 2 100IU HD, d1-d14+ CapeOX (total 6 cycles)

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	1 years
Pathological Complete Response rate (pCR)	1 year

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability	1 month