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

NCT06884670 | Completed Phase 2 DMC

• 1 other identifier: PICM
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 4

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.

Conditions

Rectal Cancer

Keywords

Tislelizumab; Interleukin-2; MSS/pMMR rectal cancer

Outcome Measures

Primary Outcomes (3)

• Pathological Complete Response rate (pCR)

  1 year

• Clinical complete response (cCR)

  1 years

• near cCR

  1 years

Secondary Outcomes (5)

• Safety and Tolerability

  1 month

• Overall survival

  3 years

• Disease free survival (DFS)

  3 years

• MPR

  1 year

• R0 resection rate

  1 year

Study Arms (2)

Conventional Neoadjuvant Group

ACTIVE COMPARATOR

Patients in the CRT group received long-course radiotherapy to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, delivered 5 days per week with three-dimensional conformal radiotherapy, VMAT, or IMRT. Concurrent capecitabine was given orally at 825 mg/m² twice daily on days 1-5 each week for 5 weeks. After radiotherapy, patients received four cycles of CapeOX: oxaliplatin 130 mg/m² intravenously on day 1 and capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle

Radiation: Radiotherapy; Drug: Oxaliplatin; Drug: Capecitabine

PD-1+IL-2+CapeOX group

EXPERIMENTAL

Patients in the PICM group received 21-day cycles of tislelizumab 200 mg intravenously on day 1, oxaliplatin 130 mg/m² intravenously on day 1, capecitabine 1000 mg/m² orally twice daily on days 1-14, and recombinant human IL-2 1 million IU subcutaneously on Monday, Wednesday, and Friday during days 1-14, for six doses per cycle. Rectal MRI was done after two cycles. Patients with tumor regression greater than 20% continued to six cycles; those with regression less than 20%, local progression, or distant metastasis discontinued protocol treatment and received subsequent treatment at the investigator's discretion.

Drug: Interleukin-2; Drug: Tislelizumab; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Interleukin-2 DRUG

Tislelizumab 200mg ivd D1+Interleukin 2 100IU HD, d1-d14+ CapeOX (Capecitabine: 825mg/m2 bid po, d1-d14；Oxaliplatin 200 mg/m² ivd, d1)

PD-1+IL-2+CapeOX group

Radiotherapy RADIATION

Radiotherapy 1.8Gy per time\*28

Conventional Neoadjuvant Group

Tislelizumab DRUG

Tislelizumab 200mg ivd D1

PD-1+IL-2+CapeOX group

Oxaliplatin DRUG

Oxaliplatin 200 mg/m² ivd, d1

Conventional Neoadjuvant Group; PD-1+IL-2+CapeOX group

Capecitabine DRUG

Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle

Conventional Neoadjuvant Group; PD-1+IL-2+CapeOX group

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.
• Patients who have previously received systemic anticancer therapy for colorectal cancer; or have been treated with PD-1, PD-L1, or CTLA-4 antibodies.
• 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.
• Patients with interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (such as diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
• 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.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (4)

Nanjing BenQ Hospital

Nanjing, Jiangsu, 210000, China

Location

Jiangsu province hospital

Nanjing, Jiangsu, 210029, China

Location

Xuzhou Central hospital

Xuzhou, Jiangsu, China

Location

The Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Interleukin-2; Radiotherapy; tislelizumab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Therapeutics; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

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

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: March 19, 2025
• Study Start: August 18, 2024
• Primary Completion: May 31, 2026
• Study Completion: June 1, 2026
• Last Updated: June 24, 2026

Record last verified: 2025-03

Locations

CN (4)