Short-course Radiotherapy Combined With Retlirafusp Alfa and CAPOX Chemotherapy as Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Prospective, Single-arm, Phase II Clinical Study

NCT07663071 | Active Not Recruiting Phase 2

• 1 other identifier: SHR-1701-HLJ-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy combined with Retlirafusp alfa and CAPOX chemotherapy in the treatment of locally advanced rectal cancer. This is a prospective, single-arm, phase II clinical trial planned to enroll 44 patients with locally advanced rectal cancer. The primary endpoint is the complete response rate, and secondary endpoints include objective response rate, pathological complete response rate, event-free survival, and overall survival, with the goal of providing evidence to optimize clinical treatment decisions.

Conditions

Rectal Cancer Patients

Keywords

locally advanced rectal cancer; Retlirafusp alfa; neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (cCR+pCR)

  Proportion of patients achieving clinical complete response (cCR, no tumor residue by imaging and endoscopy) after neoadjuvant therapy or pathological complete response (pCR, no residual viable tumor cells in tumor bed) post-surgery, reflecting overall tumor eradication.

  cCR assessed 2-4 weeks post-neoadjuvant therapy; pCR assessed within 2 weeks post-surgery; follow-up up to ~6 months.

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Imaging assessment after cycles 2 and 4, and post-surgery; follow-up up to ~6 months.

• Pathological Complete Response (pCR)

  Pathological assessment within 2 weeks post-surgery; follow-up up to ~6 months.

• Major Pathological Response (MPR)

  Pathological assessment within 2 weeks post-surgery; follow-up up to ~6 months.

• TRG Grade

  Pathological assessment within 2 weeks post-surgery; follow-up up to ~6 months.

• Event-Free Survival (EFS)

  From treatment initiation to first event, follow-up every 3 months, up to 36 months.

Study Arms (1)

Short-course radiotherapy combined with Retlirafusp alfa and CAPOX chemotherapy

EXPERIMENTAL

Short-course radiotherapy combined with Retlirafusp alfa and CAPOX chemotherapy

Drug: Short-course radiotherapy combined with Retlirafusp alfa and CAPOX chemotherapy

Interventions

Short-course radiotherapy combined with Retlirafusp alfa and CAPOX chemotherapy DRUG

Short-course radiotherapy + Retlirafusp alfa + CAPOX chemotherapy for 1 cycle, followed by Retlirafusp alfa + CAPOX chemotherapy for 3 cycles. Cycle 1: Retlirafusp alfa: 1800 mg or 30 mg/kg, IV infusion over 30-60 min, D1, q3w; administered at least 30 min before chemotherapy. Oxaliplatin: 130 mg/m², IV infusion over ≥2 h, D1, q3w. Capecitabine: 1000 mg/m², PO, twice daily (total 2000 mg/m²/day) for 14 days, q3w. Short-course radiotherapy: 25 Gy in 5 fractions, D2-D6. Cycles 2-4: Retlirafusp alfa: 1800 mg or 30 mg/kg, IV infusion over 30-60 min, D1, q3w. Oxaliplatin: 130 mg/m², IV infusion over ≥2 h, D1, q3w. Capecitabine: 1000 mg/m², PO, twice daily (total 2000 mg/m²/day) for 14 days, q3w. Efficacy evaluation is performed after cycles 2 and 4. Patients are reassessed 2-4 weeks after the last treatment. Those achieving clinical complete response (cCR) may opt for watch-and-wait (W\&W). Non-cCR patients (near-CR, PR, or SD) are recommended to undergo total mesorectal excision (

Short-course radiotherapy combined with Retlirafusp alfa and CAPOX chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years, male or female.
• Histologically or cytologically confirmed rectal adenocarcinoma, stage T3N+M0 or T4NanyM0 (AJCC/UICC TNM 8th edition), with measurable lesion(s) per RECIST 1.1.
• Tumor lower border 5-10 cm from the anal verge.
• Expected to achieve R0 resection after neoadjuvant therapy, and planned for surgery thereafter.
• ECOG PS 0-1.
• No prior anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, immune checkpoint inhibitors, or surgery.
• Adequate organ function (without blood product or growth factor support during screening):
• ANC ≥1.5×10⁹/L; platelets ≥100×10⁹/L; hemoglobin ≥8.5 g/dL.
• TSH ≤1×ULN (if abnormal, T3/T4 must be within normal limits for enrollment).
• Bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN.
• Serum creatinine ≤1.5×ULN or CrCl ≥50 mL/min (Cockcroft-Gault formula).
• INR ≤1.5×ULN; APTT ≤1.5×ULN.
• Negative pregnancy test (β-hCG) for women of childbearing potential before treatment initiation.Women of childbearing potential and men (who are sexually active with women of childbearing potential) must agree to use effective contraception continuously during treatment and for 6 months after the last dose.
• Voluntary participation with written informed consent.

You may not qualify if:

• History of other malignancies within the past 5 years, except adequately treated cervical carcinoma in situ, cutaneous squamous cell carcinoma, or basal cell carcinoma.
• Major surgery or severe trauma within 4 weeks prior to first study drug administration.
• Systemic corticosteroids (equivalent to prednisone \>10 mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
• Active, known, or suspected autoimmune disease. Patients with stable conditions not requiring systemic immunosuppression (e.g., type 1 diabetes, hypothyroidism on hormone replacement, or skin disorders without systemic treatment) are eligible.
• Immunodeficiency, including HIV positivity, other acquired/congenital immune deficiencies, or history of organ or allogeneic bone marrow transplantation.
• Congestive heart failure, uncontrolled arrhythmia, myocardial infarction within 6 months, unstable angina, stroke, or other conditions precluding surgery.
• Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired pulmonary function.
• Uncontrolled symptomatic brain metastases, poorly controlled psychiatric disorders, or severe intellectual/cognitive impairment.
• Known substance abuse or drug addiction.
• Clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment.
• Severe active infection requiring IV antibiotics during screening.
• Known hypersensitivity to Retlirafusp alfa or any excipients (polysorbate 80 (II), sucrose, citric acid, sodium citrate, water for injection, etc.), or severe allergic reactions to other monoclonal antibodies.
• Active hepatitis B (HBV DNA \>2000 IU/mL or 10⁴ copies/mL), or hepatitis C antibody-positive with HCV RNA above the lower limit of detection.
• Receipt or planned receipt of live vaccine within 30 days prior to immunotherapy administration.
• Intolerance to chemotherapy.

Sponsors & Collaborators

• Harbin Medical University: lead

Study Sites (1)

Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, China

Harbin, Heilongjiang, 150081, China

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: June 23, 2026
• Study Start: May 27, 2026
• Primary Completion (Estimated): May 27, 2028
• Study Completion (Estimated): May 27, 2029
• Last Updated: June 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)