Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX...

About this study

This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Early response will be assessed after 2 cycles using endoscopy and pelvic MRI to guide subsequent treatment: participants with partial response may discontinue radiotherapy and continue neoadjuvant systemic therapy; participants with stable disease may switch to standard chemoradiotherapy; participants with progressive disease will receive multidisciplinary-team-guided salvage therapy. After 4 cycles, participants with clinical complete response may adopt a watch-and-wait strategy; otherwise, they will undergo radical surgery 2-4 weeks after completion of neoadjuvant therapy. Long-term follow-up will include recurrence and survival outcomes and quality of life.

Condition: Colorectal Cancer (CRC)
Tested: Low-dose radiotherapy, Pucotenlimab, CAPEOX/XELOX
Sponsor: Sun Yat-sen University

Who can join

Age: 18 to 75 years
Sex: All sexes
Healthy volunteers: Not accepted

Inclusion 22

Minimum age: 18 years
Maximum age: 75 years
Study condition: Colorectal Cancer (CRC)
Written informed consent provided prior to any study-specific procedures.
Age 18 to 75 years at the time of enrollment.
Histologically confirmed rectal adenocarcinoma.
Tumor located within 10 cm from the anal verge, as assessed by endoscopy or imaging.
Locally advanced disease, defined as clinical stage T2N+ or T3-T4a (any N) based on pelvic magnetic resonance imaging (MRI).
Proficient mismatch repair (pMMR) or microsatellite-stable (MSS) tumor status confirmed by immunohistochemistry or molecular testing.
No evidence of distant metastasis on preoperative imaging, including chest, abdominal, and pelvic computed tomography (CT).
Circumferential resection margin (CRM) ≥2 mm and no involvement of the mesorectal fascia on baseline MRI.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Adequate organ function as defined by:
Absolute neutrophil count ≥1.5 × 10⁹/L
Platelet count ≥100 × 10⁹/L
Hemoglobin ≥90 g/L
Total bilirubin ≤1.5 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
Creatinine clearance ≥50 mL/min
Thyroid-stimulating hormone (TSH) within normal limits
Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for a protocol-defined period after the last dose.
Men with partners of childbearing potential must agree to use effective contraception during the study and for a protocol-defined period after the last dose.

Exclusion 14

Clinical T4b disease, defined as tumor invasion into adjacent organs or structures on baseline imaging.
Circumferential resection margin (CRM) \<2 mm or definite involvement of the mesorectal fascia on baseline MRI.
Evidence of distant metastasis outside the pelvis.
Prior pelvic or abdominal radiotherapy.
Prior treatment with immune checkpoint inhibitors or other systemic anticancer therapy for rectal cancer.
Active or history of autoimmune disease requiring systemic treatment, except for conditions considered low risk for recurrence (e.g., vitiligo, resolved childhood asthma).
Ongoing use of systemic immunosuppressive therapy, including corticosteroids equivalent to \>10 mg/day of prednisone, within 2 weeks prior to enrollment.
Known human immunodeficiency virus (HIV) infection.
Active hepatitis B virus infection with positive hepatitis B surface antigen and high viral load, or hepatitis C virus infection requiring treatment.
Uncontrolled active infection or other serious medical condition that, in the investigator's judgment, would compromise patient safety or study compliance.
History of another malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies with negligible risk of recurrence.
Known hypersensitivity or allergy to pucotenlimab, oxaliplatin, capecitabine, or any of their excipients.
Pregnant or breastfeeding women.
Any condition that, in the investigator's opinion, makes the participant unsuitable for study participation.

Where

1 site, 1 recruiting

Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651

Guangzhou, Guanggong, China

Recruiting

Contact