Not Yet RecruitingPhase 2

QL1706 With Short-Course Radiotherapy and Chemotherapy for MSS Rectal Cancer

66 participantsStarted 2025-09-20

Plain-language summary

This is a multicenter, prospective, phase II study evaluating total neoadjuvant therapy (TNT) consisting of short-course radiotherapy (SCRT; 5×5 Gy) followed by QL1706 (a bifunctional MabPair antibody targeting PD-1 and CTLA-4, code name only) plus mFOLFOX6 chemotherapy in patients with locally advanced rectal cancer (LARC) with proficient mismatch repair/microsatellite-stable (pMMR/MSS) biology. Patients with pMMR/MSS disease derive limited benefit from immune checkpoint inhibition alone. Preclinical and clinical evidence suggests that SCRT and oxaliplatin-based chemotherapy can enhance antitumor immunity (e.g., antigen release, T-cell infiltration), providing a biological rationale for combining QL1706 with SCRT-primed TNT. Eligible adults with cT3-4 and/or N+ mid-to-low rectal adenocarcinoma (without distant metastasis), confirmed pMMR/MSS, and ECOG 0-1 will receive: SCRT (total 25 Gy over 5 fractions), then several cycles of QL1706 plus mFOLFOX6 as neoadjuvant systemic therapy. Definitive total mesorectal excision (TME) is planned per multidisciplinary assessment; a watch-and-wait approach may be considered for patients achieving a stringent clinical complete response per institutional criteria. Standard perioperative care and postoperative follow-up will be performed. Primary endpoint is pathologic complete response (pCR, ypT0N0) rate at surgery. Key secondary endpoints include: clinical complete response (cCR) rate, major pathologic response rate, R0 resection rate, tumor downstaging, radiologic response, disease-free survival (DFS), overall survival (OS), organ preservation rate (for patients managed non-operatively), surgical morbidity, and safety/tolerability (CTCAE v5.0). Exploratory endpoints include correlations between efficacy and baseline clinicopathologic features; optional translational analyses may investigate immune-inflammation markers related to response and resistance. This trial aims to determine whether SCRT-primed QL1706 plus mFOLFOX6 TNT can improve tumor eradication and organ preservation while maintaining acceptable safety in pMMR/MSS LARC-a population with unmet need for effective immunotherapy-based strategies.

Who can participate

Age range

18 Years – 75 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: Age 18-75 years, male or female. Histologically confirmed rectal adenocarcinoma. Locally advanced disease (cT3-4 and/or N+, M0) based on pelvic MRI and/or CT. Tumor located within 12 cm from the anal verge. Proven microsatellite stability (MSS) or proficient mismatch repair (pMMR) status. ECOG performance status 0-1. Adequate organ function: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Hemoglobin ≥ 90 g/L ALT/AST ≤ 2.5 × ULN Total bilirubin ≤ 1.5 × ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min No prior pelvic radiotherapy, chemotherapy, immunotherapy, or targeted therapy for rectal cancer. Signed written informed consent Exclusion Criteria: Evidence of distant metastasis. Previous or concurrent malignant tumor (except cured basal cell carcinoma of skin or cervical carcinoma in situ). Active autoimmune disease requiring systemic immunosuppressive therapy. Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis. Known allergy or hypersensitivity to study drugs or excipients. Uncontrolled cardiovascular disease (e.g., recent myocardial infarction, unstable angina, congestive heart failure, arrhythmia). Pregnant or breastfeeding women. Any condition judged by investigators to make the patient unsuitable for the study.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Pathologic Complete Response (pCR) Rate

Timeframe: At the time of surgery following completion of total neoadjuvant therapy (approximately 16-24 weeks after enrollment).

Trial details

NCT IDNCT07175636

SponsorSun Yat-sen University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-09-20

Contact for this trial

Zhenhai Lu, MD

+862087343124 luzhh@sysucc.org.cn

View on ClinicalTrials.gov More Locally Advanced Rectal Cancer (LARC) trials