NCT07175636

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

Not yet recruiting Phase 2 Last updated 16 September 2025

What this trial tests

Phase 2 trial testing Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT) in Locally Advanced Rectal Cancer (LARC) in 66 participants. Not yet recruiting.

Timeline

20 September 2025

Primary endpoint
20 September 2026

20 September 2029

Quick facts

Lead sponsor	Sun Yat-sen University
Phase	Phase 2
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	66
Start date	20 September 2025
Primary completion	20 September 2026
Estimated completion	20 September 2029

Drugs / interventions tested

• Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT) — full drug profile →

Conditions studied

• Locally Advanced Rectal Cancer (LARC) — all drugs for Locally Advanced Rectal Cancer (LARC) →
• Mismatch Repair-Proficient (pMMR) Rectal Cancer — all drugs for Mismatch Repair-Proficient (pMMR) Rectal Cancer →
• Non-metastatic Rectal Cancer — all drugs for Non-metastatic Rectal Cancer →

Sponsor

Sun Yat-sen University

Who can join

Adults 18 to 75, any sex, with Locally Advanced Rectal Cancer (LARC) or Mismatch Repair-Proficient (pMMR) Rectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.