QL1706 With Short-Course Radiotherapy and Chemotherapy for MSS Rectal Cancer
NCT ID: NCT07175636
Last Updated: 2025-09-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE2
66 participants
INTERVENTIONAL
2025-09-20
2029-09-20
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Short-Course Radiotherapy Followed by QL1706 Plus mFOLFOX6
Participants will receive short-course radiotherapy (SCRT, 25 Gy in 5 fractions over one week) followed by total neoadjuvant therapy (TNT) consisting of QL1706 (a bifunctional MabPair antibody targeting PD-1 and CTLA-4, investigational code name only) in combination with mFOLFOX6 chemotherapy for several cycles. After completion of neoadjuvant therapy, patients will undergo total mesorectal excision (TME) when operable, or may be managed with a watch-and-wait strategy if a strict clinical complete response (cCR) is achieved per institutional criteria. Standard perioperative care and follow-up will be provided.
Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT)
QL1706 is an investigational bifunctional MabPair antibody that simultaneously targets PD-1 (IgG4) and CTLA-4 (IgG1). It is administered intravenously according to the study protocol during the neoadjuvant chemotherapy cycles. The use of QL1706 aims to enhance antitumor immunity in the pMMR/MSS rectal cancer setting, a population typically unresponsive to immune checkpoint blockade alone.
mFOLFOX6 is a standard oxaliplatin-based chemotherapy regimen composed of oxaliplatin, leucovorin, and 5-fluorouracil. It is administered in combination with QL1706 during the neoadjuvant phase as part of total neoadjuvant therapy (TNT). The regimen is modified to optimize tolerability while maintaining efficacy in locally advanced rectal cancer.
Short-course radiotherapy consists of a total dose of 25 Gy delivered in 5 fractions over one week to the pelvis. This approach is designed to rapidly downstage tumors, release tumor antigens, and prime the immune microenvironment for subsequent immunotherapy
Interventions
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Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT)
QL1706 is an investigational bifunctional MabPair antibody that simultaneously targets PD-1 (IgG4) and CTLA-4 (IgG1). It is administered intravenously according to the study protocol during the neoadjuvant chemotherapy cycles. The use of QL1706 aims to enhance antitumor immunity in the pMMR/MSS rectal cancer setting, a population typically unresponsive to immune checkpoint blockade alone.
mFOLFOX6 is a standard oxaliplatin-based chemotherapy regimen composed of oxaliplatin, leucovorin, and 5-fluorouracil. It is administered in combination with QL1706 during the neoadjuvant phase as part of total neoadjuvant therapy (TNT). The regimen is modified to optimize tolerability while maintaining efficacy in locally advanced rectal cancer.
Short-course radiotherapy consists of a total dose of 25 Gy delivered in 5 fractions over one week to the pelvis. This approach is designed to rapidly downstage tumors, release tumor antigens, and prime the immune microenvironment for subsequent immunotherapy
Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
75 Years
ALL
No
Sponsors
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Sun Yat-sen University
OTHER
Responsible Party
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Zhen-Hai Lu
Prof
Central Contacts
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References
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Other Identifiers
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B2025-431
Identifier Type: -
Identifier Source: org_study_id
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