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Locally Advanced Rectal Cancer (LARC)Phase 2NCT07175636

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

A Phase 2 study testing Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT) in people with Locally Advanced Rectal Cancer (LARC) and Mismatch Repair-Proficient (pMMR) Rectal Cancer, run by Sun Yat-sen University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
No sites listed yet
Study dates
20 Sep 2025to 20 Sep 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 15Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Zhenhai Lu, MD contact

+862087343124

luzhh@sysucc.org.cn

About this study

Official title: A Multicenter, Prospective, Phase II Clinical Trial of Short-Course Radiotherapy Followed by QL1706 Plus mFOLFOX6 as Total Neoadjuvant Therapy for Patients With pMMR/MSS Locally Advanced Rectal Cancer

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.

Read more

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.

Being tested
Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT)
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT)Drug

    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

Study groups in NCT07175636
Study groupRoleWhat they receive
Short-Course Radiotherapy Followed by QL1706 Plus mFOLFOX6ExperimentalParticipants 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.
Receives: Drug: Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Complete Response (pCR) Rate

    The proportion of patients who achieve pathologic complete response, defined as the absence of viable tumor cells in both the resected primary rectal specimen and the resected lymph nodes (ypT0N0), as assessed by central pathology review.

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

Secondary outcomes (5)
  1. Clinical Complete Response (cCR) Rate

    The proportion of patients achieving clinical complete response, defined by endoscopy, pelvic MRI, and digital rectal examination showing no evidence of residual tumor, based on institutional criteria.

    Measured: At response evaluation after neoadjuvant therapy and before surgery (approximately 12-20 weeks after enrollment).

  2. Major Pathologic Response (MPR) Rate

    The proportion of patients with ≤10% residual viable tumor cells in the resected specimen.

    Measured: At the time of surgery following neoadjuvant therapy.

  3. R0 Resection Rate

    The proportion of patients who undergo curative resection with negative microscopic margins (R0).

    Measured: At the time of surgery

  4. Overall Survival (OS)

    Time from enrollment to death from any cause.

    Measured: Up to 3 years after treatment.

  5. Disease-Free Survival (DFS)

    Time from surgery (or start of treatment for patients managed non-operatively) to first documented recurrence, progression, or death from any cause.

    Measured: Up to 3 years after treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2025
  2. Study start20 Sep 2025 (estimated)
  3. Primary completion20 Sep 2026 (estimated)
  4. Study completion20 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07175636
Sponsor's protocol ID
B2025-431
Status last verified
Sep 2025
First submitted
9 Sep 2025
Last updated
16 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Xiao WW, Chen G, Gao YH, Lin JZ, Wu XJ, Luo HL, Lu ZH, Wang QX, Sun R, Cai PQ, Zhu CM, Liu M, Li JB, Wang YR, Jin Y, Wang F, Luo HT, Li CL, Pan ZZ, Xu RH. Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial. Cancer Cell. 2024 Sep 9;42(9):1570-1581.e4. doi: 10.1016/j.ccell.2024.07.004. Epub 2024 Aug 1.

    PubMed 39094560
  • Lin ZY, Zhang P, Chi P, Xiao Y, Xu XM, Zhang AM, Qiu XF, Wu JX, Yuan Y, Wang ZN, Qu XJ, Li X, Nie X, Yang M, Cai KL, Zhang WK, Huang Y, Sun Z, Hou ZG, Ma C, Cheng FZ, Tao KX, Zhang T. Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial. Ann Oncol. 2024 Oct;35(10):882-891. doi: 10.1016/j.annonc.2024.06.015. Epub 2024 Jul 2.

    PubMed 38964714
  • Fakih M, Sandhu J, Lim D, Li X, Li S, Wang C. Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2023 May 1;9(5):627-634. doi: 10.1001/jamaoncol.2022.7845.

    PubMed 36892833
  • Versluis JM, Long GV, Blank CU. Learning from clinical trials of neoadjuvant checkpoint blockade. Nat Med. 2020 Apr;26(4):475-484. doi: 10.1038/s41591-020-0829-0. Epub 2020 Apr 9.

    PubMed 32273608
  • Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 23;386(25):2363-2376. doi: 10.1056/NEJMoa2201445. Epub 2022 Jun 5.

    PubMed 35660797
  • Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020 Apr;26(4):566-576. doi: 10.1038/s41591-020-0805-8. Epub 2020 Apr 6.

    PubMed 32251400
  • Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM; Timing of Rectal Cancer Response to Chemoradiation Consortium. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011 Jul;254(1):97-102. doi: 10.1097/SLA.0b013e3182196e1f.

    PubMed 21494121
  • Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, Reidy-Lagunes DL, Gollub MJ, Shia J, Guillem JG, Temple LK, Paty PB, Saltz LB. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014 Feb 20;32(6):513-8. doi: 10.1200/JCO.2013.51.7904. Epub 2014 Jan 13.

    PubMed 24419115
  • Fernandez-Martos C, Pericay C, Aparicio J, Salud A, Safont M, Massuti B, Vera R, Escudero P, Maurel J, Marcuello E, Mengual JL, Saigi E, Estevan R, Mira M, Polo S, Hernandez A, Gallen M, Arias F, Serra J, Alonso V. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study. J Clin Oncol. 2010 Feb 10;28(5):859-65. doi: 10.1200/JCO.2009.25.8541. Epub 2010 Jan 11.

    PubMed 20065174
  • Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, Stadler ZK, Wu AJ, Weiser MR, Paty PB, Guillem JG, Nash GM, Temple LK, Garcia-Aguilar J, Saltz LB. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Compr Canc Netw. 2014 Apr;12(4):513-9. doi: 10.6004/jnccn.2014.0056.

    PubMed 24717570
  • Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavere P, Glanzmann C, Cellier P, Collette L; EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. doi: 10.1016/S1470-2045(13)70599-0. Epub 2014 Jan 17.

    PubMed 24440473
  • Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829.

    PubMed 16971718
  • Pucciarelli S, Del Bianco P, Efficace F, Serpentini S, Capirci C, De Paoli A, Amato A, Cuicchi D, Nitti D. Patient-reported outcomes after neoadjuvant chemoradiotherapy for rectal cancer: a multicenter prospective observational study. Ann Surg. 2011 Jan;253(1):71-7. doi: 10.1097/SLA.0b013e3181fcb856.

    PubMed 21135694
  • Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet. 2010 Mar 20;375(9719):1030-47. doi: 10.1016/S0140-6736(10)60353-4.

    PubMed 20304247
  • Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.

    PubMed 15496622

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Drug: QL1706 Drug: mFOLFOX6 Radiation: Short-Course Radiotherapy (SCRT) in people with Locally Advanced Rectal Cancer (LARC) and Mismatch Repair-Proficient (pMMR) Rectal Cancer, run by Sun Yat-sen University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhenhai Lu, MD (+862087343124, luzhh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (pCR) Rate (time frame: At the time of surgery following completion of total neoadjuvant therapy (approximately 16-24 weeks after enrollment).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07175636, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025.

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