Locally Advanced Colorectal CancerPhase 2NCT07691632
Serplulimab Plus Decitabine and CAPOX Before Surgery for Locally Advanced Colorectal Cancer
A Phase 2 study testing Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine) in people with Locally Advanced Colorectal Cancer and Colorectal Adenocarcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial summary
Title:A Single-Arm, Single-Center, Phase II Exploratory Study of Serplulimab Combined with Decitabine plus CAPOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer Background:Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Colorectal Cancer, Colorectal Adenocarcinoma
- What is being tested?
- Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 30 Jun 2026to 31 Dec 2027
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily signs written informed consent before screening.
- Male or female, aged 18 years or older.
- Has at least one measurable lesion according to RECIST version 1.1.
- ECOG performance status score of 0 to 1.
- Histologically or pathologically confirmed colorectal adenocarcinoma with no prior antitumor treatment, staged as cT3/cT4N+M0 locally advanced colorectal cancer according to the AJCC/UICC 8th edition based on contrast-enhanced CT or MRI, with colonoscopy and/or diagnostic laparoscopy if clinically indicated.
- Planned to undergo surgery after neoadjuvant therapy according to clinical staging.
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- Expected survival of more than 3 months.
- Adequate major organ function, meeting all of the following criteria:
- Hematology: neutrophil count ≥1.5 × 10^9/L, platelet count ≥100 × 10^9/L, hemoglobin ≥90 g/L, and white blood cell count ≥3.5 × 10^9/L, without blood transfusion, granulocyte colony-stimulating factor, or other hematopoietic growth factors within 14 days before screening.
- Hepatic function: ALT and AST ≤2.5 × upper limit of normal, and total bilirubin ≤1.5 × upper limit of normal, or ≤3 × upper limit of normal for patients with Gilbert syndrome.
- Renal function: serum creatinine ≤1.5 × upper limit of normal or creatinine clearance ≥60 mL/min.
- Coagulation function: activated partial thromboplastin time, international normalized ratio, and prothrombin time ≤1.5 × upper limit of normal.
Who cannot join
- Prior treatment with any antitumor therapy, including chemotherapy, radiotherapy, hormonal therapy, or molecular targeted therapy.
- Prior immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways.
- History of another malignancy within 5 years or concurrent malignancy, except cured carcinoma in situ of the cervix, non-melanoma skin cancer, or other malignancy treated with curative intent with no evidence of disease for at least 5 years.
- Pre-existing peripheral neuropathy of grade 2 or higher according to NCI-CTCAE version 5.0.
- Known active central nervous system metastasis and/or carcinomatous meningitis.
- History of severe hypersensitivity reaction to any component of a product or formulation similar to the study PD-1 antibody, or known severe hypersensitivity reaction to other monoclonal antibodies, oxaliplatin, capecitabine, or related compounds, defined as NCI-CTCAE version 5.0 grade 3 or higher.
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- Known history of hereditary bleeding disorder or coagulation disorder associated with bleeding risk.
- Major surgery within 4 weeks before enrollment.
- Has not recovered from complications of prior surgery to grade 1 or lower according to CTCAE version 5.0, except alopecia and fatigue.
- Requires immunosuppressive medication within 2 weeks before enrollment or during the study, except intranasal, inhaled, topical, or local steroid injections; systemic corticosteroids at physiological doses equivalent to prednisone ≤10 mg/day; or short-term use of steroids for prevention or treatment of non-autoimmune allergic conditions for no more than 7 days.
- Active autoimmune disease or history of autoimmune disease with potential recurrence.
- Known history of interstitial lung disease or non-infectious pneumonitis.
- Known history of active tuberculosis.
- History of human immunodeficiency virus infection, other acquired or congenital immunodeficiency disease, organ transplantation, or stem cell transplantation.
- Positive hepatitis B surface antigen with HBV DNA ≥10^4 copies/mL or ≥2000 IU/mL at screening, or active hepatitis C defined as positive HCV antibody with HCV RNA above the lower limit of detection.
- Active or uncontrolled infection requiring systemic treatment within 2 weeks before enrollment.
- Receipt of a live viral vaccine within 4 weeks before enrollment.
- Intestinal obstruction, inflammatory bowel disease, extensive intestinal resection with chronic diarrhea, Crohn's disease, ulcerative colitis, or chronic diarrhea.
- Breastfeeding, or planning pregnancy during treatment and within 6 months after completion of treatment.
- Unwillingness to use effective contraception during treatment and within 6 months after completion of treatment, including male participants capable of fathering a child, female participants, and their male partners.
- Any other condition that, in the investigator's judgment, may affect protocol compliance or assessment of study endpoints and makes the participant unsuitable for this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality
Rui Liu, 86+022-23340123, liurui9003@163.com
About this study
Official title: A Single-Arm, Single-Center, Phase II Exploratory Clinical Study of Serplulimab Combined With Decitabine Plus CAPOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer
Title:A Single-Arm, Single-Center, Phase II Exploratory Study of Serplulimab Combined with Decitabine plus CAPOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer Background:Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. Patients with locally advanced colorectal cancer remain at high risk of recurrence and distant metastasis after surgery. Although perioperative chemotherapy has improved clinical outcomes, the pathological complete response rate remains limited. Immune checkpoint inhibitors have shown remarkable efficacy in dMMR/MSI-H colorectal cancer; however, most pMMR/MSS tumors respond poorly to immunotherapy alone. Decitabine, a DNA methyltransferase inhibitor, may enhance tumor immunogenicity by promoting tumor antigen expression, improving antigen presentation, increasing immune cell infiltration, and reshaping the tumor immune microenvironment. CAPOX chemotherapy may further induce immunogenic cell death and enhance antitumor immune responses. Therefore, the combination of serplulimab, decitabine, and CAPOX may provide a synergistic neoadjuvant treatment strategy for locally advanced colorectal cancer.
Objective:This study aims to evaluate the efficacy and safety of serplulimab combined with decitabine plus CAPOX as neoadjuvant therapy for patients with locally advanced colorectal cancer. The primary endpoint is pathological complete response rate. Secondary endpoints include R0 resection rate, tumor downstaging, objective response rate, disease-free survival, and safety outcomes.
Read more
Methods:This is a prospective, single-center, single-arm, phase II exploratory clinical study. A total of 35 patients with previously untreated locally advanced colorectal adenocarcinoma will be enrolled. Eligible patients are adults aged ≥18 years with histologically or pathologically confirmed cT3/cT4N+M0 colorectal adenocarcinoma according to the AJCC/UICC 8th edition, at least one measurable lesion according to RECIST 1.1, ECOG performance status of 0-1, adequate organ function, and an expected survival of more than 3 months.
The study includes a safety lead-in stage and a dose-expansion stage. In the safety lead-in stage, decitabine dose escalation will follow a conventional 3+3 design, with two planned dose levels: 10 mg and 15 mg intravenously on Days 1-2 of each 3-week cycle. Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. The maximum tolerated dose or recommended phase II dose of decitabine will be determined based on dose-limiting toxicity.
In the dose-expansion stage, patients will receive serplulimab combined with decitabine and CAPOX for four cycles as neoadjuvant therapy. Patients without distant metastasis and considered suitable for surgery will undergo radical colorectal cancer resection 2-4 weeks after completion of neoadjuvant treatment. Postoperative adjuvant therapy will be determined by the investigator according to pathological findings and clinical practice.
Endpoints and Analysis:The primary endpoint is pathological complete response, defined as the absence of residual viable tumor cells in the primary tumor and resected lymph nodes after neoadjuvant therapy. Secondary endpoints include R0 resection rate, tumor downstaging rate, objective response rate assessed by RECIST 1.1, and disease-free survival. Safety assessments include adverse events, serious adverse events, immune-related adverse events, laboratory abnormalities, vital signs, 12-lead ECG, ECOG performance status, thyroid function, and physical examination findings. Adverse events will be graded according to NCI-CTCAE version 5.0.
Descriptive statistics will be used for analysis. Continuous variables will be summarized by mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarized by frequency and percentage. Time-to-event outcomes will be analyzed using the Kaplan-Meier method.
Expected Significance:This study will explore whether the combination of PD-1 blockade, epigenetic modulation, and CAPOX chemotherapy can improve pathological response while maintaining acceptable safety in locally advanced colorectal cancer. The results may provide preliminary evidence for a new neoadjuvant treatment strategy and support future multicenter clinical studies.
- Being tested
- Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine)Drug
Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. Decitabine will be administered intravenously on Days 1-2 of each 3-week cycle. In the safety lead-in stage, decitabine dose escalation will follow a 3+3 design, with planned dose levels of 10 mg and 15 mg to determine the MTD/RP2D. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. Patients will receive 4 cycles of neoadjuvant treatment before radical colorectal cancer surgery if eligible.
| Study group | Role | What they receive |
|---|---|---|
| Serplulimab plus Decitabine and CAPOX(Oxaliplatin + Capecitabine) | Experimental | Patients will receive serplulimab combined with decitabine and CAPOX as neoadjuvant therapy. Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. Decitabine will be administered intravenously on Days 1-2 of each 3-week cycle, with dose escalation in the safety lead-in stage from 10 mg to 15 mg using a 3+3 design to determine the MTD/RP2D. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. Patients will receive 4 cycles of neoadjuvant treatment, followed by radical colorectal cancer surgery 2-4 weeks after completion of treatment if eligible. Postoperative adjuvant therapy will be determined by the investigator. Receives: Drug: Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response Rate
Pathological complete response rate is defined as the proportion of participants with no residual viable tumor cells in the primary tumor and resected lymph nodes in surgical specimens after neoadjuvant therapy.
Measured: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose
Secondary outcomes (5)
R0 Resection Rate
R0 resection rate is defined as the proportion of participants who undergo complete tumor resection with microscopically negative surgical margins and no residual tumor.
Measured: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose
Tumor Downstaging Rate
Tumor downstaging rate is defined as the proportion of participants with any reduction in pathological T stage or N stage after neoadjuvant therapy compared with baseline clinical staging.
Measured: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose
Objective Response Rate
Objective response rate is defined as the proportion of participants who achieve complete response or partial response according to RECIST version 1.1.
Measured: Every 3 weeks during neoadjuvant therapy, up to approximately 12 weeks after the first dose
Disease-Free Survival
Disease-free survival is defined as the time from enrollment to local or distant tumor recurrence or death from any cause, whichever occurs first. Disease-free survival will be analyzed only in participants who undergo R0 resection.
Measured: Up to approximately 24 months after enrollment
Incidence and Severity of Adverse Events
Safety will be assessed by the incidence, type, severity, duration, and relationship to study treatment of adverse events and serious adverse events. Safety assessments include laboratory abnormalities, vital signs, 12-lead electrocardiogram, ECOG performance status, thyroid function, and physical examination findings. Adverse events will be graded according to NCI-CTCAE version 5.0.
Measured: From the first dose of study treatment through 28 days after the last dose, up to approximately 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2026
- Study start30 Jun 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07691632
- Sponsor's protocol ID
- HLX10IIT462
- Status last verified
- Jun 2026
- First submitted
- 1 Jul 2026
- Last updated
- 9 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
张剑威，邓艳红. 微卫星稳定或错配修复正常结直肠癌的新辅助免疫治疗［J］.中华胃肠外科杂志，2022, 25(3):193-198.
Hasegawa J, Nishimura J, Mizushima T, Miyake Y, Kim HM, Takemoto H, Tamagawa H, Noura S, Fujii M, Fujie Y, Kato T, Miwa H, Takemasa I, Ikeda M, Yamamoto H, Sekimoto M, Nezu R, Doki Y, Mori M. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol. 2014 May;73(5):1079-87. doi: 10.1007/s00280-014-2417-9. Epub 2014 Mar 5.
PubMed 24595805Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, Cai K, Nie X, Wang J, Liu J, Liu H, Zhang W, Gao J, Wu C, Wang L, Fan J, Zhang L, Wang Z, Hou Z, Ma C, Yang K, Wu G, Tao K, Zhang T. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021 Nov;9(11):e003554. doi: 10.1136/jitc-2021-003554.
PubMed 34725214Bando H, Tsukada Y, Inamori K, Togashi Y, Koyama S, Kotani D, Fukuoka S, Yuki S, Komatsu Y, Homma S, Taketomi A, Uemura M, Kato T, Fukui M, Wakabayashi M, Nakamura N, Kojima M, Kawachi H, Kirsch R, Yoshida T, Suzuki Y, Sato A, Nishikawa H, Ito M, Yoshino T. Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer. Clin Cancer Res. 2022 Mar 15;28(6):1136-1146. doi: 10.1158/1078-0432.CCR-21-3213.
PubMed 35063964Tanaka S, Hosokawa M, Ueda K, Iwakawa S. Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells. Biol Pharm Bull. 2015;38(9):1272-9. doi: 10.1248/bpb.b15-00129. Epub 2015 Jul 15.
PubMed 26179333Taib N, Merhi M, Inchakalody V, Mestiri S, Hydrose S, Makni-Maalej K, Raza A, Sahir F, Azizi F, Nizamuddin PB, Fernandes Q, Yoosuf ZSKM, Almoghrabi S, Al-Zaidan L, Shablak A, Uddin S, Maccalli C, Al Homsi MU, Dermime S. Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy. J Transl Med. 2023 Mar 31;21(1):235. doi: 10.1186/s12967-023-04073-y.
PubMed 37004094Huang KC, Chiang SF, Chen WT, Chen TW, Hu CH, Yang PC, Ke TW, Chao KSC. Decitabine Augments Chemotherapy-Induced PD-L1 Upregulation for PD-L1 Blockade in Colorectal Cancer. Cancers (Basel). 2020 Feb 17;12(2):462. doi: 10.3390/cancers12020462.
PubMed 32079180Yu G, Wu Y, Wang W, Xu J, Lv X, Cao X, Wan T. Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment. Cell Mol Immunol. 2019 Apr;16(4):401-409. doi: 10.1038/s41423-018-0026-y. Epub 2018 Apr 5.
PubMed 29622799Anguille S, Smits EL, Bryant C, Van Acker HH, Goossens H, Lion E, Fromm PD, Hart DN, Van Tendeloo VF, Berneman ZN. Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy. Pharmacol Rev. 2015 Oct;67(4):731-53. doi: 10.1124/pr.114.009456.
PubMed 26240218Harris JE, Ryan L, Hoover HC Jr, Stuart RK, Oken MM, Benson AB 3rd, Mansour E, Haller DG, Manola J, Hanna MG Jr. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Oncol. 2000 Jan;18(1):148-57. doi: 10.1200/JCO.2000.18.1.148.
PubMed 10623705Wang Y, Deng W, Li N, Neri S, Sharma A, Jiang W, Lin SH. Combining Immunotherapy and Radiotherapy for Cancer Treatment: Current Challenges and Future Directions. Front Pharmacol. 2018 Mar 5;9:185. doi: 10.3389/fphar.2018.00185. eCollection 2018.
PubMed 29556198Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022 May 20;40(15):1681-1692. doi: 10.1200/JCO.21.01667. Epub 2022 Mar 9.
PubMed 35263150Takei S, Tanaka Y, Lin YT, Koyama S, Fukuoka S, Hara H, Nakamura Y, Kuboki Y, Kotani D, Kojima T, Bando H, Mishima S, Ueno T, Kojima S, Wakabayashi M, Sakamoto N, Kojima M, Kuwata T, Yoshino T, Nishikawa H, Mano H, Endo I, Shitara K, Kawazoe A. Multiomic molecular characterization of the response to combination immunotherapy in MSS/pMMR metastatic colorectal cancer. J Immunother Cancer. 2024 Feb 8;12(2):e008210. doi: 10.1136/jitc-2023-008210.
PubMed 38336371Yu B, Kang J, Lei H, Li Z, Yang H, Zhang M. Immunotherapy for colorectal cancer. Front Immunol. 2024 Aug 21;15:1433315. doi: 10.3389/fimmu.2024.1433315. eCollection 2024.
PubMed 39238638Hu H, Zhang J, Li Y, Wang X, Wang Z, Wang H, Kang L, Liu P, Lan P, Wu X, Zhen Y, Pei H, Huang Z, Zhang H, Chen W, Zeng Y, Lai J, Wei H, Huang X, Chen J, Chen J, Tao K, Xu Q, Peng X, Liang J, Cai G, Ding K, Ding Z, Hu M, Zhang W, Tang B, Hong C, Cao J, Huang Z, Cao W, Li F, Wang X, Wang C, Huang Y, Zhao Y, Cai Y, Ling J, Xie X, Wu Z, Shi L, Ling L, Liu H, Wang J, Huang M, Deng Y; OPTICAL study group. Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial. J Clin Oncol. 2024 Sep 1;42(25):2978-2988. doi: 10.1200/JCO.23.01889. Epub 2024 Apr 2.
PubMed 38564700
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Single-Center, Phase II Exploratory Clinical Study of Serplulimab Combined With Decitabine Plus CAPOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07691632
- Acronym / sponsor ID
- HLX10IIT462
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 30 Jun 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 9 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Title:A Single-Arm, Single-Center, Phase II Exploratory Study of Serplulimab Combined with Decitabine plus CAPOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer Background:Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. Patients with locally advanced colorectal cancer remain at high risk of recurrence and distant metastasis after surgery. Although perioperative chemotherapy has improved clinical outcomes, the pathological complete response rate remains limited. Immune checkpoint inhibitors have shown remarkable efficacy in dMMR/MSI-H colorectal cancer; however, most pMMR/MSS tumors respond poorly to immunotherapy alone. Decitabine, a DNA methyltransferase inhibitor, may enhance tumor immunogenicity by promoting tumor antigen expression, improving antigen presentation, increasing immune cell infiltration, and reshaping the tumor immune microenvironment. CAPOX chemotherapy may further induce immunogenic cell death and enhance antitumor immune responses. Therefore, the combination of serplulimab, decitabine, and CAPOX may provide a synergistic neoadjuvant treatment strategy for locally advanced colorectal cancer.
Objective:This study aims to evaluate the efficacy and safety of serplulimab combined with decitabine plus CAPOX as neoadjuvant therapy for patients with locally advanced colorectal cancer. The primary endpoint is pathological complete response rate. Secondary endpoints include R0 resection rate, tumor downstaging, objective response rate, disease-free survival, and safety outcomes.
Methods:This is a prospective, single-center, single-arm, phase II exploratory clinical study. A total of 35 patients with previously untreated locally advanced colorectal adenocarcinoma will be enrolled. Eligible patients are adults aged ≥18 years with histologically or pathologically confirmed cT3/cT4N+M0 colorectal adenocarcinoma according to the AJCC/UICC 8th edition, at least one measurable lesion according to RECIST 1.1, ECOG performance status of 0-1, adequate organ function, and an expected survival of more than 3 months.
The study includes a safety lead-in stage and a dose-expansion stage. In the safety lead-in stage, decitabine dose escalation will follow a conventional 3+3 design, with two planned dose levels: 10 mg and 15 mg intravenously on Days 1-2 of each 3-week cycle. Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. The maximum tolerated dose or recommended phase II dose of decitabine will be determined based on dose-limiting toxicity.
In the dose-expansion stage, patients will receive serplulimab combined with decitabine and CAPOX for four cycles as neoadjuvant therapy. Patients without distant metastasis and considered suitable for surgery will undergo radical colorectal cancer resection 2-4 weeks after completion of neoadjuvant treatment. Postoperative adjuvant therapy will be determined by the investigator according to pathological findings and clinical practice.
Endpoints and Analysis:The primary endpoint is pathological complete response, defined as the absence of residual viable tumor cells in the primary tumor and resected lymph nodes after neoadjuvant therapy. Secondary endpoints include R0 resection rate, tumor downstaging rate, objective response rate assessed by RECIST 1.1, and disease-free survival. Safety assessments include adverse events, serious adverse events, immune-related adverse events, laboratory abnormalities, vital signs, 12-lead ECG, ECOG performance status, thyroid function, and physical examination findings. Adverse events will be graded according to NCI-CTCAE version 5.0.
Descriptive statistics will be used for analysis. Continuous variables will be summarized by mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarized by frequency and percentage. Time-to-event outcomes will be analyzed using the Kaplan-Meier method.
Expected Significance:This study will explore whether the combination of PD-1 blockade, epigenetic modulation, and CAPOX chemotherapy can improve pathological response while maintaining acceptable safety in locally advanced colorectal cancer. The results may provide preliminary evidence for a new neoadjuvant treatment strategy and support future multicenter clinical studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Serplulimab plus Decitabine and CAPOX(Oxaliplatin + Capecitabine) | Experimental | Drug: Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine)Patients will receive serplulimab combined with decitabine and CAPOX as neoadjuvant therapy. Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. Decitabine will be administered intravenously on Days 1-2 of each 3-week cycle, with dose escalation in the safety lead-in stage from 10 mg to 15 mg using a 3+3 design to determine the MTD/RP2D. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. Patients will receive 4 cycles of neoadjuvant treatment, followed by radical colorectal cancer surgery 2-4 weeks after completion of treatment if eligible. Postoperative adjuvant therapy will be determined by the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Voluntarily signs written informed consent before screening.
- Male or female, aged 18 years or older.
- Has at least one measurable lesion according to RECIST version 1.1.
- ECOG performance status score of 0 to 1.
- Histologically or pathologically confirmed colorectal adenocarcinoma with no prior antitumor treatment, staged as cT3/cT4N+M0 locally advanced colorectal cancer according to the AJCC/UICC 8th edition based on contrast-enhanced CT or MRI, with colonoscopy and/or diagnostic laparoscopy if clinically indicated.
Key exclusion criteria (21 listed)
- Prior treatment with any antitumor therapy, including chemotherapy, radiotherapy, hormonal therapy, or molecular targeted therapy.
- Prior immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways.
- History of another malignancy within 5 years or concurrent malignancy, except cured carcinoma in situ of the cervix, non-melanoma skin cancer, or other malignancy treated with curative intent with no evidence of disease for at least 5 years.
- Pre-existing peripheral neuropathy of grade 2 or higher according to NCI-CTCAE version 5.0.
- Known active central nervous system metastasis and/or carcinomatous meningitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine)Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. Decitabine will be administered intravenously on Days 1-2 of each 3-week cycle. In the safety lead-in stage, decitabine dose escalation will follow a 3+3 design, with planned dose levels of 10 mg and 15 mg to determine the MTD/RP2D. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. Patients will receive 4 cycles of neoadjuvant treatment before radical colorectal cancer surgery if eligible. | Drug | Serplulimab plus Decitabine and CAPOX(Oxaliplatin + Capecitabine) |
Primary outcome
Pathological Complete Response Rate
Time frame: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose
Pathological complete response rate is defined as the proportion of participants with no residual viable tumor cells in the primary tumor and resected lymph nodes in surgical specimens after neoadjuvant therapy.
5 secondary outcomes
R0 Resection Rate
Time frame: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose
Tumor Downstaging Rate
Time frame: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose
Objective Response Rate
Time frame: Every 3 weeks during neoadjuvant therapy, up to approximately 12 weeks after the first dose
Disease-Free Survival
Time frame: Up to approximately 24 months after enrollment
Incidence and Severity of Adverse Events
Time frame: From the first dose of study treatment through 28 days after the last dose, up to approximately 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Results publication张剑威，邓艳红. 微卫星稳定或错配修复正常结直肠癌的新辅助免疫治疗［J］.中华胃肠外科杂志，2022, 25(3):193-198.
- Results publication: PubMed 24595805Hasegawa J, Nishimura J, Mizushima T, Miyake Y, Kim HM, Takemoto H, Tamagawa H, Noura S, Fujii M, Fujie Y, Kato T, Miwa H, Takemasa I, Ikeda M, Yamamoto H, Sekimoto M, Nezu R, Doki Y, Mori M. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol. 2014 May;73(5):1079-87. doi: 10.1007/s00280-014-2417-9. Epub 2014 Mar 5.
- Results publication: PubMed 34725214Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, Cai K, Nie X, Wang J, Liu J, Liu H, Zhang W, Gao J, Wu C, Wang L, Fan J, Zhang L, Wang Z, Hou Z, Ma C, Yang K, Wu G, Tao K, Zhang T. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021 Nov;9(11):e003554. doi: 10.1136/jitc-2021-003554.
- Results publication: PubMed 35063964Bando H, Tsukada Y, Inamori K, Togashi Y, Koyama S, Kotani D, Fukuoka S, Yuki S, Komatsu Y, Homma S, Taketomi A, Uemura M, Kato T, Fukui M, Wakabayashi M, Nakamura N, Kojima M, Kawachi H, Kirsch R, Yoshida T, Suzuki Y, Sato A, Nishikawa H, Ito M, Yoshino T. Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer. Clin Cancer Res. 2022 Mar 15;28(6):1136-1146. doi: 10.1158/1078-0432.CCR-21-3213.
- Results publication: PubMed 26179333Tanaka S, Hosokawa M, Ueda K, Iwakawa S. Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells. Biol Pharm Bull. 2015;38(9):1272-9. doi: 10.1248/bpb.b15-00129. Epub 2015 Jul 15.
- Results publication: PubMed 37004094Taib N, Merhi M, Inchakalody V, Mestiri S, Hydrose S, Makni-Maalej K, Raza A, Sahir F, Azizi F, Nizamuddin PB, Fernandes Q, Yoosuf ZSKM, Almoghrabi S, Al-Zaidan L, Shablak A, Uddin S, Maccalli C, Al Homsi MU, Dermime S. Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy. J Transl Med. 2023 Mar 31;21(1):235. doi: 10.1186/s12967-023-04073-y.
- Results publication: PubMed 32079180Huang KC, Chiang SF, Chen WT, Chen TW, Hu CH, Yang PC, Ke TW, Chao KSC. Decitabine Augments Chemotherapy-Induced PD-L1 Upregulation for PD-L1 Blockade in Colorectal Cancer. Cancers (Basel). 2020 Feb 17;12(2):462. doi: 10.3390/cancers12020462.
- Results publication: PubMed 29622799Yu G, Wu Y, Wang W, Xu J, Lv X, Cao X, Wan T. Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment. Cell Mol Immunol. 2019 Apr;16(4):401-409. doi: 10.1038/s41423-018-0026-y. Epub 2018 Apr 5.
- Results publication: PubMed 26240218Anguille S, Smits EL, Bryant C, Van Acker HH, Goossens H, Lion E, Fromm PD, Hart DN, Van Tendeloo VF, Berneman ZN. Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy. Pharmacol Rev. 2015 Oct;67(4):731-53. doi: 10.1124/pr.114.009456.
- Results publication: PubMed 10623705Harris JE, Ryan L, Hoover HC Jr, Stuart RK, Oken MM, Benson AB 3rd, Mansour E, Haller DG, Manola J, Hanna MG Jr. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Oncol. 2000 Jan;18(1):148-57. doi: 10.1200/JCO.2000.18.1.148.
- Results publication: PubMed 29556198Wang Y, Deng W, Li N, Neri S, Sharma A, Jiang W, Lin SH. Combining Immunotherapy and Radiotherapy for Cancer Treatment: Current Challenges and Future Directions. Front Pharmacol. 2018 Mar 5;9:185. doi: 10.3389/fphar.2018.00185. eCollection 2018.
- Results publication: PubMed 35263150Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022 May 20;40(15):1681-1692. doi: 10.1200/JCO.21.01667. Epub 2022 Mar 9.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Serplulimab + Decitabine + CAPOX (Oxaliplatin + Capecitabine) in people with Locally Advanced Colorectal Cancer and Colorectal Adenocarcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
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 12 inclusion and 21 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 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Rui Liu (86+022-23340123, liurui9003@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Complete Response Rate (time frame: 2 to 4 weeks after completion of four cycles of neoadjuvant therapy, approximately 14 to 16 weeks after the first dose). 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 NCT07691632, which also lists 20 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 9 Jul 2026.