Short-course radiotherapy followed by AK112 in mid-low rectal cancer with pMMR/MSS

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 interventional study explores combining a 25 Gy, 5-fraction pelvic radiotherapy with six cycles of AK112 given every 3 weeks to patients with pMMR/MSS mid-low rectal cancer. The primary goal is to determine the complete response rate and assess safety; secondary goals include treatment-related toxicity, quality of life, and long-term outcomes such as local control, disease-free survival, and overall survival. Treatment decisions during the trial are guided by response after cycle 3, with continuation for those not progressing. Radiation is followed by AK112 initiation one week later, and evaluation occurs after 6 cycles to determine curative status. Non-operative management and potential surgical options may be considered based on response.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Aged between 18 and 75 years old;
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1;
3. Histopathologically confirmed rectal adenocarcinoma, without any prior anti - tumor treatment; The status of MMR/MSI is detected by IHC/PCR in pathological biopsy to clarify that the patient's classification is pMMR/MSS;
4. The lower border of the lesion is ≤ 7 cm from the anal verge as determined by fibrocolonoscopy or digital rectal examination;
5. Baseline magnetic resonance staging is cT2 - 4 and/or N+, excluding any of cT4b, N2, positive mesorectal fascia (MRF+), extramural venous invasion (EMVI+), lateral lymph node metastasis, and distant metastasis (according to the 8th edition of the AJCC Cancer Staging Manual);
6. Able to accept the treatment plan during the study period;
7. Signed written informed consent.

Exclusion Criteria:

1. Uncontrolled epilepsy, history of central nervous system disorders or psychiatric conditions that, in the investigator's judgment, may interfere with the ability to provide informed consent or affect compliance with oral medication.
2. Prior immunotherapy for any indication or a history of severe hypersensitivity reactions to other monoclonal antibodies.
3. Clinically significant active cardiac disease, including symptomatic coronary artery disease, congestive heart failure (New York Heart Association \[NYHA\] Class II or higher), severe arrhythmias requiring medication, or a history of myocardial infarction within the past 12 months.
4. Immunosuppressive therapy following organ transplantation.
5. History of other malignancies within the past 5 years (excluding adequately treated non-melanoma skin cancer or carcinoma in situ).
6. Severe uncontrolled recurrent infections or other significant uncontrolled comorbidities.
7. Baseline laboratory values failing to meet the following criteria:Hemoglobin ≥80 g/L; Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelets ≥100×10\^9/L; ALT/AST ≤2.5×upper limit of normal (ULN); Alkaline phosphatase (ALP) ≤2.5×ULN; Total bilirubin \<1.5×ULN; Serum creatinine \<1×ULN
8. Active gastrointestinal diseases (e.g., gastric/duodenal ulcers, ulcerative colitis), unresected tumors with active bleeding, or other conditions deemed by the investigator to pose risks of gastrointestinal bleeding or perforation.
9. Active bleeding or bleeding predisposition.
10. Pregnancy or lactation.
11. Hypersensitivity to any component of the investigational drug(s).

Where it's running

• Zhejiang cancer hosptial
  Hangzhou, Zhejiang, China Recruiting

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.