A Single-arm, Prospective, Phase II Clinical Study of Short-course Radiotherapy Followed by CAPOX and Ivonescimab for Locally Advanced Low-middle Rectal Cancer with a High Risk of Recurrence
Overview
- Phase
- Phase 2
- Intervention
- Ivonescimab (SMT112 or AK112) Injection
- Conditions
- Locally Advanced Rectal Cancer
- Sponsor
- The First Affiliated Hospital of Zhengzhou University
- Enrollment
- 40
- Primary Endpoint
- Complete response rate (CR, pCR plus cCR )
- Status
- Not Yet Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is a single-arm, prospective, phase II clinical study to evaluate the efficacy and safety of preoperative short-course radiotherapy combined with ivonescimab and chemotherapy + total mesorectal excision(TME) surgery in patients with advanced rectal cancer.
Detailed Description
Studies included a screening period (no more than 28 days after participants signed informed consent form to 28 days before first dose), treatment (receiving appropriate treatment until disease progression, intolerable toxicity, withdrawal of informed consent, death or study end, whichever occurs first), and follow-up (including safety follow-up and survival follow-up). Eligible subjects will receive short-course radiotherapy (SCRT), pelvic 25Gy/5f/1 week. 1-2 weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: ivonescimab 20 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 850-1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed). Patients can choose to enter the organ preservation observation; If the efficacy after preoperative chemoradiotherapy is evaluated as clinical complete remission (cCR) and the patient strongly refuses surgery, the patient should be informed of the risk of recurrence and ask the patient to sign a rejection of surgery. Medication safety is assessed and, depending on the severity of adverse events (AEs) and drug relevance, investigators will take steps to ensure subject safety. After surgery (or patients who strongly refuse surgery) there is a 30- and 90-day safety follow-up, and survival assessments are performed every 3 months to obtain survival information and collect new tumor treatment information until the death of the participant, withdrawal of informed consent, or the end of the study, whichever occurs first.
Investigators
Yugui Lian
Clinical Professor
The First Affiliated Hospital of Zhengzhou University
Eligibility Criteria
Inclusion Criteria
- •ECOG score of 0-1;
- •histologically or cytologically confirmed colorectal adenocarcinoma with non-distant metastasis
- •Tumor distance from anal verge ≦10cm
- •at least one high-risk criterion defined by pelvic MRI: cT stage \>T2 (tumor invades intrinsic muscularis propria by more than 5 mm); Extramural vascular invasion; cN2; Involvement of the rectal mesorectal fascia (tumor or lymph node ≤1mm from the rectal mesorectal fascia); Lateral lymph node short diameter ≥5mm
- •enough organ function
Exclusion Criteria
- •with known MSI-H or dMMR
- •Multiple primary adenocarcinomas
- •History of pelvic radiotherapy
- •Previous immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immunocellular therapy, and other treatments targeting the immune mechanism of the tumor.
Arms & Interventions
ivonescimab+chemotherapy
Local advanced rectal cancer with short-course radiotherapy followed by sequential chemotherapy and ivonescimab
Intervention: Ivonescimab (SMT112 or AK112) Injection
Outcomes
Primary Outcomes
Complete response rate (CR, pCR plus cCR )
Time Frame: pCR rate : within 1 week after surgery；cCR：12-13 weeks after radiotherapy ends
pathological complete response rate plus clinical complete response rate
Secondary Outcomes
- ORR(up to 2 years)
- 3-years DFS rate(From date of treatment until the date of first documented disease relapse or date of death from any cause, whichever came first about 3years.)
- 5-years OS rate(From date of treatment until date of death from any cause,about 5 years)
- Incidence and severity of adverse events (AEs)(up to 2 years)
- Tumor downstaging rate(up to 2 years)
- 2-year organ preservation observation rate(up to two years)
- surgical complication(30 days after surgery)