Short-course Radiotherapy Followed by CAPOX and Ivonescimab for Locally Advanced Rectal Cancer

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: Ivonescimab (SMT112 or AK112) Injection

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yugui Lian, M.D; Phone Number: +86 0371-66279076; Email: fcclianyg@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ivonescimab+chemotherapy; Local advanced rectal cancer with short-course radiotherapy followed by sequential chemotherapy and ivonescimab

Drug: Ivonescimab (SMT112 or AK112) Injection; Eligible subjects will receive short-course radiotherapy (SCRT), 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: AK112 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CR, pCR plus cCR )	pathological complete response rate plus clinical complete response rate	pCR rate : within 1 week after surgery；cCR：12-13 weeks after radiotherapy ends

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
ORR	objective response rate	up to 2 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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): January 20, 2025
• Primary Completion (Estimated): December 20, 2027
• Study Completion (Estimated): December 20, 2031

Study Registration Dates

• First Submitted: December 21, 2024
• First Submitted That Met QC Criteria: January 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: 2024-KY-1578-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No