SCRT Followed by AK112 in pMMR/MSS Mid-low Rectal Cancer

NCT07162714 | Not Yet Recruiting Phase 2

• 1 other identifier: STAR
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Objectives： Evaluate the complete response rate (CR rate) and safety of short - course radiotherapy combined with ivonesimab (AK112) in patients with pMMR/MSS mid - low rectal cancer. Secondary Objectives： Evaluate treatment - related toxic reactions, the quality of life, long - term prognosis (local control \[LC\], disease - free survival \[DFS\] and overall survival \[OS\]). Patients will : Receive Radiotherapy: Pelvic IMRT or VMAT, DT 25Gy/5Fx. One week after radiotherapy, begin treatment with Ivorsimab (AK112) at a dose of 20mg/kg by intravenous drip on day 1. One cycle is 21 days, and a total of 6 cycles are to be carried out. Evaluate the curative effect after 3 cycles of treatment. Patients with progressive disease (PD) will withdraw from the study, and other treatment plans will be adjusted in a timely manner. Patients with CR/PR/SD will continue treatment for another 3 cycles. Conduct a comprehensive assessment after 6 cycles of treatment. Patients who achieve cCR can choose the watch - and - wait approach. For patients who do not achieve cCR, TME surgery is recommended. Decide whether to perform adjuvant chemotherapy based on the postoperative pathological findings.

Conditions

Rectal Cancer; Radiation; AK112

Outcome Measures

Primary Outcomes (1)

• Complete remission rate (CR rate)

  including clinical complete response rate (cCR) and pathological complete response rate (pCR). pCR status is defined as the absence of resected speci mens with surviving tumour cells. cCR is defined as undetectable signs of tumour at least 4 weeks after TNT completion by clinical ex amination, including magnetic resonance imaging (MRI), endoscopy, digital rectal examination (DRE) and Positron Emission Tomography-Computed Tomography (PET-CT).

  at the end of 6 cycles of AK112 treatment (each cycle is 21 days) or after surgery

Secondary Outcomes (6)

• Treatment - related adverse reactions

  From enrollment to 6 months after the last administration of study treatment

• locoregional control rate

  Up to 3 years after the last administration of study treatment

• disease-free survival rate

  Up to 3 years after the last administration of study treatment

• Overall survival rate

  Up to 3 years after the last administration of study treatment

• Qol EORTC-C30 questionnaire

  From enrollment to 6 months after the last administration of study treatment

Study Arms (1)

Experimental arm

EXPERIMENTAL

The patients receive pelvic radiotherapy: Intensity-Modulated Radiation Therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with a total dose of 25 Gy delivered in 5 fractions. One week post-radiotherapy, treatment with Ivonescimab (AK112) was initiated at a dose of 20 mg/kg via intravenous infusion on Day 1 of each 21-day cycle, for a total of 6 cycles. Treatment response was assessed after 3 cycles. Patients with Progressive Disease (PD) were withdrawn from the study and promptly switched to alternative regimens. Patients achieving CR/PR/SD continued treatment for an additional 3 cycles.A comprehensive evaluation was conducted after completing 6 cycles. Patients achieving clinical Complete Response (cCR) were eligible for watchful waiting. For those not attaining cCR, Total Mesorectal Excision (TME) surgery was recommended. The need for adjuvant chemotherapy was subsequently determined based on postoperative pathological findings.

Radiation: radiotherapy; Drug: Ivonescimab (20mg/kg Q3W); Other: Non-operative Management; Procedure: Surgery

Interventions

radiotherapy RADIATION

The patients receive pelvic radiotherapy: Intensity-Modulated Radiation Therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with a total dose of 25 Gy delivered in 5 fractions. Radiotherapy is to start on day 1 and to finish on day 5.

Experimental arm

Ivonescimab (20mg/kg Q3W) DRUG

The first dose of vonescimab (AK112) was administered 1 week after the completion of radiotherapy. Ivonescimab (AK112) was initiated at a dose of 20 mg/kg via intravenous infusion on Day 1 of each 21-day cycle, for a total of 6 cycles.

Experimental arm

Non-operative Management OTHER

Subjects who achieve cCR after radiation and 6 cycles treatment of Ivonescimab can, after discussion with the local investigator, decline surgery and opt for a non-operative management.

Experimental arm

Surgery PROCEDURE

For patients who do not achieve cCR at the end of 6 cycles treatment of Ivonescimab, TME surgery is recommended.

Experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 75 years old;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1;
• 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;
• The lower border of the lesion is ≤ 7 cm from the anal verge as determined by fibrocolonoscopy or digital rectal examination;
• 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);
• Able to accept the treatment plan during the study period;
• Signed written informed consent.

You may not qualify if:

• 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.
• Prior immunotherapy for any indication or a history of severe hypersensitivity reactions to other monoclonal antibodies.
• 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.
• Immunosuppressive therapy following organ transplantation.
• History of other malignancies within the past 5 years (excluding adequately treated non-melanoma skin cancer or carcinoma in situ).
• Severe uncontrolled recurrent infections or other significant uncontrolled comorbidities.
• 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
• 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.
• Active bleeding or bleeding predisposition.
• Pregnancy or lactation.
• Hypersensitivity to any component of the investigational drug(s).

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Akeso: collaborator

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 7, 2025
• First Posted: September 9, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 9, 2025

Record last verified: 2025-09