SCRT Followed by AK112 in pMMR/MSS Mid-low Rectal Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorZhejiang Cancer Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
radiotherapy
RadiationThe 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.
Ivonescimab (20mg/kg Q3W)
DrugThe 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.
Non-operative Management
Other interventionSubjects 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.
Surgery
Procedure/SurgeryFor patients who do not achieve cCR at the end of 6 cycles treatment of Ivonescimab, TME surgery is recommended.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Experimental armExperimental treatment 4 interventions
Trial outcomes
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).
Time frame
at the end of 6 cycles of AK112 treatment (each cycle is 21 days) or after surgerySecondary outcomes
1
Treatment - related adverse reactions
Number of Participants with Treatment - related adverse reactions according to CTCAE 5.0
Time frame
From enrollment to 6 months after the last administration of study treatment2
locoregional control rate
from the date of registration to the date of occurrence of locoregional recurrence, or death due to any cause.
Time frame
Up to 3 years after the last administration of study treatment3
disease-free survival rate
from the date of registration to the date of occurrence of any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause.
Time frame
Up to 3 years after the last administration of study treatment4
Overall survival rate
from the date of registration to the date of death from any cause.
Time frame
Up to 3 years after the last administration of study treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Zhejiang Cancer Hospital
Lead sponsor
Akeso
Collaborator
Source ClinicalTrials.gov