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

University of Chinese Academy Sciences

Status and phase: Not yet enrolling; Phase 2

Conditions: Radiation; AK112; Rectal Cancer

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07162714

STAR

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Experimental arm

Experimental group

Description:

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.

Treatment:

Procedure: Surgery

Radiation: radiotherapy

Other: Non-operative Management

Drug: Ivonescimab (20mg/kg Q3W)