Advanced RAS-Mutated Colorectal Cancer With Liver Metastases (CRLM)
Conditions
Brief summary
This single-arm phase II trial enrolls patients with RAS-mutant, microsatellite-stable (MSS) unresectable colorectal cancer liver metastases receiving first-line treatment with Retlirafusp alfa combined with XELOX (capecitabine plus oxaliplatin) and bevacizumab. The primary endpoint is objective response rate (ORR). A total of 46 patients will be enrolled, and the study is expected to be completed between 2026 and 2029.
Interventions
DRUGRetlirafusp alfa+XELOX+Bevacizumab Treatment
Enrolled subjects received Retlirafusp alfa injection (1800 mg, IV, Day 1, every 3 weeks) + bevacizumab (7.5 mg/kg, IV, Day 1, every 3 weeks) plus XELOX (capecitabine 1,000 mg/m², oral, twice daily, Days 1-14; and oxaliplatin 130 mg/m², IV, Day 1, every 3 weeks). Oxaliplatin was discontinued after a maximum of 8 cycles, while the other agents were continued, marking the transition to the maintenance phase. Immunotherapy was administered for no more than 2 years.
Sponsors
Dai, Guanghai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18-75 years; 2. Unresectable colorectal adenocarcinoma confirmed by histopathology or cytology; 3. MSS/pMMR; 4. RAS-mutant; 5. ECOG PS score of 0-1; 6. No prior systemic treatment; 7. At least one measurable liver metastasis; 8. Expected survival of ≥3 months; 9. Normal function of major organs; no severe abnormalities in hematological, cardiac, pulmonary, hepatic, renal, or bone marrow function; and no immunodeficiency. Laboratory test results must meet the following requirements: ① Hemoglobin (Hb) ≥90 g/L; ② White blood cell (WBC) count ≥ 3.0 × 10⁹/L; neutrophil count (NEUT) ≥ 1.5 × 10⁹/L; ③ Platelet (PLT) count ≥ 100 × 10⁹/L ④ Renal function (serum creatinine, sCr) ≤ 1.5 times the upper limit of normal (ULN); ⑤ Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); 10. Participants voluntarily enroll in this study, sign an informed consent form, demonstrate good compliance, and cooperate with follow-up; 11. The investigator believes the participant may benefit from treatment.
Exclusion criteria
1. History of or concurrent other malignant tumors, excluding cured basal cell carcinoma of the skin and cervical carcinoma in situ; 2. History of severe cardiovascular disease, such as congestive heart failure (New York Heart Association Class III-IV), myocardial infarction within the past 6 months, unstable angina, or severe arrhythmias; 3. Presence of active infections (e.g., sepsis, active tuberculosis) or uncontrolled autoimmune diseases; 4. History of severe gastrointestinal diseases, such as active peptic ulcers, intestinal obstruction, or gastrointestinal bleeding, which may affect drug absorption or increase treatment-related risks; 5. History of active cirrhosis, uncontrolled comorbidities, chronic myopathy, active hepatitis, or persistent unexplained elevation of serum transaminases; 6. Coagulation disorders with a tendency to bleed (must meet the following criterion 14 days prior to enrollment: INR within the normal range without the use of anticoagulants); Subjects receiving treatment with anticoagulants or vitamin K antagonists, such as warfarin, heparin, or their analogs; low-dose warfarin (1 mg orally once daily) or low-dose aspirin (daily dose not exceeding 100 mg) is permitted for prophylactic purposes, provided that the International Normalized Ratio (INR) of prothrombin time is ≤ 1.5; 7. Allergy to or contraindications for the study drug; 8. Pregnant or breastfeeding women, or patients planning to become pregnant during the study or within 6 months after the study ends and who are not using effective contraception; 9. Presence of other serious, uncontrolled medical conditions or psychiatric disorders that may affect the patient's ability to participate in the study or undergo evaluation; 10. History of thyroid dysfunction, where thyroid function cannot be maintained within the normal range even with medication; 11. Patients with severe, uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg despite antihypertensive medication), or a history of hypertensive crisis or hypertensive encephalopathy; 12. Patients with a history of severe bleeding or a high risk of bleeding, including but not limited to: clinically significant bleeding (e.g., ≥ Grade 2 gastrointestinal bleeding) occurring within 3 months prior to the first administration of the study drug; active hemoptysis (hemoptysis volume ≥ half a teaspoon, approximately 2.5 mL of fresh blood, within the past month); imaging evidence of tumor invasion of major blood vessels; or an untreated coagulation disorder (however, patients receiving a stable dose of anticoagulant therapy with an INR within the therapeutic range may be considered for enrollment following the investigator's assessment); 13. Patients who have experienced the following arterial or venous thromboembolic events within 6 months prior to the first administration of the study drug: cerebrovascular accident (including ischemic stroke and transient ischemic attack), myocardial infarction, acute coronary syndrome, uncontrolled deep vein thrombosis, or pulmonary embolism (superficial venous thrombosis, such as PICC-related upper extremity venous thrombosis, may be considered on a case-by-case basis if assessed by the investigator as low risk); 14. Patients deemed unsuitable for inclusion in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 24 months | The proportion of patients with a confirmed complete response or partial response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progress-free Survival(PFS) | 24 months | The time from enrollment until tumor progression or death from any cause, whichever occurred first |
| Overall Survival (OS) | 24 months | The time from randomization to death from any reason |
| Incidence of Adverse Events | 90 days | Incidence of Adverse Events According to the CTCAE 6.0 |
Countries
China
Contacts
CONTACTGuanghai Dai, MD
Outcome results
None listed