Anlotinib plus sintilimab as first treatment for advanced colorectal cancer without liver metastases

Phase II Study of Anlotinib Combined With Sintilimab as First-line Treatment for Advanced Non-liver Metastatic Colorectal Cancer

This study will see if taking anlotinib together with sintilimab as the first treatment helps adults with advanced colorectal cancer that has spread outside the liver who cannot or choose not to have standard chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (other)
• Drugs / interventions: anlotinib, chemotherapy, radiation, prednisone, sintilimab
• Locations: 1 site (Shanghai)
• Trial ID: NCT07398326 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives adults with histologically confirmed advanced colorectal adenocarcinoma and non-hepatic metastases a combination of oral anlotinib and intravenous sintilimab as first-line therapy. Eligible patients are chemotherapy-naïve or had relapse ≥12 months after adjuvant therapy, must have at least one measurable lesion by RECIST 1.1, and an ECOG performance status of 0–1. The study will monitor tumor response, progression-free survival, and safety with regular RECIST assessments, imaging, and laboratory testing. Prior local radiotherapy is permitted if completed ≥3 weeks before treatment and lesions used for response assessment are outside the radiation field.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed advanced colorectal adenocarcinoma with non-hepatic metastases, measurable disease, ECOG 0–1, life expectancy ≥12 weeks, who are systemic therapy–naïve or relapsed ≥12 months after adjuvant therapy, and who refuse chemotherapy.

Not a fit: Patients with liver-only metastases, poor performance status (ECOG ≥2), recent systemic therapy, or contraindications to immunotherapy or tyrosine kinase inhibitors are unlikely to benefit.

Why it matters

Potential benefit: If successful, the regimen could offer an effective, lower-toxicity first-line option for patients with advanced colorectal cancer who cannot or choose not to receive standard chemotherapy.

How similar studies have performed: Combinations of antiangiogenic TKIs and PD-1 inhibitors have shown promising activity in other tumor types and early colorectal cancer cohorts, but robust evidence specifically for anlotinib plus sintilimab in non-liver metastatic CRC is limited.

Eligibility criteria

Inclusion Criteria:

* Patients with histologically or cytologically confirmed advanced colorectal adenocarcinoma.
* Patients with non-hepatic metastases who explicitly refuse chemotherapy.
* Patients who have not received prior systemic therapy, or those with metastasis or recurrence occurring ≥12 months after completion of adjuvant therapy.
* At least one measurable lesion according to RECIST 1.1 criteria.
* Prior local radiotherapy is permitted if completed at least 3 weeks before the first study drug administration; however, lesions used for RECIST evaluation must be outside the radiation field.
* Age ≥18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life expectancy ≥12 weeks.
* Ability to understand and voluntarily provide written informed consent.
* For women of childbearing potential, a negative pregnancy test within 7 days prior to treatment initiation. Both patients and their partners must agree to use effective contraception during the study period.

Exclusion Criteria:

* Patients who have undergone major surgery or sustained severe trauma within 4 weeks prior to the first dose of the study drug.
* Patients with a history of hypersensitivity to any component of the study regimen.
* Patients who are planning to conceive, are pregnant.
* Patients with brain metastases who are unable to accurately describe their symptoms or condition.
* Patients with a history of autoimmune diseases or organ transplantation.
* Use of immunosuppressive medications within 2 weeks prior to the initiation of study treatment (excluding inhaled corticosteroids, or physiological replacement doses of steroids equivalent to ≤10 mg/day of prednisone).
* Administration of a live attenuated vaccine within 4 weeks prior to the start of study treatment or planned vaccination during the study period.
* Prior treatment with anlotinib, anti-PD-1/PD-L1 monoclonal antibodies, or any other therapy targeting T-cell co-stimulation or immune checkpoint pathways.
* History of any of the following within 6 months before starting study treatment: myocardial infarction, severe/unstable angina, congestive heart failure of New York Heart Association (NYHA) Class 2 or higher, or poorly controlled cardiac arrhythmias.
* Laboratory test abnormalities meeting any of the following criteria:

  1. Absolute neutrophil count (ANC) \<1,500/mm³.
  2. Platelet count \<75,000/mm³.
  3. Total bilirubin \>1.5 times the upper limit of normal (ULN).
  4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2.5 times ULN.
  5. Serum creatinine \>1.5 times ULN.
* Diagnosis of any malignancy other than advanced colorectal cancer within the 5 years preceding the start of study treatment, except for carcinoma in situ of the cervix, cured basal cell carcinoma, or bladder epithelial tumors.
* Patients with colorectal cancer amenable to curative surgical resection (however, those who explicitly refuse surgery or are deemed unsuitable for surgery may be eligible).
* History of substance abuse, drug use, or alcohol dependence.
* Lack of legal capacity or limited civil capacity.
* Any other condition that, in the opinion of the Investigator, makes the patient unsuitable for study participation.

Where this trial is running

Shanghai

• Second Affiliated Hospital of Naval Medical University — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Yuansheng Zang

Conditions: Colorectal Cancer