AK112 plus chemotherapy versus bevacizumab plus chemotherapy for first-line metastatic colorectal cancer

A Randomized, Controlled, Multicenter Phase III Clinical Study of AK112 Combined With Chemotherapy Versus Bevacizumab Combined With Chemotherapy in First-line Metastatic Colorectal Cancer

This tests whether adding AK112 to standard chemotherapy works better than bevacizumab plus chemotherapy as the first treatment for people with metastatic colorectal cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 560 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: bevacizumab, chemotherapy
• Locations: 2 sites (Guanzhou, Guangdong and 1 other locations)
• Trial ID: NCT06951503 on ClinicalTrials.gov

What this trial studies

This is a Phase III, randomized comparison of AK112 combined with standard chemotherapy regimens versus bevacizumab combined with the same chemotherapy in adults with previously untreated metastatic colorectal adenocarcinoma. Eligible participants must have measurable disease by RECIST v1.1, ECOG 0-1, be aged 18–75, and have had no prior systemic therapy in the metastatic setting (prior adjuvant therapy allowed if relapse occurred ≥12 months after last dose). Treatments include AK112 or bevacizumab given alongside oxaliplatin- or irinotecan-based regimens with leucovorin and 5-FU, with planned follow-up for safety and tumor response. The trial will monitor efficacy and adverse events to determine whether AK112 offers better outcomes than the current bevacizumab-containing standard.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed metastatic colorectal adenocarcinoma, measurable disease, ECOG 0–1, adequate organ function, and no prior systemic therapy for metastatic disease (prior adjuvant therapy allowed if relapse ≥12 months).

Not a fit: Patients who are candidates for curative local therapy, have poor performance status, recent adjuvant relapse (<12 months), or significant organ dysfunction are unlikely to qualify or benefit from this comparison.

Why it matters

Potential benefit: If successful, AK112 plus chemotherapy could improve tumor control and survival compared with current bevacizumab-containing first-line regimens.

How similar studies have performed: Bevacizumab plus chemotherapy is an established first-line option, while AK112 is a newer agent with limited earlier-phase data, so similar combination approaches have shown promise but are not yet proven in large randomized settings.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent.
2. Age ≥ 18 years and ≤ 75 years.
3. ECOG status of 0 or 1.
4. Estimated survival ≥ 3 months.
5. Subjects with histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
6. Subjects who are not candidates for radical surgical resection or local therapy and have not received systemic anti-tumor therapy in the recurrent or metastatic setting. Subjects who have received prior neoadjuvant or adjuvant therapy and whose first discovery of recurrence or metastases is ≥ 12 months after the last dose of neoadjuvant or adjuvant therapy are allowed to enroll.
7. At least one measurable disease based on RECIST v1.1.
8. Adequate organ function per protocol-defined criteria.
9. Women of childbearing potential and men with female partners of childbearing potential must agree to use effective contraception during treatment and for at least 180 days following the last dose of study treatment.

Exclusion Criteria:

1. Previous (within 3 years) or concurrent other malignant tumors, excluding those that have been cured.
2. Participating in other interventional study within 4 weeks prior to the first study drug administration.
3. Palliative local treatment for non-target lesions within 2 weeks prior to the first administration; received non-specific immunomodulatory therapy within 2 weeks prior to the first administration.
4. Current presence of uncontrolled combined disease.
5. Active clinical infections.
6. History of severe bleeding tendency or coagulation dysfunction.
7. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection.
8. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study.
9. Current presence of significant radiographic or clinical manifestations of GI obstruction.
10. Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0).
11. Pregnant or lactating women.
12. Any condition considered by the investigator to be inappropriate for enrollment.
13. Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival.

Where this trial is running

Guanzhou, Guangdong and 1 other locations

• The Sixth Hospital,Sun Yat-sen University — Guanzhou, Guangdong, China (Recruiting)
• Sun Yat-sen University Cancer Center — Guanzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Xufang Yu, MD

Conditions Colorectal Adenocarcinoma