AK112 with other therapies for advanced liver cancer

A Phase Ib/II Study of AK112 in Combination Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)

This trial will test AK112 alone or with other cancer drugs to see if it is safe and helps people with advanced hepatocellular carcinoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 280 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: immunotherapy, Sintilimab, Bevacizumab
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT06530251 on ClinicalTrials.gov

What this trial studies

The study has a Phase Ib dose‑finding part and a Phase II comparative part. In Phase Ib, patients with advanced HCC (BCLC B or C) who have had up to two prior systemic treatments will receive AK112 alone or in combination to determine dose‑limiting toxicities, the maximum tolerated dose, and the recommended Phase II dose. In Phase II, primarily systemic‑therapy‑naive patients with unresectable BCLC C (or noncurable BCLC B) will receive AK112 regimens or comparator therapy (sintilimab plus a bevacizumab biosimilar) to test safety and efficacy. Investigational agents include AK112, cadonilimab, AK127, AK130, and sintilimab, and study visits occur at specialized cancer centers in Beijing and Jinan, China.

Who should consider this trial

Good fit: Adults with advanced hepatocellular carcinoma (BCLC B or C), ECOG performance status 0–1, and life expectancy of at least 3 months—Phase Ib permits up to two prior anti‑tumor lines while Phase II enrolls patients who have not received prior systemic therapy for HCC.

Not a fit: Patients with poor performance status (ECOG ≥2), very limited life expectancy, or those eligible for curative or local therapies are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, AK112 combinations could provide a new systemic option that improves tumor control and outcomes for people with advanced HCC.

How similar studies have performed: Similar PD‑1 plus anti‑VEGF combination approaches (for example, sintilimab plus bevacizumab biosimilar) have shown clinical benefit in advanced HCC, providing precedent for this strategy.

Eligibility criteria

Inclusion Criteria:

1. Be able and willing to provide written informed consent.
2. Have a life expectancy of at least 3 months.
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. HCC confirmed by histology/cytology or confirmed by the American Society for the Study of Hepatology (AASLD) clinical diagnostic criteria for hepatocellular carcinoma in patients with cirrhosis.
5. Phase Ib:

   1. Barcelona Clinical Liver Cancer (BCLC) stage B or C.
   2. Has failed standard treatment and has received no more than two lines of anti-tumor treatment in the past;

   Phase II:
   1. The BCLC staging is stage C, which is not suitable for curative and local treatment, or for stage B that cannot be cured after curative and/or local treatment.
   2. Subjects who have not received any systematic anti-tumor treatment for HCC in the past.
6. According to RECIST v1.1, there is at least one untreatable measurable lesion, or a measurable lesion with clear imaging progression after local treatment, suitable for repeated and accurate measurement.
7. Liver function grading Child Pugh Grade A.
8. Has adequate organ function.
9. All subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
10. Able to to comply with all requirements of study participation (including all study procedures).

Exclusion Criteria:

1. Components confirmed by histology/cytology, such as fibrous layer hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
2. Except for HCC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other malignant tumors that have been cured through local treatment are not excluded, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ. If diagnosed with liver cancer or other malignant tumors more than 5 years before administration, pathological or cytological diagnosis of recurrent and metastatic lesions is required.
3. Tumor volume\>50% liver volume; Portal vein cancer thrombus (Vp4), inferior vena cava cancer thrombus.
4. Tumors invade important organs and blood vessels around them, and researchers have determined that entering the study will cause a higher risk of bleeding.
5. There is central nervous system (CNS) metastasis, spinal cord compression, or meningeal metastasis.
6. There are pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage.
7. Previously received immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, and any other treatments targeting the immune mechanisms of tumors.
8. Received local treatment for the liver within 4 weeks prior to the first administration; Received palliative radiotherapy for non liver patients within 2 weeks prior to initial administration.
9. There is a history of non infectious pneumonia that requires systemic glucocorticoid treatment, or current lung diseases including but not limited to interstitial lung disease, pneumoconiosis, silicosis, drug-related pneumonia, and severely impaired lung function.
10. History of severe bleeding tendency or coagulation dysfunction.
11. Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia.
12. Any arterial or venous thromboembolism events, transient ischemic attacks, cerebrovascular accidents, hypertensive crises, or hypertensive encephalopathy occurred within 6 months prior to the first administration of medication.
13. Pregnant or lactating female subject.
14. Any prior or concurrent disease, treatment, or laboratory test abnormality that may confuse study results, affect subjects' full participation in the study, or may not be in their best interest to participate.

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)
• Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital) — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Wenting Li

Conditions Hepatocellular Carcinoma