AK104 Combining With TACE for Resectable Hepatocellular Carcinoma (MORNING)

NCT05578430 | Unknown Phase 2

• 1 other identifier: HCC2022
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 2, open-label, single-arm study of neoadjuvant immune-checkpoint blockade therapy (AK104) combining with TACE for resectable hepatocellular carcinoma. The purpose is to investigate the efficacy and safety of this therapeutic regimen to reduce the risk of postoperative recurrence in resectable HCC patients with a high risk of recurrence.

Conditions

Resectable Hepatocellular Carcinoma

Keywords

Resectable Hepatocellular Carcinoma; Neoadjuvant Treatment; Immune-checkpoint Blockade; TACE

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response Rate (MPR rate)

  MPR rate is defined as the percentage of patients with over 90% of histological tumor tissue necrosis removed after neoadjuvant TACE combined with AK104 treatment.

  Up to 2 years

Secondary Outcomes (3)

• 1-year recurrence rate

  The percentage of patients who suffer recurrence one year after surgery.

• Objective response rate (ORR)

  ORR is defined as the percentage of patients who have achieved complete response (CR) or partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, after neoadjuvant TACE combined with AK104 treatment but before

• Incidence of Adverse Events (AE)

  The percentage of patients who suffer grade 3 or worse adverse events from the first dose of administration to last follow-up, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Study Arms (1)

TACE+Cadonilimab+Surgery

EXPERIMENTAL

After appropriate screening and randomization, patients enrolled will receive TACE plus 2-cycle of Cadonilimab treatment before surgery. Four weeks later after surgery, Cadonilimab treatment will be followed up to 16 cycles.

Drug: Cadonilimab; Procedure: TACE; Procedure: Surgery

Interventions

Cadonilimab DRUG

10mg/kg by intravenous infusions every 3 weeks

Also known as: AK104

TACE+Cadonilimab+Surgery

TACE PROCEDURE

TACE will be performed per institutional standard of care.

TACE+Cadonilimab+Surgery

Surgery PROCEDURE

Surgery will be performed per institutional standard of care.

TACE+Cadonilimab+Surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years but ≤75 years
• Resectable HCC staged BCLC A/B
• Treatment naïve for HCC
• High risk for recurrence, meeting at least one of the following criteria:
• Multiple tumor lesions
• Individual tumor \> 5cm
• AFP \> 400 ug/L
• MVI positive based on preoperative MRI according to MVI predictive model of Radiomics
• Measurable or evaluable lesions according to RECIST v1.1 criteria
• ECOG performance status 0-1
• Child-Pugh class A
• Life expectancy ≥ 12 weeks
• Adequate organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥ 1,500/μL

You may not qualify if:

• Any prior treatment for HCC.
• Tumor rupture or bleeding. Suspected abdominal metastasis.
• A major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to enrollment.
• History of allogenic organ transplantation.
• Under other clinical trials.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion: vitiligo or alopecia, hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement, any chronic skin condition that does not require systemic therapy or celiac disease controlled by diet alone.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AK104 or other immune checkpoint inhibitors.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (including tuberculosis), uncontrolled hypertension (defined as blood pressure of \> 140/90 mmHg during the screening period despite medical management), interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
• History of hepatic encephalopathy, refractory ascites or esophagogastric varices with high risk of bleeding. Upper gastrointestinal hemorrhage within the year prior to the first dose of study drug.
• Active hepatitis B infection without treatment (positive HBV surface antigen (HBsAg) and HBV DNA ≥ 1000 IU/ml). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Active hepatitis C infection (positive HCV antibody and HCV RNA above the lower limit of detection).
• A primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of a stroke within the year prior to the first dose of study drug.
• History of active primary immunodeficiency.
• History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study agent. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection). Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or its equivalent. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug. Note: Patients, if enrolled, should not receive live vaccine whilst receiving study drug and for at least 30 days after the last dose of study agent.

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Interventions

Surgical Procedures, Operative

Central Study Contacts

Kuang Ming, Ph.D.

CONTACT

008687755766; kuangm@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 13, 2022
• Study Start: January 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: December 15, 2022

Record last verified: 2022-12