Brandon Twyford

DocwireNews

A novel phase II study investigating the triplet blockade of IL-27, PD-(L)1, and VEGF pathways in unresectable, locally advanced, or metastatic hepatocellular carcinoma (uHCC) demonstrated encouraging antitumor activity and a manageable safety profile. Presented at the 2025 ASCO Gastrointestinal Cancers Symposium by Daneng Li, MD, of the City of Hope National Comprehensive Cancer Center, the study highlights the potential of the first-in-class IL-27–targeting antibody, casdozokitug (casdozo), combined with atezolizumab (atezo) and bevacizumab (bev), as a promising treatment strategy.
Study Design and Methods
This open-label phase II trial enrolled 30 patients with previously untreated uHCC who received intravenous casdozo (10 mg/kg), atezo (1200 mg), and bev (15 mg/kg) every three weeks. The primary endpoints were safety and tolerability, with secondary endpoints including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR). The study population was predominantly male (77%), Asian (67%), and included patients with viral etiology (53% with hepatitis B virus, 17% with hepatitis C virus), metastatic spread (67%), and macrovascular invasion (13%).
Key Results
With a median follow-up of 15 months, triplet therapy demonstrated notable efficacy in patients with unresectable hepatocellular carcinoma. The ORR was 38% based on Response Evaluation Criteria In Solid Tumors (RECIST1.1) and 43% based on modified RECIST (mRECIST), with 17% of patients achieving a complete response. The median PFS was 8.1 months according to RECIST1.1 and 8.4 months according to mRECIST. In addition, median OS reached 19.9 months, and the 12-month survival rate was an impressive 85%. The DOR was not reached according to both RECIST1.1 and mRECIST evaluations, indicating that responses were both meaningful and durable. These results underscore the potential of the therapy to provide significant clinical benefit in this patient population.
Safety Profile
The combination therapy was associated with adverse events consistent with known profiles of the individual agents. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 67% of patients, with hypertension (20%) being the only TRAE reported in more than 10% of participants. Treatment-emergent adverse events led to study drug discontinuation in 30% of patients, but no treatment-related deaths were reported.
Biomarker Insights
Archival tissue from responders revealed IL-27+ tumor-associated macrophages (TAMs) in both viral and nonviral HCC cases, suggesting a potential biomarker for therapeutic response. Further biomarker analyses are underway to correlate immune responses and IL-27 pathway activity with clinical outcomes.
Implications and Future Directions
The study reinforces the potential of triplet blockade with casdozo, atezo, and bev as an innovative approach for managing uHCC, especially given its manageable safety profile and promising efficacy in a challenging patient population. The findings support continued investigation into IL-27–targeting therapies, with plans for additional clinical studies combining casdozo with toripalimab.

Emily Menendez

ASPEN-06 Phase 2 Final Analysis Demonstrates Benefit of ALX148 Combination for Gastric Cancer

Gastric Cancer

Stephen V. Liu, MD

Cecilia Brown

Changing Paradigms: Dr. Liu Discusses Implications of MARIPOSA OS Data

EGFR+ NSCLC

Rob Dillard

FDA Approves the First and Only Monotherapy for Treatment-Resistant Depression

Depression

Latest News

Promising Results for Triplet Blockade Therapy in Unresectable Hepatocellular Carcinoma

Liver Cancer

The study reinforces the potential of triplet blockade with casdozo, atezo, and bev as a viable approach for managing uHCC.

About Us

Editorial Policy

Advertising

eNewsletters

Contribute

Contact Us

MashupMD

Blood Cancers Today

Cancer Nursing Today

GU Oncology Now

Urban Health Today

Bile Duct Cancer

Colorectal Cancer

Gastroesophageal Cancer

GEP-NETs

GIST

Pancreatic Cancer

GI Oncology Now

Anemia

Deep Vein Thrombosis

Essential Thrombocythemia

Hemophilia

Immune Thrombocytopenic Purpura

Myelodysplastic Syndromes

Myelofibrosis

Myeloproliferative Neoplasms

Polycythemia Vera

Pulmonary Embolism

Sickle Cell Disease

Thrombocytopenia

Thrombophilia

Thrombosis

Thrombotic Thrombocytopenic Purpura

Venous Thromboembolism

von Willebrand Disease

Heme Today

Acute Kidney Injury

ADPKD

Anemia and Kidney Disease

Chronic Kidney Disease

COVID-19 and Kidney Disease

Diabetes and Hypertension

End-Stage Renal Disease

Gout

Hyperkalemia

IgAN

Kidney Transplantation

Metabolic Acidosis

Nephrology Times

Mesothelioma

Non-Small Cell Lung Cancer

Small Cell Lung Cancer

Squamous Cell Lung Carcinoma

Lung Cancers Today

Atherosclerotic Disease

Atrial Fibrillation

Heart Failure

Hypertension

Interventional Cardiology

Lipid Management

Practice Tips With Dr. Lichaa

Preventive Cardiology

Stroke

Cardiology

Breast Cancer

Gynecologic Cancer

Head and Neck Cancer

Skin Cancer

Oncology

Sleep

Urology

Diabetes

Ophthalmology

— Demodex Blepharitis

Neurology

Rheumatology

Gastroenterology

Pulmonology

Infectious Diseases

— HIV

Health and Wellness

Lupus

Future of Medicine

Orthopedics

Pharmacology

Career News

More

Conferences

CardioNerds

The Sleep Source With Dr. Morse

The Oncology Brothers

Rheumatology Rounds With Dr. Maheswaranathan

Healthcare Unfiltered

The Fellow on Call

Partners

Hurricanes & Health Care

Career Center

Expert Interviews

Subscribe