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Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus lenvatinib (Len) and cadonilimab as conversion therapy for downstaging.

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks.

HAIC

lenvatinib (8mg, qd) plus cadonilimab (10mg/kg, q3w)

Lenvatinib plus cadonilimab

Ze-yang Ding, M.D.

Han Gao

This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and cadonilimab as conversion therapy for unresectable hepatocellular carcinoma.

Cadonilimab is the world's first PD-1/CTLA-4 bispecific antibody tumor immunotherapy new drug, a tetrameric PD-1/CTLA-4 bispecific antibody, which can only bind to TIL tetravalent co-expressing PD-1 and CTLA-4. This design not only retains the efficacy observed in the combination therapy of PD-1 plus CTLA-4 inhibitors, but also reduces the risk of activated T cells attacking healthy tissues, thereby alleviating the toxicity problem outside the tumor. On June 29, 2022, the National Medical Products Administration of China approved the new drug Cadonilimab for the treatment of recurrent or metastatic cervical cancer patients who have failed platinum-based chemotherapy. Currently, a phase II clinical study of lenvatinib combined with Cadonilimab systemic treatment for advanced hepatocellular carcinoma is underway, and preliminary results reveal that in 30 enrolled patients, the ORR was 44.4%, the DCR was 77.8%, the treatment-related adverse reaction rate was 83.3%, but the incidence of grade 3 or above adverse reactions was only 26.7%. The safety of this antibody in patients is generally good. This study intends to evaluate the safety and efficacy of HAIC combined with lenvatinib and cadonilimab as a conversion regimen in unresectable hepatocellular carcinoma.

Combined HAIC, Lenvatinib and Cadonilimab as Conversion Therapy for Unresectable Hepatocellular Carcinoma

A Phase 2, Open-label, Single Arm Study of Combined HAIC, Lenvatinib and Cadonilimab as Conversion Therapy for Unresectable Hepatocellular Carcinoma

Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.

Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease; Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.

ORR=CR+PR.

Overall survival (OS): measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.

measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

Time to progression (TTP): measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.

Time to intrahepatic tumor progression (TTITP): measured from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST 1.1. This does not include death from any cause.

Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0)

Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used.

Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST

Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause

The life quality of every subject is assessed every 3 months during follow up according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.

Spots Global Cancer Trial Database for lenvatinib plus cadonilimab