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Sorafenib

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Patients in the study arm will be treated orally for 28-day courses with YIV-906 + sorafenib

Patients in the placebo arm will be given sorafenib with placebo

Patients will be given sorafenib (400 mg BID) daily for a 28-day course with YIV-906 (3 capsules, BID) 4 days on and 3 days off weekly in each course.

YIV-906+Sorafenib

Patients will be given sorafenib (400 mg BID) daily for a 28-day course with placebo (3 capsules, BID) 4 days on and 3 days off weekly in each course.

Placebo+Sorafenib

Shwu-huey Liu, PhD

Calvin Pan, MD

James Harding, MD

Ghassan Abou-Alfa, MD

Xiuhui Li, MD

Yuankai Shi, MD

Liqun Jia, MD

Kaiping Jing, MD

Kaiping Jiang, MD

Shunqin Long, MD

Jianyong Yang, MD

Ruilian Xu, MD

Jian Kong, MD

Xiaohua Hu, MD

Shanzhi Gu, MD

Yingjie Zhu, MD

Kui Wang, MD

Chenghai Liu, MD

Man-Fung Yuen, MD

Long-Bin Jeng, MD

Chia-Jui Yen, MD

Jacqueline Whang-Peng, MD

Tzu-Yi Chao, MD

Huey-En Tzeng, MD

Yee Chao, MD

Chia-Hsun Hsieh, MD

Yun Yen, MD/PhD

Ghassan Abou-Alfa, MD/MBA

The aim of this study is to compare the efficacy and safety of YIV-906 plus standard-of-care sorafenib versus those of sorafenib alone as a first-line systemic treatment for patients with Hepatitis B (+) associated advanced hepatocellular carcinoma.

YIV-906 (PHY906, KD018) is an immune system modulator. Clinical and preclinical research suggests that YIV-906 could act to enhance the body's immune response to fight cancer and increase the anti-tumor activity of sorafenib and protect and repair the gastrointestinal tract by reducing inflammation and promoting tissue regeneration.

Inspired by a 1,800-year-old traditional medicine still in use today, YIV-906 is a botanical drug candidate, composed of an extract of four herbs and administered in oral capsule form.

The CALM (Combination of YIV-906 and Sorafenib to treat Advanced Liver cancer in a Multi-center study) trial is a multi-regional, randomized, placebo-controlled study.

HCC patients with chronic HBV (+) (HBsAg(+)), and Child-Pugh A status will be randomized to either the study arm (YIV-906 plus sorafenib) or control arm (placebo plus sorafenib) at ratio of 2:1. Patients will be stratified according to metastatic status (extrahepatic/vascular invasion vs. none), and their ECOG performance status (0 vs. 1) at randomization.

* ARM I: Patients receive Placebo + Sorafenib
* ARM II: Patients receive YIV-906+ Sorafenib

Patients in the study arm will be treated orally each 28-day course with YIV-906 (600 mg (3 capsules) BID) + sorafenib (400 mg BID) according to the following schedule: sorafenib BID daily treatment for 28 days, and YIV-906 BID 4 days on and 3 days off weekly in each course.

All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 5.0 (CTCAE). The Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) will be used to establish disease response or progression.

The RECIST 1.1 and mRECIST will be used in a blinded independent central review (BICR) to determine the study endpoints.

Patients will be evaluated for PFS, TTP, OS, antitumor response every two cycles, and QoL and safety at the beginning of each cycle. Biomarkers are mandatory and will be studied prior to drug administration on day 1 of each cycle. TCM Syndrome Research is optional.

PK is only applicable in China study sites and limited to the first 15 male and 15 female patients. Patients will be randomized to either the study drug arm or the placebo arm (2:1 ratio). PK studied immediately prior to dose administration and at 1 hour, 2 hours, 4 hours, and 12 hours post-dose administration on Day 1 of Cycles 1.

YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC)

A Phase II Randomized Placebo-Controlled Study Investigating The Combination Of YIV-906 And Sorafenib (Nexavar®) In HBV (+) Patients With Advanced Hepatocellular Carcinoma

PFS is defined as the period elapsing between the date of date of randomization and the date of either disease progression or date of death, whichever is earlier.

TTP is defined as the period elapsing between the date of randomization and the date of disease progression.

OS is defined as the interval between time of randomization and the date of death from any cause.

The Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) will be used to establish disease response or progression

DCR will be defined as the proportion of patients achieving either partial response (PR) or complete response (CR) or stable disease (SD).

All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 5.0 (CTCAE).

Each of the domains in the HCC18 will be scored per the assessment's scoring algorithm and summarized using descriptive statistics at baseline

Each of the domains in the EORTC QLQ-C30 will be scored per the assessment' scoring algorithm and summarized using descriptive statistics at baseline

PK is optional and limited to the first 15 male and 15 female patients from China study sites. Patients will be randomized to either study drug arm or placebo arm (2:1 ratio).

PK is optional and limited to the first 15 male and 15 female patients from China study sites.

Spots Global Cancer Trial Database for hepatitis b (+) associated advanced hepatocellular carcinoma