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

NCT04000737 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: YIV-906-2018L1
• Study Type: interventional
• Target: 62
• Locations: 4 countries
• Sites: 24

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; Hepatitis B (+) Associated Advanced Hepatocellular Carcinoma; Child-Plough A Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  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.

  At baseline, then at the end of every two cycle (i.e. approximately every 8 weeks), until disease progression or discontinuation from study. Assessed up to 24 months.

Secondary Outcomes (12)

• Time to progression (TTP)

  At baseline, then at the end of every two cycle (i.e. approximately every 8 weeks), until disease progression or discontinuation from study. Assessed up to 24 months.

• Overall survival (OS)

  at randomization, then at the end of every two cycle (i.e. approximately every 8 weeks), until death from any cause. Assessed up to 24 months.

• Objective response rate (ORR) in each arm

  At baseline, then at the end of every two cycle (i.e. approximately every 8 weeks), until disease progression or discontinuation from study. Assessed up to 24 months.

• Disease control rate (DCR) in each arm

  At baseline, then at the end of every two cycle (i.e. approximately every 8 weeks), until disease progression or discontinuation from study. Assessed up to 24 months.

• The safety and tolerability of the combination of YIV-906 plus sorafenib as measured by the rate and severity of AEs

  Continuously throughout the study until 28 days after treatment discontinuation

Study Arms (2)

Sorafenib + YIV-906

EXPERIMENTAL

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

Drug: Sorafenib+YIV-906

Sorafenib + Placebo

ACTIVE COMPARATOR

Patients in the placebo arm will be given sorafenib with placebo

Drug: Sorafenib+placebo

Interventions

Sorafenib+YIV-906 DRUG

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.

Also known as: PHY906, KD018

Sorafenib + YIV-906

Sorafenib+placebo DRUG

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.

Sorafenib + Placebo

Eligibility Criteria

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

You may qualify if:

• Male or females ≥18 years old with ability to take oral drugs
• Diagnosis of advanced (locally advanced or metastatic) unresectable/inoperable HCC according to the American Association for the Study of Liver Diseases (AASLD) Guidelines (Heimbach et al. 2018) or diagnosis by tissue pathology
• Participants categorized to stage B or C based on Barcelona Clinic Liver Cancer (BCLC) staging system
• Life expectancy of at least 3 months
• Presence of chronic hepatitis B (HBsAg (+))
• Never received systemic antitumor therapy
• Patients must have at least one tumor lesion that meets both of the following criteria:
• "Measurable disease" according to RECIST1.1, i.e. at least one measurable lesion.
• Advanced unresectable HCC that have liver limited disease who have failed and are not candidates to local therapies; or patients with extrahepatic disease.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Cirrhotic status of current Child-Pugh class A. Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
• For patients with positive HBV-DNA and positive HBsAg, they must be treated with anti-HBV treatment (per local standard of care), as prophylaxis starting at least 1-2 weeks prior to receiving study drug and willing to continue treatment for the length of the study
• Patients with adequate organ reserve, such as laboratory parameters:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 60000 x 10\^6/L

You may not qualify if:

• Patient who has any of the following criteria will be excluded from the trial:
• Patients who ever have HCV infection
• Patients who have received systemic chemotherapies or immunotherapy or molecular target therapies or anticancer Chinese medicine Cinobufacini
• Patients who have received any local anti-cancer therapy within 4 weeks prior to Cycle 1 treatment
• Active bleeding (including gastrointestinal bleeding) during the last 4 weeks prior to Cycle 1 treatment
• Patients with a history of allergy to the known components of YIV-906
• Known history of human immunodeficiency virus (HIV) seropositivity
• Known central nervous system metastasis including brain metastasis and meningeal carcinomatosis
• Hepatocholangiocarcinoma, fibrolamellar cell carcinoma and mixed hepatocellular carcinoma
• Active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma-in-situ of the cervix) within the past 5 years
• Any severe and/or uncontrolled medical conditions including but not limiting:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to Cycle 1 treatment, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
• Previous transient ischemic attack (TIA), cerebral vascular accident (CVA), symptomatic peripheral vascular disease (PVD) within last 6 months of Cycle 1 treatment
• Congenital long QT syndrome
• Alcoholic patients

Sponsors & Collaborators

• Yiviva Inc.: lead

Study Sites (24)

Calvin Pan. MD Gastroenterology & Hepatology Clinic

Flushing, New York, 11355, United States

Location

Northwell Monter Cancer Institute

Lake Success, New York, 11042, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Beijing You'An Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

China-Japan Friendship Hospital

Beijing, Beijing Municipality, China

Location

Foshan Hospital of Traditional Chinese Medicine

Foshan, Guangdong, China

Location

Guangdong Provincial Hospital of Traditional Chinese Medicine

Guangzhou, Guangdong, China

Location

The First Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Location

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Location

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

LongHua Hospital Shanghai University of Traditional Chinese Medicine

Shanghai, Shanghai Municipality, China

Location

Shanghai Eastern Hepatobiliary Hospital

Shanghai, Shanghai Municipality, China

Location

Shanghai University of Traditional Chinese Medicine Shuguang Hospital

Shanghai, Shanghai Municipality, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

Cancer Research Center, Taipei Municipal Wanfang Hospital

Taipei, Taiwan

Location

Taipei Medical University -Shuang Ho Hospital, Ministry of Health and Welfare

Taipei, Taiwan

Location

Taipei Medical University Cancer Center

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan District, Taiwan

Location

Related Publications (12)

• Lam W, Ren Y, Guan F, Jiang Z, Cheng W, Xu CH, Liu SH, Cheng YC. Mechanism Based Quality Control (MBQC) of Herbal Products: A Case Study YIV-906 (PHY906). Front Pharmacol. 2018 Nov 19;9:1324. doi: 10.3389/fphar.2018.01324. eCollection 2018.

  PMID: 30510512 BACKGROUND

• Chu E. Wedding Rigorous Scientific Methodology and Ancient Herbal Wisdom to Benefit Cancer Patients: The Development of PHY906. Oncology (Williston Park). 2018 Feb 15;32(2):e20-e27.

  PMID: 29492950 BACKGROUND

• Lam W, Jiang Z, Guan F, Huang X, Hu R, Wang J, Bussom S, Liu SH, Zhao H, Yen Y, Cheng YC. PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci Rep. 2015 Mar 30;5:9384. doi: 10.1038/srep09384.

  PMID: 25819872 BACKGROUND

• Rockwell S, Grove TA, Liu Y, Cheng YC, Higgins SA, Booth CJ. Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy. Int J Radiat Biol. 2013 Jan;89(1):16-25. doi: 10.3109/09553002.2012.717733. Epub 2012 Sep 3.

  PMID: 22856538 BACKGROUND

• Liu SH, Cheng YC. Old formula, new Rx: the journey of PHY906 as cancer adjuvant therapy. J Ethnopharmacol. 2012 Apr 10;140(3):614-23. doi: 10.1016/j.jep.2012.01.047. Epub 2012 Feb 3.

  PMID: 22326673 BACKGROUND

• Wang E, Bussom S, Chen J, Quinn C, Bedognetti D, Lam W, Guan F, Jiang Z, Mark Y, Zhao Y, Stroncek DF, White J, Marincola FM, Cheng YC. Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment. BMC Med Genomics. 2011 May 11;4:38. doi: 10.1186/1755-8794-4-38.

  PMID: 21569348 BACKGROUND

• Lam W, Bussom S, Guan F, Jiang Z, Zhang W, Gullen EA, Liu SH, Cheng YC. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med. 2010 Aug 18;2(45):45ra59. doi: 10.1126/scitranslmed.3001270.

  PMID: 20720216 BACKGROUND

• Saif MW, Li J, Lamb L, Kaley K, Elligers K, Jiang Z, Bussom S, Liu SH, Cheng YC. First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol. 2014 Feb;73(2):373-80. doi: 10.1007/s00280-013-2359-7. Epub 2013 Dec 3.

  PMID: 24297682 RESULT

• Kummar S, Copur MS, Rose M, Wadler S, Stephenson J, O'Rourke M, Brenckman W, Tilton R, Liu SH, Jiang Z, Su T, Cheng YC, Chu E. A phase I study of the chinese herbal medicine PHY906 as a modulator of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2011 Jun;10(2):85-96. doi: 10.1016/j.clcc.2011.03.003. Epub 2011 Apr 22.

  PMID: 21859559 RESULT

• Saif MW, Lansigan F, Ruta S, Lamb L, Mezes M, Elligers K, Grant N, Jiang ZL, Liu SH, Cheng YC. Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies. Phytomedicine. 2010 Mar;17(3-4):161-9. doi: 10.1016/j.phymed.2009.12.016. Epub 2010 Jan 22.

  PMID: 20092990 RESULT

• Yen Y, So S, Rose M, Saif MW, Chu E, Liu SH, Foo A, Jiang Z, Su T, Cheng YC. Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma. Anticancer Res. 2009 Oct;29(10):4083-92.

  PMID: 19846955 RESULT

• Farrell MP, Kummar S. Phase I/IIA randomized study of PHY906, a novel herbal agent, as a modulator of chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2003 Feb;2(4):253-6. doi: 10.3816/CCC.2003.n.007. No abstract available.

  PMID: 12620148 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis B

Interventions

PHY 906

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis

Study Officials

• Yun Yen, MD/PhD

  Taipei Medical University

  STUDY CHAIR

• Ghassan Abou-Alfa, MD/MBA

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 27, 2019
• Study Start: January 10, 2020
• Primary Completion: March 22, 2024
• Study Completion: November 19, 2024
• Last Updated: April 13, 2025

Record last verified: 2025-04

Locations

CN (12); HK (1); TW (7); US (4)