YIV-906 / Yiviva, Sanofi - LARVOL DELTA

Interpreting metabolic profiling of YIV906 in vivo: A Synergistic strategy combining LC-HRMS-based molecular networking and metabolomics thought integration. (PubMed, J Chromatogr A) - "Finally, a total of 63 prototype components and 180 metabolites including flavonoid, organic acid, monoterpenoid, triterpenoid and alkaloid were successfully identified in rat plasma and tissues based on the established strategy, as well as revealed the tissue distribution characteristics of main components. In conclusion, this study demonstrated an effective and practical strategy that enables the in-depth metabolic profiling of complex biological samples."

Journal • Preclinical • Oncology

Final analysis of a randomized, double blind, phase II study of sorafenib with or without YIV-906 in patients with advanced HCC (ESMO-GI 2025) - P2 | "Despite early closure of this study due to shifting treatment landscapes, and running concurrently during pandemic lockdowns, the trial's recruitment satisfied its statistical power requirement, meriting further HCC studies of YIV-906."

Clinical • Metastases • P2 data • Hepatocellular Cancer • IL6 • TNFA

Yiviva Presents Phase 2b Results for YIV-906 in Combination with Sorafenib in Advanced Hepatocellular Carcinoma at ASCO and ESMO GI 2025 (GlobeNewswire) - P2b | N=62 | CALM (NCT04000737) | Sponsor: Yiviva Inc. | "The study demonstrated improvements in both efficacy and tolerability for patients treated with YIV-906 plus sorafenib versus sorafenib monotherapy. (i) Median Progression-Free Survival (mPFS): 4.1 months vs. 3.5 months in the intention-to-treat (ITT) analysis; (ii) Median Overall Survival (mOS): 14.3 months vs 7.5 months; (iii) Median Time to Tumor Progression (mTTP): 5.59 months vs. 2.33 months; (iv) Safety and Tolerability: Patients on the YIV-906 arm patients demonstrated greater duration of treatment exposure and continuation and were able to remain on treatment longer."

P2b data • Hepatocellular Cancer

International phase II randomized placebo-controlled study investigating the combination of YIV-906 plus sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma. (ASCO 2025) - P2 | "Multi-targeted tyrosine kinase inhibitors, SORA and Lenvatinib, are first-line systemic treatment options for advanced HCC pts, are limited by high rates of grade ≥ 3 treatment-related adverse events. In this limited cohort of patients with confirmed HBV (+) HCC diagnosis, our findings suggest that YIV-906 is effective for increasing SORA's therapeutic index and clinical activity, and supports further studies of YIV-906."

Clinical • Metastases • P2 data • Hepatitis B • Hepatocellular Cancer • Oncology • Solid Tumor

YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2 | N=62 | Completed | Sponsor: Yiviva Inc. | Recruiting ➔ Completed | N=125 ➔ 62 | Trial completion date: May 2024 ➔ Nov 2024

Enrollment change • Trial completion • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor

A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer. (PubMed, J Gastrointest Oncol) - "The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers."

Clinical • Journal • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Rectal Cancer • Solid Tumor

Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis. (PubMed, Integr Cancer Ther) - "Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice."

Journal • Retrospective data • Review • Oncology • Solid Tumor

YIV-906 could modulate nuclear factor of activated T-cells (NFAT) activity of T cells for immune checkpoint blockade therapy and CAR T-cell therapy (AACR 2022) - P2 | "Currently, a phase II international clinical trial for using YIV-906 plus sorafenib to target HBV positive hepatocellular carcinoma as first line therapy (NCT04000737) had been initialized. This is worthy of further investigation. (Supported by research fund from Yiviva, inc)"

CAR T-Cell Therapy • Checkpoint inhibition • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD19 • CD69 • IFNG • NFATC1 • PD-L1 • ZAP70

YIV-906 enhances nuclear factor of activated T-cells (NFAT) activity of T cells and promotes immune checkpoint blockade antibody action and CAR T-cell activity. (PubMed, Front Pharmacol) - "In conclusion, YIV-906 modulates adaptive immunity by activating T effector cells mainly through its action on SHP1/2. YIV-906 could also facilitate immune checkpoint blockade therapy or CAR-T cell therapy for cancer treatment."

CAR T-Cell Therapy • Checkpoint block • Checkpoint inhibition • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Infectious Disease • Inflammation • Liver Cancer • Solid Tumor • CD19 • CD69 • NFATC1 • PD-L1

Pilot trial of KD018 with neo-adjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer. (ASCO 2017) - P=N/A; "Patients received 3D-conformal pelvic RT to 45 Gy in 1.8 Gy fractions, followed by a 5.4 Gy tumor boost with capecitabine 825mg BID on days 1-5 of RT (weekly) and KD018 800mg PO BID on days 1-4 of RT (weekly). This is the first clinical study of KD018 with concomitant RT and demonstrates the safety and favorable toxicity profile of this regimen compared to historical controls. These preliminary results warrant further study of the efficacy of KD018 as an adjuvant to pelvic CRT or RT to reduce GI toxicity. See table."

Biosimilar • Colorectal Cancer

YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2 | N=125 | Recruiting | Sponsor: Yiviva Inc. | Trial completion date: May 2023 ➔ May 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Preclinical Immunotherapy Research Featured in Poster Presentation at AACR 2022 Annual Meeting Highlights YIV-906’s Immunomodulatory Mechanisms in Combination with Immune Checkpoint or CAR T Therapy (GlobeNewswire) - "Yiviva and Yale scientists will present new data from Yiviva’s oncology portfolio at the 2022 American Association for Cancer Research (AACR) Annual Meeting in New Orleans on April 8-13, 2022. A poster presentation and abstract will highlight preclinical mechanism of action studies at Yale School of Medicine showing the potential of YIV-906 to modulate both adaptive immunity and innate immunity and facilitate immune checkpoint blockade therapy or CAR T-cell therapy for the treatment of cancer."

Preclinical • Oncology

YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2; N=125; Recruiting; Sponsor: Yiviva Inc.; Trial completion date: Feb 2022 ➔ May 2023; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A phase II randomized placebo-controlled study investigating the combination of yiv-906 and sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma (HCC). (ASCO-GI 2020) - P2; "Background: First-line systemic treatment options for advanced HCC pts are limited to the multi-targeted tyrosine kinase inhibitors, SORA and lenvatinib. Clinical trial information: NCT04000737. Research Funding: Yiviva Inc"

Clinical • P2 data

YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment. (PubMed, Sci Rep) - "Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatocellular Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • IFNG • IL4 • PD-L1

A four-component combination derived from Huang-Qin Decoction significantly enhances anticancer activity of irinotecan. (PubMed, Chin J Nat Med) - "Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity."

Journal • Gastrointestinal Disorder • Oncology • TNFA

YIV906 (PHY906) enhanced the antitumor activity of immune checkpoint blockade therapy: Anti-PD1 against liver cancer (AACR 2018) - "...Recently, FDA has approved Nivolumab (anti-PD1) for the treatment of hepatocellular carcinoma (HCC) patients previously treated with sorafenib...Our clinical results suggest that YIV906 has potential to increase the therapeutic index of capecitabine or sorafenib for HCC patient by improving quality of life and prolonging life...Y.-C. C is a fellow of NFCR, USA."

Checkpoint inhibition • IO biomarker • PD(L)-1 Biomarker • Hepatocellular Cancer • Melanoma

Recent Advances in Systemic Therapies for Advanced Hepatocellular Carcinoma. (PubMed, Curr Hepatol Rep) - "The recently approved combination of atezolizumab and bevacizumab based on the IMbrave150 trial has shown the most potential with the highest overall survival of any systemic agent in HCC to date, surpassing sorafenib. Despite COVID-19 delays, other promising trials that involve combining VEGF-directed therapy and checkpoint inhibition, cancer vaccines, phosphatidylserine, YIV-906, and oncolytic and immunotherapeutic vaccinia virus are actively recruiting patients...Given the promising data from the IMbrave150 trial, the combination of atezolizumab and bevacizumab is now the new first-line therapy. We discuss the change in landscape, the new second- and third-line systemic treatments in aHCC, and the ongoing clinical trials for newer agents including combination therapies."

Journal • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Infectious Disease • Novel Coronavirus Disease • Oncology • Solid Tumor

Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: City of Hope Medical Center; Active, not recruiting ➔ Completed; Trial completion date: Jan 2020 ➔ May 2020; Trial primary completion date: Jan 2020 ➔ May 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma. (PubMed, Oncologist) - "Our data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC."

Clinical • Combination therapy • Journal • P2 data • Fatigue • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Pain • Solid Tumor • AFP

Pilot Trial of KD018 With Neo-Adjuvant Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Rectal Cancer (clinicaltrials.gov) - P1; N=29; Completed; Sponsor: Yale University; Phase classification: P=N/A ➔ P1

Clinical • Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

WGCNA reveals key gene modules regulated by the combined treatment of colon cancer with PHY906 and CPT11. (PubMed, Biosci Rep) - "In conclusion, a total of 18 key genes were identified in this study. These genes showed strong correlation with PHY906-CPT11 treatment in colon cancer, which may help elucidate the underlying molecular mechanism of PHY906-CPT11 treatment in colon cancer."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ANXA2 • DDX5 • EIF4E • TMSB4X

Cancer Biomarkers for Integrative Oncology. (PubMed, Curr Oncol Rep) - "Studies on promising anti-cancer natural products, such as PHY906, honokiol, bryostatin-1, and sulforaphane have demonstrated the existence of potential cancer biomarker(s). A systematic approach is needed to identify and develop CAM treatment associated biomarkers and to define their role in facilitating clinical decision-making. The expectation is to use these biomarkers in determining potential options for CAM treatment, examining treatment effects and toxicity and/or clinical efficacy in patients with cancer."

Biomarker • Journal • Review • Oncology

YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2; N=125; Recruiting; Sponsor: Yiviva Inc.; Trial completion date: Jun 2021 ➔ Feb 2022; Trial primary completion date: May 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Mechanism based quality control (MBQC) for the four-herb Chinese medicine formulation, PHY906(YIV-906) and other herbal products (AACR 2017) - "Similarity index is only useful when relevant information is used. Mechanism based quality control could be used for other herbal products"

HEOR • Biosimilar • Oncology