GZ17-6.02 / Ionics Life Sci - LARVOL DELTA

GZ17-6.02 interacts with carboplatin and etoposide to kill neuroblastoma cells. (PubMed, Anticancer Drugs) - "Combined knockdown of Beclin1 and the death receptor CD95 almost abolished the antitumor actions of 602 and 602NR. 602, and more so 602NR, kills MYCN NB cells and interacts with standard-of-care chemotherapeutics to cause further killing via autophagy and death receptor signaling."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • BECN1 • EGFR • ERBB3 • ERBB4 • FAS • HER-2 • MYCN • ULK1

GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Virginia Commonwealth University | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Virginia Commonwealth University | Initiation date: Dec 2024 ➔ Mar 2025

Trial initiation date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A review on Arum palaestinum: phytochemical and biological aspects. (PubMed, Nat Prod Res) - "Extracts from its flowers demonstrated potent anti-inflammatory and dose-dependent cytotoxic effects. The potential of GZ17-6.02, a promising combinatorial drug made from plant components, for clinical cancer treatment is still being investigated."

Journal • Review • Oncology

GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Virginia Commonwealth University

New P1 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

GZ17-6.02 kills PDX isolates of uveal melanoma. (PubMed, Oncotarget) - P1 | "GZ17-6.02 interacted with doxorubicin or ERBB family inhibitors to significantly enhance tumor cell killing which was associated with greater levels of autophagosome formation and autophagic flux...The components of GZ17-6.02 were detected in tumors using a syngeneic tumor model. Our data support future testing GZ17-6.02 in uveal melanoma as a single agent, in combination with ERBB family inhibitors, in combination with cytotoxic drugs, or with an anti-PD1 immunotherapy."

IO biomarker • Journal • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • AMPK • ATG5 • BAP1 • BECN1 • FADD • FAS • PD-L1 • STAT3

GZ17-6.02 interacts with proteasome inhibitors to kill multiple myeloma cells. (PubMed, Oncotarget) - P1 | "The drug combination of GZ17-6.02 and bortezomib activated ATM, the AMPK and PERK and inactivated ULK1, mTORC1, eIF2α, NFκB and the Hippo pathway. HDAC knock down also enhanced ATG13 phosphorylation, increased BAK levels and reduced those of BCL-XL. Collectively, our present studies support performing additional in vivo studies with multiple myeloma cells."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • AMPK • ATG5 • BCL2L1 • BECN1 • MCL1

GZ17-6.02 interacts with bexarotene to kill mycosis fungoides cells. (PubMed, Oncotarget) - P1 | "Inhibition of autophagy and knock down of death-mediators downstream of the mitochondrion, AIF and caspase 3, almost abolished tumor cell killing. Hence in MF cells, GZ17-6.02 is a multi-factorial killer, utilizing ER stress, macroautophagy, death receptor signaling and directly causing mitochondrial dysfunction."

Journal • Cutaneous T-cell Lymphoma • Dermatology • Metabolic Disorders • Mycosis Fungoides • Oncology • Solid Tumor • AMPK • BCL2L1 • BECN1 • CASP3 • FAS • MCL1

Transcriptomic and proteomic analysis of tumor suppressive effects of GZ17-6.02 against mycosis fungoides. (PubMed, Sci Rep) - "In a subcutaneous tumor model, GZ17-6.02 decreased tumor volume (p = .002) and weight (p = .009) compared to control conditions. Proteomic analysis of tumor samples showed that GZ17-6.02 suppressed the expression of several proteins that may promote CTCL growth, including mitogen-activated protein kinase (MAPK)1, MAPK3, Growth factor receptor bound protein (GRB)2, and Mediator of RAP80 interactions and targeting subunit of 40 kDa (MERIT)40."

Journal • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • T Cell Non-Hodgkin Lymphoma • MAPK1 • MAPK3 • TNFA

Topical GZ21T Inhibits the Growth of Actinic Keratoses in a UVB-Induced Model of Skin Carcinogenesis. (PubMed, JID Innov) - "We recently showed that GZ17-6.02, an anticancer agent composed of curcumin, haramine, and isovanillin, inhibited the growth of H297.T cells...RNA sequencing and proteomic analyses revealed that GZ21T suppressed several pathways, including MAPK (P = 0.025), phosphoinositide 3-kinase-protein kinase B (P = 0.04), HIF-1α (P = 0.016), Wnt (P = 0.025), insulin (P = 0.018), and ERBB (P = 0.016) signaling. GZ21T also upregulated the autophagy-promoting protein AMPK while suppressing proteins such as PD-L1, glutaminase, pAkt1 S473, and eEF2K."

Journal • Actinic Keratosis • Dermatology • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • AMPK • EEF2K • HIF1A • PD-L1

A novel combination of isovanillin, curcumin, and harmine (GZ17-6.02) enhances cell death and alters signaling in actinic keratoses cells when compared to individual components and two-component combinations. (PubMed, Anticancer Drugs) - "Blockade of both autophagy and death receptor signaling abolished drug-induced actinic keratosis cell death. Our data demonstrate that the unique combination of isovanillin, curcumin, and harmine represents a novel therapeutic with the potential to treat actinic keratosis in a manner different from the individual components or pairs of the components."

Journal • Actinic Keratosis • Dermatology • Oncology • Skin Cancer • ATG5 • BECN1

GEN-602-CT-101: Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer (clinicaltrials.gov) - P1 | N=127 | Active, not recruiting | Sponsor: Genzada Pharmaceuticals USA, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Monotherapy • Basal Cell Carcinoma • Breast Cancer • Colorectal Cancer • Cutaneous T-cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • T Cell Non-Hodgkin Lymphoma • ER • HER-2 • PGR

GZ17-6.02 kills prostate cancer cells in vitro and in vivo. (PubMed, Front Oncol) - "GZ17-6.02 interacted with olaparib to further suppress the growth of LNCaP tumors without ultimately enhancing animal survival. Our data support the consideration of GZ17-6.02 as a possible therapeutic agent in patients with AR+ prostate cancer."

Journal • Preclinical • Ataxia • Genito-urinary Cancer • Hematological Malignancies • Immunology • Lymphoma • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • AMPK • AR • ATG5 • BECN1 • PTEN

[VIRTUAL] Phase I study of oral GZ17-6.02 in patients with advanced solid tumors or lymphoma (ESMO 2021) - P1 | "GZ17-6.02 was biologically active and demonstrated an acceptable and manageable safety profile in a heavily pretreated patient population with various malignancies. This phase 1 data provides rational for further investigation in a phase 2 setting to determine GZ17-6.02’s safety and potential efficacy in defined patient populations, both as monotherapy and in combination with other therapeutics."

Clinical • P1 data • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

GZ17-6.02 Inhibits the Growth of EGFRvIII+ Glioblastoma. (PubMed, Int J Mol Sci) - "Finally, a subcutaneous xenograft model showed that GZ17-6.02 inhibits glioblastoma growth in vivo. We conclude that GZ17-6.02 is a promising combination drug effective at inhibiting the growth of a subset of glioblastomas and our data warrants further preclinical studies utilizing xenograft models to identify patients that may respond to this drug."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR

GEN-602-CT-101: Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer (clinicaltrials.gov) - P1 | N=127 | Recruiting | Sponsor: Genzada Pharmaceuticals USA, Inc. | N=44 ➔ 127 | Trial completion date: Dec 2021 ➔ Dec 2023 | Trial primary completion date: May 2021 ➔ May 2023

Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Breast Cancer • Colorectal Cancer • Cutaneous T-cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • T Cell Non-Hodgkin Lymphoma • ER • HER-2 • PGR

Genzada Pharmaceuticals Opens Phase 1B Metastatic Breast Cancer Trial (AP News) - "Genzada Pharmaceuticals USA Inc. (Genzada), a subsidiary of Ionics Pharmaceuticals SA, announced today the official opening of a Phase 1B clinical trial for the oral therapeutic GZ17-6.02 (6.02) in combination with capecitabine in patients with metastatic breast cancer....The first site to open is Texas Oncology in Dallas, Texas, headed by leading breast cancer expert Dr. Joyce O’Shaughnessy."

New P1 trial • Breast Cancer • Oncology • Solid Tumor

Mechanisms of GZ17-6.02 resistance. (PubMed, Anticancer Drugs) - P1 | "Our findings demonstrate that GZ17-6.02 has the potential to be developed as a colon cancer therapeutic and that resistance to the drug can be partially reversed by HDAC inhibitors."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • FAS • HER-2 • PDGFRB • STAT5

GZ17-6.02 and axitinib interact to kill renal carcinoma cells. (PubMed, Oncotarget) - "We conclude that GZ17-6.02 and axitinib interact to kill requiring ER stress signaling, autophagy and death receptor signaling. Autophagic degradation of HDACs played a key role in enhancing MHCA expression and of a potential improved response to checkpoint inhibitory immunotherapy."

IO biomarker • Journal • Genito-urinary Cancer • Hematological Malignancies • Kidney Cancer • Lymphoma • Oncology • Renal Cell Carcinoma • Solid Tumor • AMPK • ATG5 • BAK1 • BCL2L1 • BECN1 • FADD • FAS • HER-2 • KIT • MCL1 • MET • STAT3 • STAT5

GZ17-6.02 and palbociclib interact to kill ER+ breast cancer cells. (PubMed, Oncotarget) - "The drugs also increased the phosphorylation of the AMPK and ATG13, effects blocked by knock down of ATM. Knock down of ATM or the AMPK, or expression of activated mTOR significantly reduced the abilities of GZ17-6.02 and palbociclib to enhance autophagosome formation and autophagic flux."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lymphoma • Oncology • Solid Tumor • AMPK • ATG5 • BAX • BCL2L1 • BECN1 • ER • ERBB3 • FAS • MCL1

[VIRTUAL] GZ17-6.02 induces apoptosis and modulates mTOR/PI3K/AKT and autophagy signaling in mycosis fungoides (EADV 2021) - No abstract available

Cutaneous T-cell Lymphoma • Dermatology • Mycosis Fungoides • Oncology

GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins. (PubMed, Front Oncol) - "Erlotinib, afatinib, and osimertinib interacted with GZ17-6.02 to kill NSCLC cells expressing mutant EGFR proteins. The drug combination reduced the expression of HDAC2 and HDAC3, which correlated with lower PD-L1, IDO1, and ODC levels and increased MHCA expression. Collectively, our data support consideration of combining GZ17-6.02 and pemetrexed in osimertinib-resistant NSCLC."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AMPK • ATG5 • BCL2L1 • BECN1 • CASP9 • EGFR • HDAC2 • IDO1 • MAP2K1 • PD-L1

GZ17-6.02 Interacts With [MEK1/2 and B-RAF Inhibitors] to Kill Melanoma Cells. (PubMed, Front Oncol) - "Regardless of vemurafenib resistance, the drugs alone or in combination all reduced the expression of PD-L1 and increased the levels of MHCA, which was linked to degradation of multiple HDAC proteins. Our findings support the use of GZ17-6.02 in combination with trametinib/dabrafenib in the treatment of melanomas expressing mutant B-RAF V600E proteins."

IO biomarker • Journal • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • AMPK • ATG5 • BRAF • FADD • FAS • MAP2K1 • PD-L1 • STAT3 • STAT5

[VIRTUAL] A novel plant-derived compound induces apoptosis and cell death in mycosis fungoides (SID 2021) - P1 | "GZ17-6.02 (6.02) is a novel investigational agent composed of three plant-derived compounds: curcumin, harmine, and isovanillin. In a subcutaneous HH tumor mouse model, mean (SD) tumor volumes for 6.02-, bexarotene-, and vehicle-treated mice at 31 days of treatment were 1718 (650) mm3 , 1682 (419) mm3 , and 2335 (1096) mm3 in, respectively. These results suggest that 6.02 is effective in inhibiting tumor growth, similar to bexarotene treatment."

IO biomarker • Cutaneous T-cell Lymphoma • Dermatology • Mycosis Fungoides • Oncology • Solid Tumor • BCL2

Super-enhancers: Possible target in pancreatic cancer for therapeutic approaches (AACR 2018) - "There is no systematic study showing an association of SE with pancreatic cancer so far. Hence, in the present study, we have established that several super-enhancer marks can be targeted by combination of natural compounds, GZ17-6.02, in PDAC. This study concludes that super-enhancers can be an important therapeutic target for PDAC."

IO Biomarker • Pancreatic Cancer