Phase I, Open-label, Dose Escalation Study to Assess Safety and Tolerability of SOR-C13 in Subjects With Advanced Solid Tumors Commonly Known to Express the TRPV6 Ion Channel

The purpose of this study is to determine the safety and tolerability of the drug SOR-C13 when given as an intravenous infusion in patients with ovarian cancer or other cancers known to over express the TRPV6 calcium channel.

开始日期2012-07-01

申办/合作机构

Soricimed Biopharma, Inc.

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项与 Soricimed Biopharma, Inc. 相关的文献（医药）

2018-07-01·Cancer Research

Abstract 2891: Molecular profiling of hormone-resistant prostate cancer cells with TRPV6 oncochannel knockout/knockdown

作者: MacCormack, Tyson ; Stewart, John M. ; Davey, Michelle ; Lutes, Tyler ; Dugourd, Dominique ; Rice, Christopher

AbstractTRPV6 calcium channel is a recognized oncochannel over-expressed in a number of epithelial cancers (e.g. breast, ovarian, prostate). TRPV6, a member of one of seven subfamilies of TRP channels, plays an important role in Ca2+ absorption from the intestinal lumen. TRPV6 over-expression is associated with a poor prognosis particularly with breast and prostate cancers. Although some TRPV6 mechanistic work is available and indicates that NFAT is involved, there is a need to better understand pathways involved in its mechanism of action (MOA). These data could allow the identification of clinically relevant biomarkers and identify potential for synergy of TRPV6-targeting therapies with other anti-cancer treatments. To determine which key pathways TRPV6 influences in prostate cancer, two TRPV6 knockouts (KO) were produced in a castration-resistant prostate cancer cell line (PC-3) using the CRISPR-Cas9 approach with two different gRNAs. In addition, knockdowns (KD) were produced by transfecting PC-3 cells with two TRPV6 siRNA targeting different regions of TRPV6 mRNA. The mRNA expression of 184 genes was analyzed using an RT-qPCR TaqMan array. The panel consisted of genes involved in cancer calcium signalling, genes that have been associated with the MOA of TRPV6 and genes directly or indirectly involved in NFAT signalling. Gene profiling results were generally consistent between the TRPV6 KD and KO cells. Results showed a dramatic reduction in expression of TRPV6 mRNA in the KO/KD cells (14 to 166-fold). TRPV6 KO/KD affected multiple genes involved in cancer cell proliferation (e.g. ESR1, CDH1), metastasis (e.g. SNAI1, MUC1/16), resistance to apoptosis (e.g. Bcl-2-type proteins, Fos) and angiogenesis (e.g. VEGFA/B, FLT4), as well as genes involved in the M2 immune tumor microenvironment (e.g. IL6 and VEGFA). The TRPV6 KO/KD data confirm the basic MOA of TRPV6, activating NFAT by increasing cytosolic calcium and provide information on the downstream pathways involved (e.g. NF-kB, estrogen and MAPK). The data allow for the identification of clinical efficacy biomarkers for TRPV6 inhibitors (e.g. a panel of CXCL12, FLT4, MUC16 and IL-6). Furthermore, results indicate TRPV6 inhibitors have the potential to modify the immune composition of the tumor microenvironment from a tumor promoting to a tumor control response, and thus may help trigger an anti-cancer immune defence. This study demonstrates a central role of TRPV6 and calcium signalling in cancer development.Citation Format: Tyler Lutes, Michelle Davey, Christopher Rice, Tyson MacCormack, John M. Stewart, Dominique Dugourd. Molecular profiling of hormone-resistant prostate cancer cells with TRPV6 oncochannel knockout/knockdown [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2891.

2018-07-01·Cancer Research

Abstract 1936: The central role of NFAT signalling in the mechanism of action of the TRPV6 oncochannel inhibitor and clinical candidate SOR-C13

作者: Stewart, John M. ; MacCormack, Tyson J. ; Dugourd, Dominique ; Rice, Christopher ; Lloyd, Vett ; Lutes, Tyler ; Davey, Michelle

AbstractSOR-C13, a 13-mer peptide derived from soricidin, the paralytic peptide in saliva of the Northern Short-tailed shrew, has completed an open-label, all comers Phase I Clinical Trial for the treatment of epithelially-derived cancers. SOR-C13 is a first-in-class drug candidate for the treatment of solid tumors. SOR-C13 specifically targets and inhibits the TRPV6 calcium channel - a recognized oncochannel whose over-expression in a number of epithelial cancers (e.g. breast, ovarian, prostate) is associated with poor prognosis. An increase in TRPV6 facilitates calcium influx into the cell, which activates the calcium binding protein calmodulin. This complex in turn activates calcineurin that de-phosphorylates and activates Nuclear Factor of Activated T-cells (NFAT), a gene transcription factor involved in multiple oncogenic processes. To demonstrate the role of NFAT activation in the mechanism of action (MOA) of SOR-C13, breast cancer cells (T-47D) were transfected with a NFAT dual reporter plasmid, treated with the peptide, and NFAT activation monitored. Additionally, RT-qPCR TaqMan array profiling was performed on prostate (PC-3), breast (T-47D), ovarian (OVCAR-3 and SK-OV-3), and pancreatic (BxPC-3 and SU.86.86) cancer cell lines treated with SOR-C13 compared with untreated cells. The TaqMan array panel consisted of 187 genes involved in cancer calcium signalling associated with the MOA of TRPV6 and directly, or indirectly, involved in NFAT signalling. SOR-C13 treatment significantly inhibited NFAT activation (p < 0.05) in T-47D cells transfected with a NFAT reporter plasmid. Molecular profiling of the 6 cancer cell lines showed that many genes involved in NFAT signalling were modulated by SOR-C13 treatment. Affected genes included genes involved in cell proliferation (e.g. TGF-beta, TLR9), metastasis (e.g. ADAM12, CEACAM6), resistance to apoptosis (e.g. WISP1) and angiogenesis (e.g. FLT4). Cytokines (e.g. IL-6) and chemokines (e.g. CXCL12), involved in cancer progression and associated with NFAT signalling, as well as transcription factors (e.g. GATA4, NF-kB) were down regulated upon SOR-C13 treatment. These results highlight NFAT signalling in the mechanism of action of SOR-C13. The impact of SOR-C13 on the expression of genes involved in resistance to apoptosis, proliferation, metastasis and angiogenesis as well as on the expression of immune cytokines and transcription factors in multiple cancer cells, makes SOR-C13 an attractive, novel anti-cancer drug.Citation Format: Christopher Rice, Tyler Lutes, Michelle Davey, Vett Lloyd, Tyson J. MacCormack, John M. Stewart, Dominique Dugourd. The central role of NFAT signalling in the mechanism of action of the TRPV6 oncochannel inhibitor and clinical candidate SOR-C13 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1936.

2017-06-01·Investigational New Drugs3区 · 医学

First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors

3区 · 医学

Article

作者: Ilenchuk, T T ; Dugourd, D ; Fu, S ; Lutes, T ; Welch, S ; Rice, C ; Liu, L ; Hong, D ; Stewart, J M ; Gong, J ; Fields, N ; Nemet, A ; Hirte, H ; Subbiah, V ; Piha-Paul, S

SummaryIntroduction This was an open-label, dose escalation (3 + 3 design), Phase I study of SOR-C13 in patients with advanced tumors of epithelial origin. Primary objectives were to assess safety/tolerability and pharmacokinetics. Secondary goals were to assess pharmacodynamics and efficacy of SOR-C13. Methods SOR-C13 was administered IV QD on days 1–3 and 8–10 of a 21-day cycle. Doses were 2.75 and 5.5 mg/kg (20-min infusion) and 1.375, 2.75, 4.13 and 6.2 mg/kg (90-min infusion). Toxicity was assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose limiting toxicity (DLT) was assessed within the first treatment cycle. Tumors were evaluated, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, after two cycles. Results Twenty-three patients were treated. No drug-related serious adverse events occurred. DLTs occurred in six patients: asymptomatic, drug-related, transient Grade 2 hypocalcemia (4 patients), and unrelated Grade 3 anemia and Grade 3 atrial fibrillation, 1 patient each. Calcium and vitamin D supplementation eliminated further Grade 2 hypocalcemia. One Grade 3 treatment emergent adverse event, urticaria, was definitely related to SOR-C13. Four possibly drug-related, Grade 3 events (alanine aminotransferase and aspartate aminotransferase elevation, headache, and hypokalemia) were observed. Of 22 evaluable patients, 54.5% showed stable disease ranging from 2.8 to 12.5 months. The best response was a 27% reduction in a pancreatic tumor with a 55% reduction in CA19–9 levels at 6.2 mg/kg. Conclusion SOR-C13 was safe and tolerated up to 6.2 mg/kg. The Maximal Tolerated Dose (MTD) was not established. Stable disease suggested antitumor activity.

项与 Soricimed Biopharma, Inc. 相关的新闻（医药）

2022-12-13

·BioSpace

Soricimed Appoints Leading North American Cancer Researcher Dr. Siqing Fu to its Scientific Advisory Board

MONCTON, NB, Dec. 13, 2022 /CNW/ - Soricimed Biopharma Inc., ("Soricimed" or "the Company"), a clinical stage company focused on the development and commercialization of first-in-class targeted cancer therapeutics, has appointed Dr. Siqing Fu, a North American leader in cancer research, to its Scientific Advisory Board. "We are honoured to have Dr. Fu join our Scientific Advisory Board at this pivotal time for our company," said Robert Bruce, Chief Executive Officer of Soricimed. "He brings extensive experience to the research table including investigational cancer therapies – specifically in novel design for phase I and II clinical trials. Dr. Fu's expertise will help enhance the trajectory of our work as we look to continue to validate the efficacy of our targeting platform in treating solid tumour cancers." "I am pleased to be joining Soricimed as a scientific advisor," said Dr. Fu. "Their platform, and the emergence of TRPV6 as a target in the treatment of cancer, have significant potential in multiple oncology applications. The results to date for Soricimed's targeting platform are promising and show that it could be a game-changing frontline therapy for this difficult disease." Dr. Fu has over 20 years of experience in cancer research and is currently a professor in the Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center. His research interests include novel design for Phase I/II clinical trials and chemosensitization via biological targeting agents like epigenetic therapy as complementary medicine for cancer treatment. He received his MD from Tongji Medical University (Shanghai, China) and a Clinical Fellowship, Section of Hematology and Medical Oncology, from the University of Rochester in New York, United States. About Soricimed Biopharma Inc. Soricimed is a privately held clinical stage company focused primarily on the development of targeted, first-in-class cancer treatments. Soricimed was established following the discovery of a unique and proprietary family of paralytic and anti-cancer peptides. The Company is committed to translating this discovery into novel therapies that deliver powerful treatment options for those living with devastating conditions. Soricimed's clinical stage oncology drug candidate, SOR-C13, a targeted anti-cancer peptide, has been granted orphan drug status for the treatment of pancreatic and ovarian cancers by the U.S. Food and Drug Administration. In addition, a portfolio of targeted Peptide-drug Conjugates (PDCs) and Peptide Receptor Radionuclide Therapies (PRRTs) are in various stages of pre-clinical development. For more information, visit . For more information about Soricimed and/or this announcement, please contact: Media Relations: Nick Williams NATIONAL Public Relations nwilliams@national.ca 647-354-2478 Investor Relations: Stephen Kilmer President, Kilmer Lucas Inc. stephen@kilmerlucas.com 646-274-3580 SOURCE Soricimed Biopharma

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药物(靶点)	适应症	全球最高研发状态

SBI-PDC01 ( TRPV6 )	前列腺癌更多	临床前
SBI-1301 ( TRPV6 )	肿瘤更多	临床前
212Pb peptide receptor radionuclide therapy (Orano Med) ( TRPV6 )	实体瘤更多	药物发现
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