Clinical Trials

Date: 2017-10-02

Type of information: Treatment of the first patient

phase: 1

Announcement: treatment of the first patient

Company: Pieris (Germany)

Product: PRS-343

Action mechanism:

• bispecific antibody/immunotherapy product. PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137).
• PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). CD137/4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes, and is therefore, an attractive target for cancer immunotherapy.
• Pieris' bispecifics are designed to promote CD137 clustering by bridging T cells with HER2-positive tumor cells, and to thereby provide a localized costimulatory signal to tumor antigen-specific T cells.
• PRS-343 is a bispecific monoclonal antibody-Anticalin fusion protein comprised of a HER2 tumor-targeting antibody genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based bispecific therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes, and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

Disease: HER2-positive solid tumors

Therapeutic area: Cancer - Oncology

Country:

Trial details:

• The trial is a multicenter, open-label, Phase I dose escalation study that is deisgned to determine the safety, tolerability and potential anti-cancer activity of PRS-343 in patients with advanced or metastatic HER2-positive solid tumors for which standard treatment options are not available, are no longer effective, are not tolerated, or the patient has refused standard therapy. The trial includes expansion cohorts.

Latest news:

• • On October 2, 2017, Pieris Pharmaceuticals announced that the first patient has been dosed in the Phase I clinical trial of PRS-343.
• • On August 9, 2017, Pieris announced that the company has received FDA acceptance of its IND filing for PRS-343.
• The company is now engaged with its clinical trial sites toward initiation of patient dosing in a Phase I study in patients with HER2-positive solid tumors.
• • On April 4, 2017,  Pieris Pharmaceuticals has presented data informing the design of a first-in-patient clinical trial for PRS-343, a first-in-class 4-1BB/HER2 bispecific antibody/Anticalin fusion protein, in a poster session at the 2017 Annual Meeting of the American Association for Cancer Research (AACR). Complementing previously disclosed preclinical data demonstrating that PRS-343 elicits robust T cell expansion in the tumor microenvironment while avoiding unwanted peripheral T cell activation in HER2-positive cancer models, the data presented today demonstrate:
• · PRS-343 elicited robust T cell activation when engaging HER2 on cell lines derived from tumors resistant to trastuzumab therapy, as well as tumor cell lines with elevated HER2 expression in the IHC 2+ range
• · 4-1BB-mediated T cell activation by PRS-343 resulted in the expression of a broad spectrum of inflammatory cytokines associated with anti-tumor immune responses
• · PRS-343 was well tolerated and led to no significant findings in IND-enabling preclinical safety and non-human primate toxicology studies.
• Pieris now anticipates to initiate clinical development of PRS-343 during the first half of 2017.
• • On September 26, 2016, Pieris Pharmaceuticals announced that it has presented new preclinical data demonstrating in vivo efficacy of PRS-343, at the 2016 CRI-CIMT-AACR International Cancer Immunotherapy Conference - Translating Science into Survival, taking place in New York City. The in vivo data show that treatment of HER2-positive tumor-bearing animals with PRS-343 provided dose-dependent, dual anti-tumor activity by increasing the frequency of tumor-infiltrating lymphocytes via bispecific targeting of 4-1BB and HER2, as well as mediating tumor growth inhibition by direct antagonism of HER2 on tumor cells.
• In contrast, an agonistic anti-4-1BB benchmark monoclonal antibody displayed neither tumor growth inhibition nor enhanced lymphocyte infiltration into tumors compared to an isotype control mAb, but preferentially activated T cells systemically, resulting in significant toxicity.
• Pieris is looking forward to the initiation of a phase 1 clinical trial of PRS-343 for the treatment of cancer patients planned for the first half of 2017.
• • On March 17, 2016, Pieris Pharmaceuticals announced that in vivo proof of concept data for anti-tumor activity of PRS-343 will be highlighted in a poster session at the 2016 Annual Meeting of the American Association for Cancer Research (AACR) in New Orleans, April 16-20, 2016. PRS-343 binds to CD137 (4-1BB) on T cells and HER2 on tumor cells, producing tumor-targeted immune activation.
• In a humanized mouse model engrafted with a HER2-positive human tumor cell-line and human peripheral blood mononuclear cells, treatment with PRS-343 led to tumor growth inhibition superior to that observed with either an isotype control or a benchmark CD137-targeting antibody. The data to be presented, which includes phenotyping of peripheral and intra-tumoral lymphocytes, support the intended mode of action of tumor-localized costimulatory T cell activation with an enhanced therapeutic index compared to anti-CD137 antibody approaches.
• • On September 21, 2015, Pieris Pharmaceuticals announced the presentation of new preclinical data for its Anticalin-based CD137/HER2 bispecific drug candidates in the PRS-343 immuno-oncology program. The data demonstrate potent CD137-driven T cell activation that is dependent upon drug-mediated HER2 engagement on the tumor cell surface. The data provide an overview of the drug-like properties and pharmacodynamic activity of four distinct CD137/HER2 bispecific molecules comprised of an anti-HER2 monoclonal antibody genetically linked to an agonist CD137-targeting Anticalin® protein. All four bispecific molecules demonstrated not only desired biophysical properties, but also the ability to activate T cells ex vivo as a function of HER2 engagement. Importantly, the unique geometries of each drug candidate led to pronounced differences in levels of T cell activation, highlighting the importance of structure in designing bispecifics.

     

Is general: Yes