On April 25, 2023 Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), reported that the first patient has been dosed with PRTH-101 in a Phase 1, first-in-human clinical trial for patients with immune-excluded solid tumors (Press release, Parthenon Therapeutics, APR 25, 2023, View Source [SID1234630502]).
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PRTH-101 is a first-in-class Discoidin Domain Receptor 1 (DDR1) antagonist monoclonal antibody that is expressed at very high levels in solid tumors with low levels of T cell infiltration. PRTH-101 is the first development candidate from Parthenon’s broad TME-focused pipeline to enter clinical development. PRTH-101 uniquely targets DDR1 and has demonstrated, in preclinical models, anti-tumor activity as a single agent and in combination with an anti-PD-1 checkpoint inhibitor.
"The initiation of a Phase 1 trial for PRTH-101 is an important step forward for cancer patients with DDR1-associated tumors, immune-excluded solid tumors, that have been shown to respond poorly to existing immuno-therapies," said J. Paul Eder, MD, Chief Medical Officer of Parthenon Therapeutics. "With no FDA-approved therapies that target DDR1-associated tumors, we believe that PRTH-101 could uniquely improve patient outcomes by breaking down the barrier that various types of tumors construct to protect them from immune attack. Parthenon continues to focus on an unmet need in cancer that hasn’t been successfully targeted therapeutically, namely, direct modulation of the tumor microenvironment to overcome immune exclusion."
About PRTH-101
PRTH-101 is a therapeutic antibody that specifically binds to and blocks DDR1, a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and naturally attack the tumor. The creation of DDR1-directed collagen alignment does not appear to have a normal physiological surrogate and may therefore be unique to pathologies such as neoplasia, potentially allowing for relatively safe interventions. Thus, blockade of DDR1 represents a unique and "orthogonal" approach to stimulating the immune-based antitumor activity, and such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade.
Tumor types which show particularly high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1.
About the Phase 1 Trial
The Phase 1 trial (NCT05753722) is a multi-center, open-label, dose escalation and dose expansion study that is expected to enroll up to 270 patients in the US with advanced or metastatic solid tumors. The goals of the study are to assess safety and tolerability of PRTH-101, evaluate anti-tumor activity in select indications alone and in combination with anti-PD-1 inhibitors, and determine dosing regimens for the Phase 2 clinical program. In addition to examining the clinical profile of PRTH-101, the trial will evaluate DDR1 and pathway-related proteins as predictive biomarkers for patients whose tumors respond to treatment.