Phase 1b Expansion Study of PY159 Doses First Patient With Ovarian Cancer

Enrollment has begun in the phase 1b trial examining PY159 alone and in combination with pembrolizumab in patients with unresectable and/or metastatic solid tumors that are refractory or relapsed to standard of care.

The first patient has been dosed with single-agent PY159 in the ovarian cancer cohort of the phase 1b expansion portion of a randomized, open-label study (NCT04682431).

PY159 is an afucosylated humanized monoclonal antibody which binds human triggering receptors expressed on myeloid cells 1 (TREM1). Preclinical studies have shown PY159 to effectively induce signaling through the TREM1–DAP12 complex, leading to downstream phosphorylation, and an increase in production of cytokines and chemokines, and the upregulation of costimulatory and activation markers. The agent converts suppressive tumor-associated myeloid cell populations into inflammatory cells which then promotes anti-tumor immune responses.

The phase 1a/1b trial will examine PY159 alone and in combination with pembrolizumab (Keytruda) in patients with ovarian cancer, pancreatic ductal adenocarcinoma, non–small cell lung cancer, triple-negative breast cancer, hormone receptor-positive, HER2-negative breast cancer, head and neck squamous cell carcinomas, and colorectal cancer.

"We developed PY159 to target TREM1 and reprogram myeloid cells within the tumor microenvironment to promote anti-tumor responses – a novel approach to TREM1 biology for anti-tumor drug development," said Leonard Reyno, MD, executive vice president, and chief medical officer of Pionyr Immunotherapeutics, Inc, in the press release. "In the phase 1a dose escalation study, PY159 was well tolerated in doses up to 10 mg/kg and showed dose-proportional pharmacokinetics. With these conclusions from phase 1a, we are excited to begin this phase 1b expansion study with leading clinical sites and investigators."

In full, the phase 1a/1b study of PY159 alone or in combination with pembrolizumab aims to evaluate PY159 in subjects with locally advanced, unresectable and/or metastatic solid tumors that are refractory or relapsed to standard of care. In part A, the dose escalation portion of the study, PY159 will be administered alone and in combination with pembrolizumab in a standard 3 + 3 design. Part B is the dose expansion portion of the trial where 1 or more dose levels of PY159 will be administered alone and in combination with pembrolizumab for predefined tumor histologies.

Patients aged 18 years and older with solid tumor diagnoses as confirmed by cytology or histology are eligible for enrollment in the trial. Subjects must provide an original, diagnostic tumor sample to determine TREM1 gene expression, have documented radiographic disease progression that includes prior treatment with a CPI, measurable disease by RECIST 1.1., resolved all acute toxic effects of any prior antitumor therapy, including immunotherapy, to grade < 2 before the start of study drug dosing, and an ECOG performance status of ≤ 2. There is no limit to the number of prior treatments

The primary end point of the study is incidence of adverse events with the additional end point of determining the dose-limiting toxicity of PY159 in part A of the trial. The study will also evaluate the safety, tolerability, and pharmacokinetics of PY159. In addition, exploratory biomarkers will be evaluated, including analysis of TREM1 gene expression in the immune infiltrate of tumor biopsy samples.

The trial has an estimated study completion date of April 7, 2023, and is currently enrolling in Colorado, Connecticut, Massachusetts, Michigan, Oregon, and Texas.

References:
Pionyr immunotherapeutics doses first patient in phase 1b expansion study of PY159. News release. Pionyr Immunotherapeutics, Inc. September 20, 2022. Accessed September 21, 2022. https://yhoo.it/3SnOflu
A phase 1a/1b FIH study of PY159 and in combination with pembrolizumab in subjects with advanced solid tumors. ClinicalTrials.gov. Updated May 19, 2022. Accessed September 21, 2022. https://clinicaltrials.gov/ct2/show/NCT04682431?term=NCT04682431&draw=2&rank=1