PY314 Treatment Begins in Phase 1B Study of Patients With Advanced Solid Tumors

The first patient has received PY314 in a phase 1b study, and patients with advanced solid tumor are being actively recruited as sites across the United States.

The investigational monoclonal antibody, PY314, has been administered to the first patient in a phase 1b expansion study, which is investigating its safety, tolerability, and pharmacokinetics in patients with advanced solid tumors, according to a press release by Pionyr Immunotherapeutics, Inc.1

PY314 works by binding to TREM2 on the surface of myeloid cells that are immunosuppressive and tumorous. By design, the agent can eliminate the TREM2-expressing tumor-associated macrophages, achieving productive anti-tumor immunity. In preclinical studies, this mechanism of action was shown to activate CD8 T cells, natural killer cells, and M1-like macrophages to destroy tumors.

“Dosing the first patient in our phase 1b expansion study is an important milestone for the clinical development of PY314, having passed the first safety analysis and identifying a recommended dose for further evaluation,” said Leonard Reyno, MD, executive vice president and chief medical officer, Pionyr, in a press release. "PY314 represents an opportunity to expand immunotherapy options for patients with advanced solid tumors, which continues to represent a major unmet need, especially among patients with checkpoint resistant tumors. We are excited to begin this expansion study with leading clinical sites and investigators who have enthusiastically joined in this effort alongside us.”

In the open-label, phase 1b study (NCT04691375), treatment with single-agent PY314 will be assessed at 4 dose levels in patients with advanced solid tumors. In other experimental arms, PY314 will be evaluated in combination with pembrolizumab (Keytruda).2

The primary end point being explored in the study is the incidence of adverse events (AEs) and dose-limiting toxicities. The study will also assess pharmacokinetics, the incidence of anti-drug antibody formation, objective response rate, clinical benefit rate, and duration of response. Other outcomes of the study include progression-free survival and overall survival.

To be eligible for inclusion, patients with advanced solid tumors must be 18 years of age or older with a diagnostic tumor sample. Documented disease progression, measurable disease per RECISTs v1.1, and ECOG performance status ≤ 2, and adequate hematologic, hepatic, and renal function. Patients are also required to have recovered from any toxicities related to a prior antitumor activity.

Patients are excluded from the study if they are candidates for targeted therapy, have a history of autoimmune disorder that requires treatment with intermittent disease-modifying therapy, stable treated or asymptomatic brain metastases for a minimum of 3 months, uncontrolled intercurrent illness, decompensated liver illness, and cardiac disease within 12 months of the first dosing in the study. In terms of prior treatment, patients cannot enroll in the study if they have received anti-cancer therapy.

Individuals with advanced solid tumors who meet the inclusion criteria are being actively recruited at sites in Arizona, Colorado, Florida, Michigan, Minnesota, Tennessee, and Texas.

“PY314 is intended to clear the way for pro-inflammatory, anti-tumor immune cells to take control of the tumor microenvironment and destroy tumor cells,” said Alicia Levey, PhD, chief pperating officer, Pionyr, in the press release.1 “As a further demonstration of our Myeloid TuningTM platform, we also expect to initiate an expansion study in the first half of 2022 of our PY159 program, which ‘turbocharges’ anti-tumor activity by reprogramming TREM1-expressing immunosuppressive myeloid cells.”

References:

1. Pionyr Immunotherapeutics doses first patient in phase 1b expansion study of PY314. News release. Pionyr Immunotherapeutics. March 8, 2022. Accessed March 11, 2022. https://bit.ly/3tOJ2IW

2. A study of PY314 in subjects with advanced solid tumors. Clinicaltrials.gov. Accessed March 11, 2022. https://bit.ly/3KByN1f