FDA Lifts Partial Clinical Hold on Phase 1 Studies of PRS-343 for Solid Tumors

The FDA has lifted a partial clinical hold on the phase 1 clinical trials of PRS-343 for solid tumors.

The FDA has lifted a partial clinical hold on the phase 1 clinical trials of PRS-343 for solid tumors, Pieris Pharmaceuticals, Inc., announces in a press release.1

"It has been rewarding to see the impact of PRS-343 on the lives of patients in these studies. Data continue to be encouraging, and the clinical benefit linked to single-agent activity that we have seen attests to the potential of this therapy and, more broadly, our localized 4-1BB agonism approach," said Stephen S. Yoder, president, and chief executive officer of Pieris Pharmaceuticals, in a statement. "We are excited to advance this program into the proof-of-concept phase and look forward to sharing more details about the study later this quarter."

The studies were placed on hold in July 2020, at which time the FDA requested a confirmatory laboratory-based in-use and compatibility study of the drug; the FDA did not cite adverse events (AEs) related to the request. Patients who were enrolled to the studies were allowed to continue receiving the therapy, but no new patients were allowed to enroll until the partial clinical hold was lifted.2

Among the studies halted, the open-label dose-escalation phase 1b trial (NCT03650348) is exploring the safety and efficacy of PRS-343 in combination with atezolizumab (Tecentriq) in previously treated advanced or metastatic HER2-positive solid tumors, such as bladder, breast, and gastrointestinal (GI). The dose-escalation portion of the study will be followed by an expansion period.

The primary end point of this study is the incidence of dose-limiting toxicities. Secondary end points include the overall response rate, duration of response, rate of complete response, incidence and severity of AEs, peak plasma concentration, area under the plasma concentration versus time curve, and time to maximum dose concentration, as well as terminal half-life and presence and/or concentration of anti-PRS-343 and anti-atezolizumab antibodies.

A multicenter open-label phase 1 dose-escalation study with an expansion cohort (NCT03330561) was designed to determine the maximum tolerated dose of PRS-343, as well as the recommended phase 2 dose and dosing schedule in patients with HER2-positive advanced or metastatic solid tumors. The primary end point of the study is the incidence and severity of AEs. The expansion cohort of this study will include patients with locally advanced or metastatic HER2-positive solid tumors, such as gastric/gastroesophageal/esophageal, breast, and bladder cancer.


1. FDA lifts partial clinical hold on PRS-343 phase 1 studies. News Release. Pieris Pharmaceuticals, Inc. January 19, 2021. Accessed January 20, 2021. https://bit.ly/3bXg9Da

2. Pieris pharmaceuticals announces partial clinical hold on PRS-343. Pieris Pharmaceuticals, Inc. July 20, 2020. Accessed January 20, 2021. https://bit.ly/3itlZx4