Pieris Pharmaceuticals, Inc., a clinical-stage biotechnology company, announced that the first patient has been dosed in the phase 2 study of cinrebafusp alfa (PRS-343), a 4-1BB/HER2 Anticalin-based bispecific for the treatment of HER2-expressing gastric cancer.

The two-arm, multicenter, open-label phase 2 study is evaluating the efficacy, safety, and tolerability of cinrebafusp alfa in combination with ramucirumab and paclitaxel in patients with HER2-high gastric cancer and in combination with tucatinib in patients with HER2-low gastric cancer.

Patients in the phase 2 study will receive a loading dose of 18 mg/kg in week one and three, followed by maintenance doses of 8 mg/kg (Q2W) for both arms in the study. The Company is targeting an ORR of at least 40% with meaningful durability in the HER2-low arm, for which it intends to present data later this year. In the HER2-high arm, the Company is targeting an ORR of at least 50% with meaningful durability. Pieris intends to present data for the HER2-high arm in 2023. Collaboration partners Lilly and Seagen will supply ramucirumab and tucatinib, respectively, under previously announced drug supply agreements.

"The dosing of the first patient in this next phase of development of cinrebafusp alfa marks an important milestone for patients afflicted by gastric cancer without adequate treatment options, and we look forward to further evaluating the potential of this drug," said Tim Demuth, M.D., Ph.D., chief medical officer of Pieris. "We believe cinrebafusp alfa can provide differentiated treatment options for patients with gastric cancer via 4-1BB-mediated T-cell engagement, both in terms of efficacy and safety."

Cinrebafusp alfa (PRS-343) is a 4-1BB/HER2 fusion protein comprising 4-1BB-targeting Anticalin proteins and a HER2-targeting antibody. The drug candidate is currently in phase 2 development for the treatment of HER2-expressing solid tumours. In phase 1 studies, cinrebafusp alfa has shown an acceptable safety profile at all doses tested with no dose-limiting toxicities. The bispecific also showed a dose response and a 4-1BB-driven mechanism of action based on clinical benefit and pharmacodynamic correlates.

Pieris is a clinical-stage biotechnology company that combines leading protein engineering capabilities and deep understanding into molecular drivers of disease to develop medicines that drive local biology to produce superior clinical outcomes for patients.