Phanes Therapeutics, a clinical-stage biotech company, has announced the dosing of the first patient in a clinical trial evaluating PT886, a first-in-class bispecific antibody, in combination with chemotherapy. This multi-center Phase I/II trial, known as the TWINPEAK study (NCT05482893), is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT886 in patients with locally advanced or metastatic gastric, gastroesophageal junction, and pancreatic cancers.
The initial dosing occurred in two cohorts: one for first-line treatment of pancreatic cancers and another for second-line treatment of gastric and gastroesophageal junction cancers. A separate cohort is evaluating PT886 in combination with pembrolizumab for gastric and gastroesophageal junction cancers.
PT886: A Novel Bispecific Antibody
PT886 is a native IgG-like bispecific antibody (bsAb) that simultaneously targets claudin 18.2 and CD47. Claudin 18.2 is a protein expressed in gastric and pancreatic cancers, while CD47 is a broadly expressed protein that can inhibit phagocytosis. By targeting both proteins, PT886 aims to enhance the immune system's ability to recognize and destroy cancer cells.
The FDA has granted PT886 Orphan Drug Designation (ODD) for the treatment of pancreatic cancer in 2022 and Fast Track designation for metastatic claudin 18.2-positive pancreatic adenocarcinoma earlier this year. These designations are intended to expedite the development and review of drugs for serious conditions.
TWINPEAK Study Design
The TWINPEAK study is an open-label, multi-center Phase I/II trial. It includes patients with locally advanced or metastatic gastric, gastroesophageal junction, and pancreatic cancers that have progressed after standard therapies or for whom standard therapies are ineffective, intolerable, or inappropriate. The Phase I portion of the study employs a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) and recommended Phase II dose. The primary endpoints include dose-limiting toxicities, MTD, and safety and tolerability. Preliminary efficacy, measured by objective response rate, is a key secondary endpoint.
Collaboration with Merck
Phanes Therapeutics has entered into a clinical collaboration agreement with Merck (known as MSD outside the US and Canada) to study PT886 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). This collaboration aims to explore the potential synergistic effects of combining PT886 with immune checkpoint inhibition.
A Phase I clinical trial of PT886 is also ongoing in China (CTR20241655), further expanding the evaluation of this novel bispecific antibody.
