FDA Fast Tracks PT886 in CLDN18.2+ Pancreatic Cancer

• PT886, a novel drug being developed for the treatment of several cancers, including pancreatic adenocarcinoma, received a fast track designation from the FDA.
• The agent works by targeting 2 specific proteins, claudin (CLDN) 18.2 and CD47, on cancer cells.
• A phase 1 clinical trial titled the TWINPEAK study (NCT05482893) is currently underway to assess the agent’s safety, efficacy, and tolerability.

The FDA has granted a fast track designation to PT886, a first-in-class native IgG-like bispecific antibody, for metastatic CLDN18.2-positive pancreatic adenocarcinoma treatment.¹

PT886 works to target CLDN18.2 and CD47 and was created using proprietary bispecific antibody platforms from Phanes Therapeutics Inc., called PACbody and SPECpair. The agent is undergoing development for the treatment of gastric, gastroesophageal junction, and pancreatic adenocarcinomas.

Previously, in 2022, the FDA granted PT886 an orphan drug designation for the treatment of patients with pancreatic cancer.

In the TWINPEAK study, a multicenter, phase 1 trial, investigators are assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT886 in patients with locally advanced or metastatic gastric, gastroesophageal junction and pancreatic cancers. The first patient was dosed with PT886 in the phase 1 study in March 2023.

"PT886 has the potential to be a transformative treatment option for patients with metastatic claudin 18.2-positive pancreatic adenocarcinoma, for which current standard of care is insufficient," said Ming Wang, founder and chief executive officer of Phanes Therapeutics, in a press release. "PT886 is a product of Phanes' ingenious innovation in creative design of both novel therapeutic approaches and practical technologies."

Pancreas or pancreatic cancer with organs and tumors or cancerous cells 3D rendering illustration with male body. Anatomy, oncology, disease, medical: © matthieu - stock.adobe.com

About the TWINPEAK Study of PT886

Enrollment in the phase 1 study is open to patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic gastric, gastroesophageal junction, and pancreatic cancers. Their disease must have progressed after all available standard therapy or for which standard therapy has shown to be ineffective, intolerable, or inappropriate.² Patients are required to have measurable disease, including at least 1 lesion amenable to response assessment per RECIST 1.1 criteria, adequate organ function, and an ECOG performance status of 0 to 1. All acute adverse events that emerged from prior cancer therapies must be resolved to grade ≤ 1 or baseline, excluding alopecia or neuropathy.

The study is utilizing a standard 3+3 dose-escalation design. The starting dose being evaluated is PT886 monotherapy 0.1 mg/kg given weekly, and other provisional dose levels include: 0.3 mg/kg weekly, 1 mg/kg weekly, 3 mg/kg weekly, and 6 mg/kg weekly. Then, the dose-expansion portion of the trial will evaluate 2 doses of PT886 as determined from the escalation phase.

Determining the dose-limiting toxicities, maximum tolerated dose, and recommended phase 2 dose of PT886 make up the primary end points of the study. Preliminary efficacy, as assessed by objective response rate, pharmacokinetics, and immunogenicity are the secondary end points being studied.

The trial has an estimated completion date of April 2026 and an estimated enrollment of 114 patients. The study is actively recruiting in Colorado, Massachusetts, Texas, and Virginia.

REFERENCES:

1. Phanes Therapeutics' PT886 granted Fast Track designation for the treatment of patients with metastatic claudin 18.2-positive pancreatic adenocarcinoma by the FDA. News release. Phanes Therapeutics, Inc. March 20, 2024. Accessed March 21, 2024. https://tinyurl.com/48xjepcp

2. PT886 for treatment of patients with advanced gastric, gastroesophageal junction and pancreatic adenocarcinoma. ClinicalTrials.gov. Updated March 1, 2024. Accessed March 24, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05482893