FDA Grants Fast Track Status to PT886 for Metastatic Claudin 18.2+ Pancreatic Adenocarcinoma

FDA

The FDA has granted fast track designation to PT886 for use as a potential therapeutic option in patients with metastatic claudin 18.2–positive pancreatic adenocarcinoma, according to an announcement from Phanes Therapeutics, Inc.¹

The native IgG-like bispecific antibody, which targets claudin 18.2 and CD47, was developed utilizing the platforms PACbody and SPECpair. The agent kills tumor cells through antibody-dependent cellular cytotoxicity and phagocytosis.² Preclinical data have indicated in vitro and in vivo activity. The safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT886 is under investigation in the first-in-human phase 1/2 TWINPEAK study (NCT05482893), which is currently recruiting.³

“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,” Ming Wang, founder and chief executive officer of Phanes Therapeutics, stated in a press release.¹ “PT886 is a product of Phanes’ ingenious innovation in creative design of both novel therapeutic approaches and practical technologies.”

The phase 1/2, open-label, dose-escalation and -expansion study is enrolling patients who are at least 18 years of age.³ To participate in parts A and B, patients need to have unresectable advanced or metastatic solid gastric, gastroesophageal junction (GEJ), or pancreatic tumors who received prior treatment for advanced disease or disease for which treatment is not available or not tolerated.

To enroll in parts B, C, and D, patients must have claudin 18.2 positivity of at least 10% in tumor tissue, except for cohorts 2 and 4 of parts C and D, respectively; for those cohorts, the cutoff is subject to change based on emerging data. Those enrolling to cohort 5 in part D are required to have claudin 18.2 positivity of at least 10% in tumor tissue following previous treatment with zolbetuximab. Cohort 2 in part C will need to have pancreatic ductal adenocarcinoma who are treatment naive for metastatic or advanced disease and who do not have a contraindication for gemcitabine/nab-paclitaxel (Abraxane).

In part D, cohort 3 requires patients with metastatic or advanced gastric or GEJ cancer who progressed on first- or second-line standard chemotherapy with or without immune checkpoint inhibitors and have not been exposed to claudin 18.2–targeted agents. In this part, cohort 4 will include those with metastatic or advanced HER2-negative gastric or GEJ cancer that are naive for metastatic/advanced disease. Cohort 5 in this part requires patients to have metastatic or advanced gastric or GEJ cancer that progressed under frontline standard chemotherapy and zolbetuximab; these patients cannot have prior exposure to pembrolizumab (Keytruda) or other immune checkpoint inhibitors for their metastatic or advanced disease.

For the dose-escalation portion of the study, investigators will utilize an accelerated titration design where 1 patient will be enrolled at the dose levels of 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg. The standard 3+3 design will be implemented for dose level 4, which is 3 mg/kg. In the dose-expansion portion of the study, 2 dose levels of PT886 will be evaluated: the recommended dose for expansion from part A and another level. Regimens given once every 2 weeks and/or once every 3 weeks may also be assessed.

For part C, those in cohort 1 will be given PT886 plus paclitaxel, and those in cohort 2 will be given PT886 plus gemcitabine and nab-paclitaxel. For part D, those in cohort 3 will be given PT886 with pembrolizumab, those in cohort 4 will be given PT886 plus standard chemotherapy and pembrolizumab, those in cohort 5 will be given PT886 with pembrolizumab.

The primary outcome measures of the study are to examine dose-limiting toxicities, the maximum tolerated dose, the recommended phase 2 dose of PT886. Secondary outcome measures include evaluating the pharmacokinetics, the immunogenicity, and the preliminary efficacy of the study drug. Investigators will also assess pharmacodynamic markers and pretreatment claudin 18.2 expression as it relates to primary end points.

The trial plans to enroll an estimated 114 patients, and the primary completion of the trial is estimated to be December 2025.

In June 2022, the FDA granted PT886 an orphan drug designation for patients with pancreatic cancer.⁴

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://www.phanesthera.com/news/phanes-therapeutics-pt886-granted-fast-track-designation-for-the-treatment-of-patients-with-metastatic-claudin-18-2-positive-pancreatic-adenocarcinoma-by-the-fda/
2. Overman MJ, Melhem R, Blum-Murphy MA, et al. A phase I, first-in-human, open-label, dose escalation and expansion study of PT886 in adult patients with advanced gastric, gastroesophageal junction, and pancreatic adenocarcinomas. J Clin Oncol. 2023;41(suppl 4):TPS765. doi:10.1200/JCO.2023.41.4_suppl.TPS765
3. PT886 for treatment of patients with metastatic/advanced gastric, gastroesophageal junction and pancreatic adenocarcinoma (the TWINPEAK study). ClinicalTrials.gov. Updated March 1, 2024. Accessed March 21, 2024. https://clinicaltrials.gov/study/NCT05482893
4. Phanes Therapeutics’ PT886 granted orphan drug designation for the treatment of pancreatic cancer by the FDA. News release. Phanes Therapeutics, Inc. June 30, 2022. Accessed March 21, 2024. https://www.phanesthera.com/news/phanes-therapeutics-pt886-granted-orphan-drug-designation-for-the-treatment-of-pancreatic-cancer-by-the-fda/