FDA fast tracks PT217 for neuroendocrine prostate cancer

The FDA has granted a fast track designation to PT217, a DLL3- and CD47-targeting first-in-class native IgG-like bispecific antibody for the treatment of patients with metastatic de novo or treatment-emergent neuroendocrine prostate cancer, Phanes Therapeutics announced in a news release.¹

Primary completion of the study is anticipated by December 2027.

In August 2024, the FDA also granted an orphan drug designation to PT217 for the management of neuroendocrine carcinoma.²

The agent is currently under investigation for the treatment of patients with neuroendocrine cancers, including neuroendocrine prostate cancer, as well as small cell lung cancer (SCLC). The therapy was granted a fast-track designation earlier this year for extensive-stage SCLC, and an orphan drug designation for this indication in 2022.

The phase 1/2 SKYBRIDGE trial (NCT05652686) is currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT217 as a monotherapy or in combination with chemotherapy and/or an immune checkpoint inhibitor (ICI) in patients with DLL3-expressing neuroendocrine cancers.³

In total, the first-in-human, open-label study plans to enroll 203 adult patients across 7 clinical trial sites in the United States. To be eligible for enrollment, patients need to have an ECOG performance status of 0 or 1 and adequate organ function, among other disease- and cohort-specific measures.

Patients are excluded from the study in part if they are pregnant or lactating, have an autoimmune disease requiring systemic treatment, have impaired cardiac function or significant diseases, or have grade 3 or higher neuropathy, plus additional measures.

The trial will consist of a dose escalation phase (Part A), a dose expansion phase (Part B), and a chemotherapy combination phase (Part C) and an ICI combination therapy phase (Part D).

In Part D, PT217 will be administered in combination with atezolizumab (Tecentriq) with or without chemotherapy (carboplatin plus etoposide). Phanes recently entered into a clinical supply agreement with Roche earlier this year to support assessment of PT217 in combination with atezolizumab in the SKYBRIDGE study.⁴

The primary outcome measures for the trial are the determination of dose-limiting toxicities, a maximum tolerated dose, and a recommended phase 2 dose, as well as safety and tolerability, all assessed through study completion. Secondary outcome measures are the pharmacokinetics, immunogenicity, and preliminary efficacy of PT217 in this patient population.

Primary completion of the study is anticipated by December 2027, with final completion planned for August 2028.

In addition to the SKYBRIDGE trial, a phase 1 study of PT217 is also ongoing in China (CTR20242720).

References

1. Phanes Therapeutics' PT217 granted Fast Track Designation by the FDA for NEPC. News release. Phanes Therapeutics. December 4, 2024. Accessed December 5, 2024. https://www.phanesthera.com/news/phanes-therapeutics-pt217-granted-fast-track-designation-by-the-fda-for-nepc/

2. Phanes Therapeutics’ PT217 receives Orphan Drug Designation for neuroendocrine carcinoma from the FDA. News release. Phanes Therapeutics. August 16, 2024. Accessed December 5, 2024. https://www.phanesthera.com/news/phanes-therapeutics-pt217-receives-orphan-drug-designation-for-neuroendocrine-carcinoma-from-the-fda/

3. A study of PT217 in patients with neuroendocrine carcinomas expressing DLL3 (the SKYBRIDGE study). ClinicalTrials.gov. Last updated November 22, 2024. Accessed December 5, 2024. https://clinicaltrials.gov/study/NCT05652686

4. Phanes Therapeutics, Inc. announces clinical supply agreement with Roche to evaluate PT217 in combination with an anti-PD-L1 therapy. News release. Phanes Therapeutics. May 8, 2024. Accessed December 5, 2024. https://www.phanesthera.com/news/phanes-therapeutics-inc-announces-clinical-supply-agreement-with-roche-to-evaluate-pt217-in-combination-with-an-anti-pd-l1-therapy/