FDA Grants Fast Track Designation to PT217 for Neuroendocrine Prostate Cancer

The FDA has granted fast track designation to PT217 for the treatment of patients with metastatic de novo or treatment-emergent neuroendocrine prostate cancer.1

PT217 is a first-in-class native IgG-like bispecific antibody that targets DLL3 and CD47. The agent is under investigation in the multicenter, dose-escalation and -expansion, multicohort phase 1/2 SKYBRIDGE trial (NCT05652686), which is investigating PT217 as monotherapy or in combination with atezolizumab (Tecentriq) in patients with advanced or refractory DLL3-expressing cancers, including small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (NEC) of the lung (LCNEC), and extra-pulmonary NEC (EP-NEC).2

In the ongoing part A/phase 1 monotherapy dose-escalation portion of the trial, patients receive PT217 monotherapy at 1 of 6 dose levels (0.2 mg/kg weekly [n = 3-6]; 0.6 mg/kg weekly [n = 3-6]; 2 mg/kg weekly [n = 3-6]; 4 mg/kg every 2 weeks [n = 3-6]; 6 mg/kg every 2 weeks [n = 3-6]; and 12 mg/kg every 2 weeks [n = 6]). The end points of this portion are safety and tolerability, identification of the recommended dose for expansion, pharmacokinetics, disease control rate (DCR), 6-month overall survival (OS) rate, and biomarkers.

In the part A/phase 1/2 PT217 monotherapy dose-expansion backfill portion, patients will be assigned to 1 of 3 cohorts. Cohort 1 (n = 10-20) includes patients with EP-NEC or LCNEC who have progressed on or relapsed following frontline therapy. Cohort 2 (n = 10-20) includes patients with extensive-stage SCLC (ES-SCLC) who have progressed on first-line therapy that may have included an immune checkpoint inhibitor. Cohort 3 (n = 10-20) includes patients with EP-NEC or LCNEC who have completed frontline induction chemotherapy, have stable disease (SD) or partial response (PR) prior to enrollment, and are eligible to continue with PT217 maintenance therapy. The primary end point of this portion is progression-free survival (PFS). The secondary end points are DCR, overall response rate (ORR), 6-month OS rate (cohorts 2 and 3), OS (cohort 1), and safety. Biomarkers are an exploratory end point.

In the part B/phase 2 portion, patients will be assigned to 1 of 3 cohorts and will receive PT217 plus atezolizumab. Cohort 4 (n = 15) includes patients with ES-SCLC who have progressed on frontline treatment that may have included an immune checkpoint inhibitor. Cohort 5 (n = 15) includes patients with ES-SCLC who have completed frontline induction therapy with platinum-based chemotherapy plus an immune checkpoint inhibitor, have SD or PR prior to enrollment, and are eligible for combination therapy with PT217 and atezolizumab. Cohort 6 (n = 15) includes patients with EP-NEC or LCNEC who have progressed on frontline therapy. The primary end point of this portion is PFS. The secondary end points are DCR, ORR, 6-month OS rate (cohorts 4 and 5), OS (cohort 5), and safety. Biomarkers serve as an exploratory end point.

SKYBRIDGE is currently enrolling in the United States across all 7 open sites. The starting dose for part B will be optimized based on emerging data from part A phase 1.

PT217 is also under investigation in an ongoing phase 1 clinical trial (CTR20242720) in China.1

This is the second fast track designation that PT217 has received from the FDA. In April 2024, the agent received this designation for the treatment of patients with ES-SCLC who have disease progression after platinum chemotherapy with or without a checkpoint inhibitor. In June 2022 and August 2024, PT217 was also granted FDA orphan drug designation for the treatment of patients with SCLC and NEC, respectively.

References

1. Phanes Therapeutics’ PT217 granted fast track designation by the FDA for NEPC. News release. Phanes Therapeutics, Inc. 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. Sands J, Henry J, Meador C, et al. SKYBRIDGE study: an open-label, multicenter, dose escalation and dose expansion phase I/II study of PT217 as a monotherapy and in combination with an atezolizumab, in patients with SCLC, LCNEC and EP-NEC known to express DLL3. Ann Oncol. 2024;35(suppl 2):S1073-S1074. doi:10.1016/j.annonc.2024.08.1902