PT217 Gains FDA Orphan Drug Designation in Neuroendocrine Carcinoma

• The FDA has granted PT217 an orphan drug designation (ODD) for the treatment of neuroendocrine carcinoma.
• PT217 is a first-in-class bispecific antibody that targets delta-like ligand 3 (DLL3) and CD47.
• The agent was previously granted an ODD from the FDA for treating small cell lung cancer (SCLC) in 2022 and a fast track designation (FTD) in 2024 for extensive-stage SCLC (ES-SCLC).

An ODD was granted by the FDA to PT217, a first-in-class bispecific antibody targeting DLL3 and CD47, for the treatment of patients with neuroendocrine carcinoma.¹

PT217 is undergoing evaluation in the phase 1 SKYBRIDGE study (NCT05652686). Here, investigators are assessing the safety, tolerability, pharmacokinetics, and preliminary efficacy of PT217 in advanced or refractory cancers expressing DLL3.²

Patients with SCLC, large cell neuroendocrine carcinoma of the lung, and extrapulmonary neuroendocrine carcinoma, including but not limited to neuroendocrine prostate cancer and gastroenteropancreatic neuroendocrine carcinoma, are eligible for screening. Patients must have progressed after standard therapy or standard therapy has proven to be ineffective, intolerable, or is considered inappropriate.

Enrollment in the study is also open to patients with measurable disease by RECIST v1.1, those who have an ECOG performance status of 0 or 1, and those with adequate organ function. Patients must have resolved all adverse events from prior therapies and have a life expectancy of at least 3 months.

Patients who are pregnant or lactating, have autoimmune disease, have a known concurrent malignancy, or have uncontrolled hypertension are not eligible for participation in the trial.

The study consists of dose-escalation and dose-expansion phases. In the dose-escalation phase of the study, investigators aim to establish the recommended phase 2 dose (RP2D). The dose-expansion phase will include 2 cohorts, including 1 that will receive the RP2D and 1 that will receive 1 dose level lower.

The primary end points of the study are to evaluate dose-limiting toxicities, the maximum tolerated dose, the RP2D, and safety. Secondary end points include preliminary efficacy and pharmacokinetics. Disease control rate is an additional exploratory end point.

Patients at sites in Colorado, Massachusetts, Texas, and Virginia are being recruited for the study. The estimated enrollment of the trial is 52 patients, and the study has an anticipated completion date of June 2025.

In 2022, the FDA granted PT217 an ODD for the treatment of SCLC. More recently, in April 2024, the regulatory agency granted an FTD to the agent for the treatment of patients with ES-SCLC with disease progression following platinum chemotherapy with or without a checkpoint inhibitor.¹

Phanes Therapeutics, Inc. also entered into a clinical supply agreement with Roche earlier in 2024 to assess the combination of PT217 and atezolizumab (Tecentriq), an anti-PD-L1 therapy. In addition to PT217, the company is developing PT886, another first-in-class bispecific antibody that has been granted an ODD and FTD by the FDA, and PT199.

REFERENCES:

1. Phanes Therapeutics' PT217 receives orphan drug designation for neuroendocrine carcinoma from the FDA. News release. Phanes Therapeutics, Inc. August 16, 2024. Accessed August 16, 2024. https://tinyurl.com/32rb6pv9

2. A phase 1 study of PT217 in patients with advanced refractory cancers expressing DLL3 (the SKYBRIDGE study). ClinicalTrials.gov. Updated June 7, 2024. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT05652686