FDA Grants Orphan Drug Designation to PT217 for Neuroendocrine Carcinoma
Currently, the drug will be studied in the SKYBRIDGE (NCT05652686) trial, a first-in-human, phase 1/2, open-label, dose-escalation and expansion study.
The FDA granted orphan drug designation (ODD) to PT217 (Phanes Therapeutics, Inc) for the treatment of neuroendocrine carcinoma (NEC).1
The drug is a first-in-class bispecific antibody targeting delta-like ligand 3 and cluster of differentiations 47. It was also granted ODD for the treatment of small cell lung cancer (SCLC) in 2022 and fast track designation in 2024 for extensive-stage SCLC with disease progression following platinum chemotherapy with or without checkpoint inhibitors. The drug will also be investigated in combination with atezolizumab (Roche).1
Image Credit: Juan Gärtner - stock.adobe.com
NEC tumors affect the nerve cells and hormones, and they can develop anywhere that endocrine cells are present, including the lungs, small intestine, and pancreas. The symptoms of the tumors can fall into 2 categories: hormonal symptoms, including severe diarrhea, severe gastric ulcer, or controlled blood sugar that responds poorly to treatment; and mechanical symptoms, including small bowel obstruction or pain in a particular place and are related to the function of 1 body part. It is estimated that 12,000 individuals in the US will be diagnosed with neuroendocrine tumors each year.2
The drug will be studied in the SKYBRIDGE (NCT05652686) trial, which is a first-in-human, phase 1/2, open-label, dose-escalation and expansion study. Investigators will evaluate the safety, tolerability, pharmacodynamics, and preliminary efficacy of the drug in the NEC patient population. To be eligible, patients will be screened for SCLC, large cell neuroendocrine carcinoma (LCNEC) of the lung, and extrapulmonary neuroendocrine carcinoma (EP-NEC), including neuroendocrine prostate cancer, and gastroentero-pancreatic neuroendocrine carcinoma.3
To be included, standard therapy must have proved to be ineffective, intolerable, or inappropriate, or individuals must have progressed after standard therapy. Patients will also be 18 years and older and have measurable disease defined by RECIST v1.1 for solid tumors. Exclusion criteria include women who are pregnant or lactating, those with autoimmune diseases requiring systemic treatment past 12 months, patients with uncontrolled hypertension, and patients with HIV.3
Investigators will use a 3+3 dose escalation, with a starting dose of PT217 0.2 mg/kg weekly and provisional dose levels of 0.6 mg/kg, 2 mg/kg, 6 mg/kg, and 12 mg/kg weekly. The cohort will be split into 2 dose expansions, with one including SCLC, LCNEC, and EP-NEC and the other including SCLC and LCNEC.4
The primary end points included determining the dose-limiting toxicity by monitoring grade 3 or higher adverse events, the maximum tolerated dose by monitoring the dose-limiting toxicities in 3 to 6 individuals in each cohort, the recommended phase 2 dose by monitoring the maximum tolerated dose and minimal efficacious dose, and the safety of PT217, according to the clinical trial information. Secondary outcomes include objective response rate, disease control rate, progression free survival, 6-month overall survival, the pharmacokinetics of PT217 by the Area Under the Curve, maximum concentration, time of maximum concentration, half-life, median residence time, and volume of distribution.4
