A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors

Area of Science:

• Oncology
• Pharmacology

Background:

• Delta-like protein 3 (DLL3) is a promising therapeutic target due to its high expression in neuroendocrine carcinomas/neuroendocrine tumors (NEC/NET) and other solid malignancies.
• Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate specifically designed to target DLL3.

Purpose of the Study:

• To evaluate the safety and preliminary efficacy of Rovalpituzumab tesirine (Rova-T) in patients with advanced solid tumors expressing Delta-like protein 3 (DLL3).
• To determine the recommended Phase II dose (RP2D) for Rova-T in this patient population.

Main Methods:

• A Phase I/II clinical trial (NCT02709889) enrolled 200 patients with NEC/NET or other DLL3-expressing solid tumors.
• Patients received Rova-T at various doses, with the RP2D established at 0.3 mg/kg every 6 weeks for two cycles.
• Safety was assessed by monitoring adverse events, and efficacy was evaluated by objective response rates.

Main Results:

• The recommended Phase II dose (RP2D) of Rovalpituzumab tesirine (Rova-T) was determined to be 0.3 mg/kg every 6 weeks.
• Grade 3/4 adverse events at the RP2D included anemia (17%), thrombocytopenia (15%), and elevated aspartate aminotransferase (8%), indicating manageable toxicity.
• Antitumor activity was observed, with an overall response rate of 10% (15/145 patients) at the RP2D, including 13% (9/69) in the NEC/NET subgroup.

Conclusions:

• Rovalpituzumab tesirine (Rova-T) demonstrates manageable toxicity and promising antitumor activity in patients with advanced Delta-like protein 3 (DLL3)-expressing solid tumors, particularly NEC/NET.
• The established RP2D of 0.3 mg/kg every 6 weeks supports further investigation of Rova-T in Phase II and subsequent trials for relevant cancer types.