REPLATINUM Phase III randomized study: RRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer.

RRx-001 is a cysteine-directed anticancer alkylating agent with activity in a Phase II study in platinum refractory small cell lung cancer. Here, we describe the design of REPLATINUM, an open-label, Phase III trial. 120 patients with previously platinum-treated small cell lung cancer in third line will be randomized 1:1 to receive RRx-001 followed by four cycles of a platinum doublet, and then alternating cycles of RRx-001 and single agent platinum until progression versus four cycles of a platinum doublet. At radiologic progression on the platinum doublet, patients may cross over to the RRx-001 arm. Primary objective: to demonstrate superior progression-free survival in the RRx-001 population. Secondary objectives: to demonstrate superiority for overall survival and objective response rate. Clinical Trial registration: NCT03699956.

A practical guide to the handling and administration of personalized transcriptionally attenuated oncolytic adenoviruses (PTAVs).

The aim of this review is to provide practical information on the handling, storage, and administration procedures for personalized oncolytic adenoviruses (PTAVs), which have recently entered clinical trials. As described herein, personalized oncolytic viruses refer to transcriptionally attenuated (TA) type 5 adenoviruses that are engineered to carry one or more neoantigenic transgenes derived from patient tumors. Vials of personalized viruses should be stored at -60°C without refreezing after thawing to maintain infectivity. To prevent accidental exposure and transmission, full implementation of universal precautions for preparation, administration, and handling is required. Contaminated materials that come into contact with personalized viruses should be properly disposed of in accordance with local institutional procedures. Severely immunocompromised or pregnant healthcare workers should not prepare or administer personalized viruses or directly contact injection sites. Personalized viruses are administered subcutaneously and intratumorally; however, only subcutaneous injection will be considered in this review. The specific storage, handling, administration, and safety requirements for personalized viruses are easily managed in the context of a clinical trial following the directives from the study protocol.