The AIDS Clinical Trials Group (ACTG) Protocol A5370, Version 1.0, 11/16/18, titled “Safety and Immunotherapeutic Activity of an Anti-PD-1 Antibody (Cemiplimab) in HIV-1-Infected Participants on Suppressive cART: A Phase I/II, Double-blind, Placebo-Controlled, Ascending Multiple Dose Study” was closed to accrual on October 28, 2019 (ClinicalTrials.gov Identifier: NCT03787095).
The study intended to enroll three dose groups of 15 participants in each group (12 receiving active therapy and 3 receiving placebo infusions). Eligible participants had well controlled HIV infection on antiretroviral therapy and CD4+ T cell counts >350 cells/mm3.
The study had enrolled five participants to the lowest dose group of 0.3 mg/kg IV for two doses 6 weeks apart. As per stringent protocol defined safety guidelines, the independent study monitoring committee (SMC) performed an ad hoc review when two potential immune-related, non-life-threatening adverse events were reported.
After careful review of unblinded data the SMC recommended that the protocol close to accrual and no further infusions be given to participants on study. All participants enrolled on the study and study sites have been notified about this new information.
Follow-up of all participants who received active study medication will proceed per protocol for continued safety monitoring.
The events were similar to adverse events reported in oncology studies at higher doses and with sustained dosing. Given the lack of expected direct benefit to study participants in A5370 and the frequency of the possibly immune-related events, accrual was closed. The implications of these results for other studies of anti-PD1 antibodies in people living with HIV should be considered in the context of the specific study, and the potential benefit to study participants