Alkermes issued the following announcement on June 12.
Alkermes plc (Nasdaq: ALKS) today announced the initiation of the monotherapy expansion stage of its ARTISTRY-1 clinical trial to evaluate the efficacy, safety and tolerability of ALKS 4230 in treating patients with renal cell carcinoma or melanoma. Initiation of this portion of the ongoing study follows the identification of 6 µg/kg/day administered intravenously as the recommended monotherapy dose of ALKS 4230 to evaluate in these select tumor types. The maximum tolerated dose of ALKS 4230 has not yet been reached, and the dose-escalation stage of the ARTISTRY-1 study is continuing. ALKS 4230 is a novel, engineered fusion protein designed to selectively expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex.
"At the 6 µg/kg/day dose, data from the dose-escalation stage of ARTISTRY-1 demonstrated the tolerability profile we set out to achieve for ALKS 4230, along with desired lymphocyte cell expansion without corresponding Treg activation. This validates our design rationale for ALKS 4230, and we now look forward to progressing into the expansion stage to evaluate ALKS 4230 as monotherapy in select tumor types," said Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "We plan to present the first efficacy data from across the ALKS 4230 development program at a medical meeting later this year, pending conference acceptance."
Selection of the recommended phase 2 dose of ALKS 4230 as monotherapy was made following the completion of five dose-escalation cohorts, spanning a dose range of 0.1 µg/kg/day to 6 µg/kg/day, in 36 patients who were refractory to prior administered therapies known to demonstrate clinical benefit. Data from the completed cohorts demonstrated dose-dependent pharmacodynamic effects on circulating natural killer (NK) cells and CD8+ T cells, and minimal and non-dose dependent effects on immunosuppressive regulatory T cells (Tregs). The newly initiated monotherapy expansion stage will assess objective efficacy measures of ALKS 4230 administered intravenously daily for five consecutive days in up to 105 patients refractory to prior administered therapies with renal cell carcinoma or melanoma, two tumor types for which high-dose IL-2 has demonstrated durable anti-tumor responses as a monotherapy treatment.1
Data from the initial four cohorts of the dose-escalation stage of ARTISTRY-1 were presented at the 2018 Society for Immunotherapy of Cancer (SITC) Annual Meeting. Treatment with ALKS 4230 at 3 µg/kg/day resulted in a dose-dependent increase in circulating NK cells and CD8+ T cells with a near 4-fold and 2-fold expansion, respectively, and minimal, non-dose-dependent change in Tregs. Further effector-cell expansion was observed in cohort 5 at the 6 µg/kg/day dose, with minimal increase in circulating Tregs. No dose-limiting toxicities were observed in cohort 5. Fever and chills were the most common treatment-related adverse events (AEs) for ALKS 4230 across all cohorts, and the safety profile observed with ALKS 4230 was consistent with the known profile of cytokine therapy.
Original source can be found here.