"The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while overcoming its limitations. These initial data from our phase 1 study demonstrate the unique mechanism of ALKS 4230, with dose-dependent pharmacodynamic effects on circulating natural killer cells and CD8+ T cells and minimal and non-dose dependent effects on immunosuppressive regulatory T cells," said
Details of the poster presentations at
- Abstract Poster #P423: "Safety, Pharmacokinetics and Pharmacodynamic Effects of ALKS 4230 in Patients With Advanced Solid Tumors From the Ongoing Dose Escalation Portion of a First-in-Human (FIH) Study," will be presented by
Ulka N. Vaishampayan , M.D.,Barbara Ann Karmanos Cancer Institute - ALKS 4230 was assessed in 24 patients with refractory solid tumors at doses ranging from 0.1 µg/kg/day to 3 µg/kg/day as part of the ongoing phase 1 study.
- Treatment with ALKS 4230 resulted in a dose-dependent increase in circulating natural killer (NK) cells and CD8+ T cells with a near 4-fold and 2-fold expansion, respectively, at 3 µg/kg/day, and minimal, non-dose-dependent change in regulatory T (Treg) cells.
- Fever and chills were the most common treatment-related adverse events (AEs) for ALKS 4230.
- These data support the rationale for assessing ALKS 4230 at the 3 µg/kg/day dose in combination with pembrolizumab, as well as for continued dose escalation in the monotherapy setting.
- Abstract Poster #P425: "Pharmacokinetics and Pharmacodynamic Effects of ALKS 4230, an Investigational Immunotherapeutic Agent, in
Cynomolgus Monkeys After Intravenous and Subcutaneous Administration ," will be presented byLei Sun , Ph.D.,Alkermes, Inc. - Data from two non-human primate studies demonstrated that subcutaneous administration of ALKS 4230 can achieve similar total systemic exposure of ALKS 4230 compared to intravenous administration, yet with less frequent dosing and a lower Cmax, leading to similar expansion of total CD8+ T cell and NK cell populations.
- These data support further clinical evaluation of subcutaneous administration of
ALKS 4230 as an alternative to intravenous dosing. - Abstract Poster #P123: "Peripheral Blood Lymphocyte Responses in Patients With Renal Cell Carcinoma Treated With High-Dose Interleukin-2," will be presented by
Wenxin Xu , M.D.,Beth Israel Deaconess Medical Center - Consistent with the known biological activities of IL-2, administration of high-dose IL-2 resulted in an approximate 2-fold expansion of circulating cytotoxic effector CD8+ T cells and NK cells and an approximate 4-fold expansion of circulating Treg cells.
- These data provide quantitative measures of the expansion of cytotoxic effectors such as CD8+ T cells and NK cells relative to Treg cells for high-dose IL-2, and may be useful in the future for evaluating possible differences in immune response to newer formulations of
IL-2.
Posters will be on display both
About the Phase 1 Study for ALKS 4230
The phase 1 study for ALKS 4230 includes three distinct stages: the ongoing monotherapy dose-escalation stage, the planned monotherapy dose-expansion stage and the recently initiated combination therapy stage with pembrolizumab. The dose-escalation stage is designed to determine a maximum tolerated dose of ALKS 4230 in a monotherapy setting and to identify the optimal dose range of ALKS 4230 based on measures of immunological-pharmacodynamic effects. Upon completion of the dose-escalation stage,
Anti-tumor response and duration of response assessments in the dose-expansion and combination stages of the phase 1 study will be based on investigator-assessed, immune-related response criteria(irRC) and independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.
About ALKS 4230
ALKS 4230 is a novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while overcoming its limitations.
About
Note Regarding Forward-Looking Statements
Certain statements set forth in this press release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the potential therapeutic and commercial value of ALKS 4230; and clinical development plans for ALKS 4230, including the timing of the expected presentation of, and other details concerning, the initial data from the monotherapy dose-escalation stage of the phase 1 study, and the expected timing and details of the planned monotherapy dose-expansion stage of the phase 1 study, the newly initiated combination therapy stage of the phase 1 study and the planned subcutaneous dosing study. You are cautioned that forward-looking statements are inherently uncertain. Although the company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond the company's control, which could cause actual results to differ materially from those expressed or implied in the forward-looking statements. These risks and uncertainties include, among others, whether preclinical and early clinical results for ALKS 4230 will be predictive of future clinical study results; whether ALKS 4230 could be shown to be unsafe or ineffective; whether future clinical trials or future stages of ongoing clinical trials for ALKS 4230 will be initiated or completed on time or at all; changes in the cost, scope and duration of development activities for ALKS 4230; and those risks and uncertainties described under the heading "Risk Factors" in the company's Annual Report on Form 10-K for the year ended
KEYTRUDA® is a registered trademark of
Alkermes Contacts: |
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For Investors: |
Eva Stroynowski, +1 781 609 6823 |
Sandy Coombs, +1 781 609 6377 |
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For Media: |
Sherry Feldberg, +1 781 609 6276 |
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