Immunomodulatory IL-2 agents in combination with immune checkpoint inhibitors
Inventors
LOSEY, HEATHER C. • Lopes, Jared • Winquist, Raymond J.
Assignees
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Publication Number
US-11945870-B2
Publication Date
2024-04-02
Expiration Date
Abstract
The invention provides compositions and methods of treating cancer in a patient with a combination therapy comprising a fusion protein of SEQ ID NO: 1 in combination with an immune checkpoint inhibitor. Preferably the patient has failed to achieve complete or partial response with prior or ongoing treatment with an immune checkpoint inhibitor.
Core Innovation
The patent describes an anti-cancer combination therapy for a patient in need thereof that includes a fusion protein of SEQ ID NO: 1, or a variant thereof, together with an immune checkpoint inhibitor. The fusion protein is administered in a therapeutically effective amount in relation to the immune checkpoint inhibitor, with step (i) carried out before, after or simultaneously with step (ii). Variant fusion proteins are constrained to be at least 80% identical to full length SEQ ID NO: 1.
The fusion protein and immune checkpoint inhibitor combination is framed as a strategy to selectively target intermediate-affinity IL-2 receptor IL-2Rβγ while expanding CD8+ and NK cells and minimizing Treg activation. The patent emphasizes use in patients who failed to achieve complete/partial response to prior or ongoing checkpoint therapy, using RECIST and irRECIST response assessments. The immune checkpoint inhibitor is described in the context of PD-1/PD-L1 and CTLA-4.
The disclosed rationale and study context include clinical and preclinical components and correlative biomarker assessment, including tumor biopsies, tumor microenvironment and immunohistochemistry, sequencing and immune phenotyping. Clinical outcome reporting and ongoing trial context are summarized, including ARTISTRY-1 ovarian cancer results and ARTISTRY-2 subcutaneous study context. Preclinical mouse model results are described as enhanced tumor growth inhibition and increased complete responses for combination therapy versus monotherapies, with tumor models including MC38 and B16F10.
Claims Coverage
The document identifies one independent claim describing combination treatment of cancer using a fusion protein of SEQ ID NO: 1 (or a variant) together with an immune checkpoint inhibitor, where the two steps can be given in any order and the fusion protein variant identity is constrained. The independent claim contains two core inventive constraints: the timing relationship between the two administered therapeutic components, and the sequence identity threshold for allowable fusion-protein variants.
Combination therapy with fusion protein and immune checkpoint inhibitor
A method of treating cancer in a patient in need thereof comprising administering a therapeutically effective amount of a fusion protein of SEQ ID NO: 1, or a variant thereof, and administering a therapeutically effective amount of an immune checkpoint inhibitor.
Order-independent administration of the two therapeutic steps
The method wherein step (i) is carried out before, after or simultaneously with step (ii).
Variant identity threshold for the fusion protein
The method wherein the variant fusion protein is at least 80% identical to full length SEQ ID NO: 1.
Overall, claim coverage centers on administering a therapeutically effective amount of a SEQ ID NO: 1 fusion protein (or an at-least-80%-identical variant) together with a therapeutically effective amount of an immune checkpoint inhibitor, with administration occurring before, after, or simultaneously.
Stated Advantages
Increased DOR, PFS, TTP, and OS compared with patients receiving the fusion protein of SEQ ID NO: 1 or an immune checkpoint inhibitor given as monotherapy.
Documented Applications
Anti-cancer treatment in a patient in need thereof, including use in patients who failed to achieve complete/partial response to prior or ongoing checkpoint therapy (RECIST/irRECIST).
Combination evaluation in ovarian cancer (ARTISTRY-1) and a subcutaneous fusion protein study context (ARTISTRY-2).
Preclinical evaluation in mouse tumor models including MC38 and B16F10, with combination therapy showing enhanced tumor growth inhibition and increased complete responses versus monotherapies.
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