Treatment of tumors with an anti-CSF-1R antibody in combination with an anti-PD-L1 antibody after failure of anti-PD-L1/PD1 treatment
Inventors
Cannarile, Michael • JEGG, Anna-Maria • MICHIELIN, Francesca • Ries, Carola • Ruettinger, Dominik • WEISSER, MARTIN
Assignees
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Publication Number
US-11498968-B2
Publication Date
2022-11-15
Expiration Date
Abstract
The current invention relates to the combination therapy of an anti-CSF-1R antibody (especially a CSF-1R dimerization inhibitor) in combination with an anti-PD-L1 antibody after PD1/PD-L1 inhibitor treatment failure, corresponding pharmaceutical compositions or medicaments using such combination therapy.
Core Innovation
A method of treating cancer in a human patient is provided by administering, after or in relation to failure of a programmed death ligand 1/programmed cell death protein 1 (PD-L1/PD1) inhibitor, a combination of a therapeutically effective amount of an anti-colony stimulating factor 1 receptor (CSF-1R) antibody and a therapeutically effective amount of an anti-programmed death ligand 1 (PD-L1) antibody. The patient is previously treated with a PD-L1/PD1 inhibitor selected from atezolizumab, pembrolizumab, and nivolumab and the prior treatment fails according to response evaluation criteria in solid tumors (RECIST) 1.1 criteria.
The method is directed to cancer where the cancer is urinary bladder cancer (UCB) or non-small cell lung (NSCL) cancer and the cancer comprises tumor cells and infiltrating CSF-1R-expressing M2-like tumor-associated macrophages. The anti-CSF-1R antibody and the anti-PD-L1 antibody are monoclonal antibodies comprising a constant region capable of activating antibody-dependent cell-mediated cytotoxicity.
The combination specifies antibody feature constraints for the anti-CSF-1R antibody and the anti-PD-L1 antibody by including particular variable domain sequences. The anti-CSF-1R antibody comprises a heavy chain variable domain VH of SEQ ID NO:1 and a light chain variable domain VL of SEQ ID NO:2, and the anti-PD-L1 antibody comprises a heavy chain variable domain VH of SEQ ID NO:3 and a light chain variable domain VL of SEQ ID NO:4.
Claims Coverage
The independent claim provides a treatment method defined by a specific two-antibody combination targeting CSF-1R and PD-L1, a defined patient history of PD-L1/PD1 inhibitor failure by RECIST 1.1, specific cancer types (UCB or NSCL) with infiltrating CSF-1R-expressing M2-like tumor-associated macrophages, and monoclonal antibodies with Fc effector function plus specified VH/VL sequence identifiers. Only one independent claim is present in the provided claim set.
Combination of anti-CSF-1R and anti-PD-L1 after PD-L1/PD1 failure by RECIST 1.1
A method of treating cancer comprising administering to a human patient a therapeutically effective amount of an anti-CSF-1R antibody in combination with a therapeutically effective amount of an anti-PD-L1 antibody, wherein the patient was previously treated with a PD-L1/PD1 inhibitor selected from atezolizumab, pembrolizumab, and nivolumab and the prior treatment failed according to RECIST 1.1 criteria.
Defined cancer context with CSF-1R-expressing M2-like tumor-associated macrophages
The cancer is urinary bladder cancer (UCB) or non-small cell lung (NSCL) cancer, and comprises tumor cells and infiltrating CSF-1R-expressing M2-like tumor-associated macrophages.
Monoclonal antibodies with Fc region capable of activating ADCC
Both the anti-CSF-1R antibody and the anti-PD-L1 antibody are monoclonal antibodies that comprise a constant region capable of activating antibody-dependent cell-mediated cytotoxicity.
Specified variable domain identities for both antibodies
The anti-CSF-1R antibody comprises a heavy chain variable domain VH of SEQ ID NO:1 and a light chain variable domain VL of SEQ ID NO:2, and the anti-PD-L1 antibody comprises a heavy chain variable domain VH of SEQ ID NO:3 and a light chain variable domain VL of SEQ ID NO:4.
Across the independent claim, the inventive scope is centered on post–PD-L1/PD1 inhibitor failure treatment (RECIST 1.1) using a monoclonal anti-CSF-1R plus monoclonal anti-PD-L1 combination for UCB or NSCL cancers characterized by tumor cells with infiltrating CSF-1R-expressing M2-like tumor-associated macrophages, with Fc-mediated antibody-dependent cell-mediated cytotoxicity and specified VH/VL sequence identifiers.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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