Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer
Inventors
Martini, Jean-Francois Andre • Tarazi, Jamal Christo • Perini, Rodolfo Fleury • Mauro, David J.
Assignees
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Publication Number
US-12534530-B2
Publication Date
2026-01-27
Expiration Date
Abstract
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a VEGFR inhibitor, and the use of the combination therapies for the treatment of cancer, and in particular for treating cancers that express PD-L1.
Core Innovation
The patent describes treating cancer by combining a PD-1 blockade with inhibition of the VEGF receptor pathway. The PD-1 blockade preferably inhibits binding of PD-L1 to PD-1, and optionally binding of PD-L2 to PD-1, thereby providing a PD-1/PD-L1 blockade in combination with VEGFR-pathway inhibition. The disclosure focuses on PD-L1/PD-L2-expressing tumors as a context for the combination therapy.
The patent identifies PD-1 antagonists, including anti-PD-1 monoclonal antibodies such as pembrolizumab (MK-3475) and nivolumab, and discusses embodiments in terms of monoclonal antibody structure including heavy chain and light chain CDRs with specified SEQ ID NOs. It further identifies VEGFR inhibitors, including axitinib (AG-013736), as preferred agents for the VEGFR-pathway inhibition component of the combination.
In the renal cell carcinoma setting, the patent includes embodiments for a method of treating renal cell carcinoma in an individual who has not been previously treated for RCC using a combination therapy comprising pembrolizumab and axitinib. The embodiments also describe use in treatment-naive advanced clear-cell kidney cancer with resected primary tumor and elevated or positive PD-L1 expression.
Claims Coverage
The partial content provides two independent claims: one covering axitinib dose escalation based on tolerability, and the other covering axitinib dose reduction based on tolerability of the dose combination. Together, they cover administering combination therapy of pembrolizumab and axitinib in previously untreated RCC individuals, with axitinib starting at 5 mg BID and dose modification in response to tolerability.
Pembrolizumab plus axitinib for previously untreated RCC with dose escalation by tolerability
Administering a combination therapy comprising pembrolizumab and axitinib to treat renal cell carcinoma in an individual who has not been previously treated for RCC, wherein axitinib is administered at a starting dose of 5 mg twice daily and is then increased to a maximum dose of 10 mg twice daily if the individual tolerates axitinib with no drug-related grade >2 adverse events for two consecutive weeks.
Pembrolizumab plus axitinib for previously untreated RCC with dose reduction by tolerability
Administering a combination therapy comprising pembrolizumab and axitinib to treat renal cell carcinoma in an individual who has not been previously treated for RCC, wherein axitinib is administered at a starting dose of 5 mg twice daily and, if the dose combination is not tolerated by the individual, the dose of axitinib is reduced to a minimum dose of 3 mg twice daily.
Across the independent claims, the core inventive coverage is combination therapy using pembrolizumab together with axitinib for treating previously untreated RCC individuals, with axitinib starting at 5 mg BID and then either increased to 10 mg BID if tolerability criteria are met or reduced to 3 mg BID if the combination is not tolerated.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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