Treatment of cancer by combination of immune checkpoint inhibitor and folfirinox therapy

Inventors

Kimura, Keisuke • Kuroda, Masataka • IWATA, Takeyuki

Assignees

Ono Pharmaceutical Co Ltd

Abstract

A new therapeutic method in which a combination of an immune checkpoint inhibitor and a FOLFIRINOX therapy, a modified FOLFIRINOX therapy or a dose-reducing regimen of each of the therapies is effective to treat cancer, particularly cancer difficult to treat with conventional therapies such as pancreatic cancer.

Core Innovation

The invention provides a method for suppressing the progression of, suppressing the recurrence of and/or treating pancreatic cancer or biliary tract cancer by administering nivolumab as an active ingredient in combination with FOLFIRINOX therapy or a dose-reducing regimen thereof. The method uses nivolumab together with FOLFIRINOX rather than as a preoperative therapy.

The method defines that the administration of nivolumab does not include administration as a preoperative therapy, where the preoperative therapy is a preceding therapy with an anti-cancer drug prior to cancer resection surgery performed for preventing postoperative micrometastases of invasive cancer and preventing recurrence thereof. The combination therefore positions nivolumab in a non-preoperative context while pairing it with FOLFIRINOX therapy for pancreatic cancer and biliary tract cancer.

In the claimed treatment, nivolumab is administered at about 3 mg/kg body weight per dose or at about 240, 360, or 480 mg per dose every 2 to 4 weeks, and the FOLFIRINOX therapy comprises oxaliplatin (L-OHP), irinotecan hydrochloride hydrate (CPT-11), levofolinate calcium (I-LV), and fluorouracil (5-FU). For the dose-reducing regimen, a dose of any of L-OHP, CPT-11, I-LV, or 5-FU is reduced from the initial administration or during second and subsequent cycles of the FOLFIRINOX therapy.

For certain embodiments, the method further coordinates nivolumab and FOLFIRINOX on the same day, with nivolumab administered first and the start of the FOLFIRINOX therapy at least about 30 minutes after completion of nivolumab administration. For specific subject and disease contexts, including distant metastatic pancreatic cancer and subjects without prior anti-cancer drugs, the method specifies a particular nivolumab dosing pattern and a reduced FOLFIRINOX administration series repeated every 2 weeks.

Claims Coverage

The partial content includes two independent claims. Both claims focus on combination therapy with nivolumab and FOLFIRINOX or a dose-reducing regimen, with constraints excluding preoperative nivolumab, specifying dose and interval features for nivolumab, and defining dose-reducing aspects of FOLFIRINOX; the second independent claim also fixes a specific distant metastatic pancreatic cancer dosing schedule and an eligible-subject condition.

Across the two independent claims, the coverage centers on combination methods using nivolumab with FOLFIRINOX, including a dose-reducing regimen. Inventive features include excluding nivolumab as preoperative therapy, specifying nivolumab dose and interval options, defining dose reduction within the FOLFIRINOX cycles, and, in the second independent claim, using a fixed distant metastatic pancreatic cancer dosing scheme with reduced FOLFIRINOX repeated every 2 weeks for subjects without prior anti-cancer drugs.

Stated Advantages

Documented Applications

No documented applications found