Ono Pharmaceutical Co., Ltd....and Bristol-Myers Squibb...announced today that ONO received approval of Opdivo® (generic name: nivolumab) Intravenous Infusion (“Opdivo”), a human anti-human programmed cell death-1 (PD-1) monoclonal antibody in Japan for the following two additional indications, for a partial change in approved items of the manufacturing and marketing approval:...Microsatellite instability high (MSI-High) unresectable advanced or recurrent colorectal cancer that has progressed following chemotherapy...

OPDIVO is a programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of...adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in combination with ipilimumab.

...the panel recommends pembrolizumab or nivolumab, alone or in combination with ipilimumab, as options for first-line treatment of MSI-H/dMMR mCRC only for patients who are not appropriate for intensive therapy.

...Objective response rate (ORR) in all MSI-High and non-MSI-High subjects as determined by Investigators...

Nivolumab provided durable responses and disease control in pre-treated patients with dMMR/MSI-H metastatic colorectal cancer...

The 48-mo PFS rates were 36%, 54%, and 51% and 48-mo OS rates were 49%, 71%, and 72% in C1, C2, and C3, respectively...With extended follow-up of ~5 years, NIVO ± IPI continued to demonstrate durable OS and PFS benefit...These updated data further support current treatment recommendations for 2L+ NIVO ± IPI and 1L NIVO + IPI for pts with MSI-H/dMMR mCRC.

Subgroup analyses were conducted according to the categories of dMMR-MSI-H (tumors with mismatch repair deficiency and high levels of microsatellite instability) ≥ 5% vs. dMMR-MSI-H < 5%, monotherapy vs. combination therapy, PD-1 inhibitors vs. PD-L1 inhibitors, and nivolumab vs. pembrolizumab. The ORRs of the dMMR-MSI-H ≥ 5% and dMMR-MSI-H < 5% subgroups were 0.40 (95% CI 0.30-0.51) and 0.04 (95% CI 0.00-0.09), respectively. PD-1/PD-L1 inhibitors produced encouraging clinical benefits including the response rate in the treatment of dMMR-MSI-H mCRC.

Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%.