Nivolumab Monotherapy Shows Efficacy for Disease Control in Rare Tumors

A new study showed that nivolumab was effective in patients with pathogenic exonuclease domain POLE mutated mismatch repair.

Nivolumab monotherapy showed high response and disease control rates in pathogenic exonuclease domain POLE (edPOLE) mutated mismatch repair (MMR)-proficient advanced tumors containing confirmed pathogenic mutations, according to new findings presented at the European Society for Medical Oncology Virtual Congress 2020.

The study noted that edPOLE hotspots are caused by mutations generating proofread defects and hypermutated genomic profiles that may be good targets for existing therapies. These hotspots rarely occur in advanced disease and have not been fully investigated, meaning the efficacy of nivolumab in MMR-proficient tumors and edPOLE has not been established.

The study, which took place between January 2018 and April 2020, enrolled 16 participants with a mean age of 57 years. Additionally, the participants had a mean of 2.6 lines of prior therapy. Of these patients, 7 had colorectal cancer, 4 had endometrial cancer, 2 had gastric cancer, and 1 patient had pancreatic, biliary, and glial tumors.

All participants in the cohort received 240 mg of nivolumab intravenously and continued until disease progression, toxicity, or up to 2 years in their absence. The primary endpoint was the objective response rate (ORR) assessed per RECIST v1.1 at 12 weeks, according to the study.

At 12 weeks, the ORR was 38%, which included 5 partial responses and 6 stable disease. Five of the 16 patients experienced progressive disease at this time. Responses were observed exclusively in patients with MMR-proficient colorectal and endometrial cancers. The median follow-up was 7.0 months, with a minimum of 1 month and a maximum of 21.9 months.

In a group of 8 patients with pathogenic mutations, the ORR was 50%. Stable disease was achieved by 2 of the 8 patients with a disease control rate of 75%. Two of the 3 patients with unknown significance mutations had responses and 1 had stable disease. At 12 weeks, all 5 of the patients with non-pathogenic tumors experienced disease progression, including 2 who had died prior to the first evaluation.

According to the study, this was the first clinical study to assess an anti-programmed cell death protein 1 agent in POLE mutated MMR-proficient tumors. They researchers determined that activity from treatment with nivolumab shows promiss in patients with edPOLE mutated MMR-proficient advanced cancer, but the effect may be limited to tumors containing pathogenic mutations.

The safety profile of nivolumab was in accordance with safety data reported in other tumor types. Investigators emphasized that these results underscore the importance of individual mutational functional assessments by a molecular tumor board.

Reference:

NIVOLUMAB SHOWS PROMISING ACTIVITY IN ADVANCED TUMOURS WITH RARE MUTATIONS [News Release] September 20, 2020; New York, NY. ESMO https://www.esmo.org/meetings/esmo-virtual-congress-2020/meeting-resources/scientific-news/nivolumab-shows-promising-activity-in-advanced-tumours-with-rare-mutations. Accessed September 23, 2020.