The European Medicines Agency has agreed to review Bristol Myers Squibb’s application requesting approval for the dual immunotherapy regimen Opdivo (nivolumab) and Yervoy (ipilimumab) for untreated, inoperable malignant pleural mesothelioma (MPM).
This decision comes after promising data from the Phase 3 CheckMate-743 trial (NCT02899299), in which the immunotherapy combo prolonged patients’ lives from a median of 14.1 months with standard chemo to 18.1 months.
“We look forward to working with urgency alongside the EMA towards the goal of bringing this dual immunotherapy combination to patients in Europe, which faces one of the highest incidences of mesothelioma in the world,” Sabine Maier, MD, vice president of oncology clinical development at Bristol Myers Squibb, said in a press release.
Opdivo and Yervoy are two immune checkpoint inhibitors developed by the company. They boost immune responses against cancer cells by blocking the activity of two proteins — PD-1 in the case of Opdivo and CTLA-4 in the case of Yervoy — found on the surface of immune T-cells.
Cancer cells often hijack these proteins to avoid destruction by the immune system. By blocking their activity, the medications are expected to increase T-cell numbers and their effectiveness at recognizing and eliminating malignant cancer cells.
When used together, their effects are thought to be amplified, as Yervoy can promote the activation and formation of new T-cells, including memory T-cells, while Opdivo can help existing T-cells find the tumor.
CheckMate-743 is investigating the safety and effectiveness of this combination as a first-line therapy in people with newly diagnosed, inoperable MPM, a cancer affecting the protective lining surrounding the lungs.
A total of 605 participants were randomly assigned to the Opdivo-Yervoy combination (303 patients) or to standard treatment with one of two platinum-based chemotherapy regimens: cisplatin or carboplatin plus pemetrexed.
Those in the immunotherapy arm received both medications for up to two years, or until they showed signs of disease progression or unacceptable toxicity. Chemotherapy was given for up to six cycles, or until disease progression or unacceptable toxicity.
The primary goal of this trial was to determine whether the immunotherapy combination was superior to chemotherapy at prolonging patient survival.
After a minimum follow-up of 22 months, results showed that patients on the Opdivo-Yervoy combo lived a median of 18.1 months, while the median overall survival for those receiving chemotherapy was 14.1 months. This corresponded to a 26% lower risk of death.
Two years after starting treatment, nearly half (41%) of the patients treated with the immunotherapies were still alive, compared with 27% of those receiving standard treatment.
The survival benefits were seen across different mesothelioma subtypes, including those with the non-epithelioid form that is normally associated with a poorer prognosis. In this subset of patients, the combination prolonged survival from a median of 8.8 to 18.1 months.
“Not only is malignant pleural mesothelioma a particularly aggressive cancer, it has also proven difficult to treat, with no new options approved in years that can meaningfully extend survival,” Maier said. “The CheckMate-743 trial has shown the potential for Opdivo plus Yervoy to help address this significant unmet need.”