EU Approval Recommended for Opdivo-Yervoy-Chemo Combo for Advanced NSCLC

EU Approval Recommended for Opdivo-Yervoy-Chemo Combo for Advanced NSCLC

European Medicines Agency (EMA) committee has recommended that a combination therapy of Opdivo (nivolumab) and Yervoy (ipilimumab) plus two cycles of platinum-based chemotherapy be approved in the European Union (EU) as first-line treatment for advanced non-small cell lung cancer (NSCLC).

The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended the approval specifically for adults whose tumors contain no mutations in the EGFR or ALK genes.

Opinions released by the CHMP are generally accepted by the European Commission (EC), which makes the final decisions on approving all treatments used in the EU.

“This positive CHMP opinion reflects the potential for Opdivo plus Yervoy with two cycles of chemotherapy to offer the chance for a longer life to patients across subgroups of metastatic NSCLC, a devastating cancer where unmet needs still exist,” said Abderrahim Oukessou, MD, vice president and development team leader of thoracic cancers at Bristol Myers Squibb, said in a press release.

Bristol Myers Squibb is the developer of both Opdivo and Yervoy.

“We look forward to the EC’s decision and hope to soon introduce this innovative, dual immunotherapy approach to patients across the EU who may benefit,” Oukessou added.

If approved, Europe will follow nine other countries, including the U.S. and Canada, in authorizing the triple combo as a treatment for the same indication. It also would mark the third indication for Opdivo plus Yervoy­-based combinations in the EU, following previous approvals for advanced melanoma and certain types of kidney cancer.

Opdivo and Yervoy are two immune checkpoint inhibitors that work by blocking mechanisms used by cancer cells to evade immune system attack. Opdivo targets the PD-1 protein on cancer cells while Yervoy targets the CTLA-4 protein on T-cells, which are immune cells involved in the fight against cancer.

The CHMP’s positive opinion was based on data from the ongoing, global, open-label, CheckMate-9LA Phase 3 clinical trial (NCT03215706).

That study is evaluating whether initial treatment with the triple combo is more effective than conventional chemotherapy in 719 adults with untreated advanced NSCLC, which is either metastatic (spread to different parts of the body) or recurrent. The results were found to occur regardless of tumor PD-L1 levels or histology (squamous or non-squamous).

The amount of PD-L1, the PD-1 ligand present on the surface of T-cells, is often seen as a predictor of responses to PD-1/PD-L1-targeting agents like Opdivo.

Participants were randomly assigned to receive either intravenous (into-the-vein) injections of Opdivo, Yervoy, and two cycles of platinum-based chemotherapy (361 patients), or up to four cycles of chemotherapy, followed by optional maintenance therapy with pemetrexed (358 patients). Opdivo was given through 360 mg doses every three weeks and Yervoy at 1 mg/kg every six weeks.

Treatment with the triple combo continued for up to two years, or until disease progression or unacceptable toxicity.

The trial’s main goal was to assess whether the triple combo was superior to standard chemotherapy at prolonging patients’ overall survival. Secondary goals included the time patients lived without disease progression, the proportion of participants responding to treatment, and survival outcomes in individuals with different tumor PD-L1 levels.

The full data, presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, showed that the trial met both its main and key secondary goals.

At one year, 63% of patients given the combination therapy were alive, compared with 47% of those treated with chemotherapy alone. After a minimum follow-up of 12.7 months, participants on the triple combo lived significantly longer (15.6 months) than those given standard chemotherapy (10.9 months), representing a 34% reduction in their risk of death.

The time patients lived without disease worsening and responses to treatment also were significantly better with the triple combo. All clinical benefits were consistent across different patient subgroups, with the results independent of PD-L1 levels and histology.

The safety profile of the combination therapy also was consistent with the known profiles of each therapy in people with untreated NSCLC. Severe to life-threatening adverse events were reported in 47% of patients receiving the triple combo, compared with 38% of those on chemotherapy alone.

In the release, Bristol Myers Squibb thanked the patients and investigators who were involved in the CheckMate-9LA study.