Phase 3 Trial Shows Combined Nivolumab, Ipilimumab Treatment Improved OS in Patients With mNSCLC

Recent results from the 6-year duration part 1 of the phase 3 CheckMate 227 trial (NCT02477826) had met both primary endpoints. CheckMate 227 continues to demonstrate long-term, durable survival benefits of the combined nivolumab (Opdivo; Bristol Myers Squibb) and ipilimumab (Yervoy; Bristol Myers Squibb) treatment compared to chemotherapy in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC), regardless of PD-L1 expression levels.¹

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CheckMate is a multi-part, open-label, randomized, global phase 3 trial evaluating nivolumab-based regimens compared to platinum-doublet chemotherapy in patients with first-line mNSCLC across non-squamous and squamous tumor histologies. Enrolled patients with tumor PD-L1 ≥1% were randomized to receive treatment with nivolumab plus ipilimumab, nivolumab alone, or chemotherapy alone, and patients with tumor PD-L1 <1% were randomized to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. Patients were assessed at follow-up after a minimum of 6 years (73.5 months) to assess overall survival (OS) in those with tumors that expressed PD-L1, and progression-free survival (PFS) in those with tumor mutation burden of 10 or greater mutations/megabase across the PD-L1 spectrum.^1,2

“Immunotherapy has transformed the treatment of advanced lung cancer, and thankfully, a diagnosis no longer means the same thing as it used to for many patients. With these 6-year results, we are seeing remarkably sustained and durable clinical survival benefits with nivolumab plus ipilimumab year-over-year,” said Solange Peters, MD, PhD, professor and chair of medical oncology and the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland, in a press release. “The long-term efficacy seen with the dual immunotherapy regimen in CheckMate227 reinforce the importance of nivolumab plus ipilimumab to transform outcomes for appropriate patients with metastatic NSCLC.”¹

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to utilize the body’s immune system to help restore its response to tumors. It has become an important treatment option across various types of cancers and was the first PD-1 immune checkpoint inhibitor to receive regulatory approval.¹

In March 2011, the FDA approved the 3mg/kg dose of ipilimumab for monotherapy for patients with unresectable or metastatic melanoma. Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity, and ipilimumab binds to it, blocking the interaction of CTLA-4 with its ligands CD80/CD86. A blockade of CTLA-4 has been shown to augment T-cell activation and growth, which includes tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which can potentially lead to a general increase in T-cell responsiveness, including the anti-tumor response.¹

At a 73.5-month minimum follow-up, the combination of nivolumab and ipilimumab continued to present OS benefits in patients with tumor PD-L1 of 1% greater or less than 1% compared to chemotherapy alone, with OS rates being 22% vs 13% and 16% vs 5%, respectively. Consistent clinical benefit was observed across additional efficacy endpoints in all patients regardless of the tumor PD-L1 expression. Further, larger proportions of responders had presented tumor burden reduction of 80% or greater with the combined treatment of nivolumab and ipilimumab compared to chemotherapy alone. Further, 6-year OS rates were respectively higher (59% vs 42%; 77% vs 0%) regardless of the treatment received; for patients who had completed the EQ-5D-3L visual analog scale assessments with 5 years (61.3 months) minimum follow-up, median OS was longer in those with high versus low baseline scores (nivolumab + ipilimumab, 19.7 [16.7-23.9] vs 14.9 [12.2-18.1] months; chemotherapy, 17.8 [15.0-19.8] vs 10.1 [7.8-12.2] months).^1,2

“We are ecstatic to see [nivolumab] plus [ipilimumab] continue to demonstrate almost double the OS rates as chemotherapy after 6 years of follow-up—the longest-ever for a phase 3 trial with immunotherapy in mNSCLC. Further, the [nivolumab] plus [ipilimumab] regimen more than tripled survival for patients with PD-L1 expression [at less than] 1%, a population that is difficult to treat and faces high unmet needs,” Abderrahim Oukessou, MD, vice president of Bristol Myers Squibb’s thoracic cancers global program lead, said in the press release.¹

The 6-year update represents the longest follow-up across immunotherapy trials in mNSCLC. In patients with tumor PD-L1 at 1% greater or less than <1%, the combined nivolumab and ipilimumab treatment continued to demonstrate long-term, durable efficacy benefit compared to chemotherapy. Additionally, patients with higher tumor burden reduction had greater long-term OS when receiving the combined nivolumab and ipilimumab treatment.²

“Looking ahead, we are excited to expand our research into targeted and small molecule therapies, as well as additional immunotherapy combinations, in the hope of potentially finding solutions for as many people living with thoracic cancers as possible,” Oukessou said in the press release.¹

References

1. Bristol Myers Squibb. Six-Year Outcomes from Phase 3 CheckMate -227 Trial Show Durable, Long-Term Survival with Opdivo (nivolumab) Plus Yervoy (ipilimumab) in the First-Line treatment of Patients with Metastatic Non-Small Cell Lung Cancer. News release. September 11, 2023. Accessed September 11, 2023. https://bit.ly/3ECz4Ad

2. Six-year Survival and HRQoL Outcomes with 1L Nivolumab + Ipilimumab in Patients with Metastatic NSCLC from CheckMate227. Abstract #OA14.03. Presented at: World Conference on Lung Cancer; Singapore. Accessed September 11, 2023. https://cattendee.abstractsonline.com/meeting/10925/Session/106