Today three-year follow-up results from Part 1 of the Phase 3 CheckMate -227 trial have been announced, demonstrating that nivolumab plus ipilimumab provided sustained improvements in overall survival and additional efficacy measures as a first-line treatment for patients with metastatic non-small cell lung cancer.

With a median follow-up of more than three years (43.1 months), nivolumab plus ipilimumab continued to show a survival benefit compared to chemotherapy [Hazard Ratio (HR): 0.79; 95% Confidence Interval (CI): 0.67 to 0.93] among patients whose tumours expressed PD-L1 ≥1%.

Three-year OS rates in this population were 33% for nivolumab plus ipilimumab, compared to 22% for chemotherapy alone.

Nivolumab plus ipilimumab also delayed disease progression or death among these patients, with a three-year progression-free survival (PFS) rate of 18% with the combination versus 4% with chemotherapy alone.

Thirty-eight percent of patients with PD-L1 ≥1% who responded to nivolumab plus ipilimumab remained in response three years after the onset of the response versus 4% for chemotherapy alone.

These ongoing responses were observed in the absence of treatment with nivolumab plus ipilimumab, which were given for a maximum of two years per the trial protocol. In an exploratory landmark analysis of OS by response status, 70% of patients whose tumours expressed PD-L1 ≥1% and who had a complete or partial response by six months to the nivolumab plus ipilimumab combination were alive three years later, compared to 39% of patients treated with chemotherapy.

In an exploratory analysis of patients whose tumours expressed PD-L1 <1%, nivolumab plus ipilimumab demonstrated three-year OS rates of 34%, compared to 15% for chemotherapy alone (HR: 0.64; 95% CI: 0.51 to 0.81).

Additionally, 13% versus 2% of patients remained alive and progression-free from time of randomization; and 34% versus 0% of patients with confirmed responses to treatment remained in response three years after the onset of the response, respectively.

The safety profile of nivolumab plus ipilimumab was consistent with previously reported studies in NSCLC, and no new safety signals were observed.

These results will be featured in an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting 2020, held virtually, from May 29-31.

“Non-small cell lung cancer is a complex and aggressive disease, and despite recent treatment advances, patients remain in need of additional options that may provide a long-lasting survival benefit,” said Suresh S. Ramalingam, M.D., CheckMate -227 study investigator, Deputy Director, Winship Cancer Institute of Emory University, Assistant Dean for Cancer Research, Emory School of Medicine.

“The three-year outcomes from CheckMate -227 show evidence of sustained survival gains with nivolumab plus ipilimumab in the first-line treatment of non-small cell lung cancer; the data reaffirm the established scientific rationale that dual inhibition of PD-1 and CTLA-4 has the potential to deliver deep and durable responses for certain patients.”

The addition of ipilimumab to nivolumab also continued to show benefit compared to nivolumab monotherapy in patients whose tumours expressed PD-L1 ≥1% and compared to nivolumab plus chemotherapy in those with PD-L1 <1% with a minimum of three years of follow-up.

“We now have long-term overall survival results for nivolumab plus ipilimumab in Phase 3 trials across three tumour types – advanced non-small cell lung cancer, melanoma and renal cell carcinoma – as well as positive data from a pivotal trial in first-line mesothelioma and a second trial in first-line non-small cell lung cancer,” said Nick Botwood, M.D., vice president, Oncology Clinical Development, Bristol Myers Squibb.

“In addition, having met the primary endpoint of overall survival in PD-L1 expressers, we look forward to a potential U.S. Food and Drug Administration approval of nivolumab plus ipilimumab in first-line non-small cell lung cancer, which would mark the fifth indication for the combination. Taken in this context, the three-year data from CheckMate -227 Part 1 contribute to a growing body of evidence around the durable benefits with our dual immunotherapy approach.”

nivolumab plus ipilimumab is a unique combination of two immune checkpoint inhibitors that features a potentially synergistic mechanism of action, targeting two different checkpoints (PD-1 and CTLA-4) to help destroy tumour cells: ipilimumab helps activate and proliferate T cells, while nivolumab helps existing T cells discover the tumour.

Some of the T cells stimulated by ipilimumab can become memory T cells, which may allow for a long-term immune response.

About CheckMate -227

CheckMate -227 is a multi-part open-label Phase 3 trial evaluating nivolumab-based regimens versus platinum-doublet chemotherapy in patients with first-line advanced non-small cell lung cancer across non-squamous and squamous tumour histologies.

There are two co-primary endpoints in Part 1 for nivolumab plus ipilimumab (versus chemotherapy): overall survival (OS) in patients whose tumours express PD-L1 (assessed in patients enrolled in Part 1a) and progression-free survival (PFS) in patients with tumour mutational burden (TMB) ≥10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b).

Patients were dosed as follows:

• - Part 1a: nivolumab (3 mg/kg every 2 weeks) plus low-dose ipilimumab (1 mg/kg every 6 weeks) or nivolumab monotherapy (240 mg every 2 weeks) versus chemotherapy (every 3 weeks for up to four cycles) in patients whose tumours express PD-L1 (≥1%)

• - Part 1b: nivolumab plus low-dose ipilimumab or nivolumab (360 mg every 3 weeks) plus chemotherapy (every 3 weeks for up to four cycles) versus chemotherapy (every 3 weeks for up to four cycles) in patients whose tumours do not express PD-L1 (<1%)

Part 1 met both its co-primary endpoints of PFS with the nivolumab plus ipilimumab combination versus chemotherapy in patients whose tumours have high (≥10 mutations/megabase, mut/mb) TMB, regardless of PD-L1 expression, and OS demonstrating a superior benefit for nivolumab plus low-dose ipilimumab versus chemotherapy in first-line NSCLC patients whose tumours expressed PD-L1 ≥1%.

Source: Bristol Myers Squibb