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MAY 13, 2020: Bristol Myers Squibb announced the first presentation of results from the Phase 3 CheckMate -9LA trial, which demonstrated a statistically significant and clinically meaningful survival benefit with Opdivo (nivolumab)plus Yervoy (ipilimumab), given concomitantly with two cycles of chemotherapy, for the first-line treatment of metastatic non-small cell lung cancer (NSCLC).
The study met both its primary and key secondary endpoints, demonstrating superior overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) for the dual immunotherapy plus chemotherapy combination versus chemotherapy alone.
At a prespecified interim analysis for the primary endpoint of OS, Opdivo plus Yervoy combined with two cycles of chemotherapy reduced the risk of death by 31% compared to chemotherapy alone at a minimum follow-up of 8.1 months [Hazard Ratio (HR): 0.69, 96.71% Confidence Interval (CI): 0.55 to 0.87; p=0.0006].
Additionally, with longer follow-up (minimum of 12.7 months), the combinationcontinued to show sustained OS improvements over chemotherapy alone (median OS of 15.6 months versus 10.9 months, respectively [HR: 0.66, 95% CI: 0.55 to 0.80]).
The clinical benefit was observed across all efficacy measures in key population subgroups, including by PD-L1 expression and tumor histology (squamous or non-squamous).
The safety profile of Opdivo (360 mg every three weeks) plus Yervoy (1 mg/kg every six weeks) and two cycles of chemotherapy was reflective of the known safety profiles of the immunotherapy and chemotherapy components in first-line NSCLC.
These results (Abstract #9501) will be featured in an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting 2020, held virtually, from May 29-31.
“The nivolumab plus ipilimumab combination has been shown to increase survival in patients with first-line non-small cell lung cancer, and adding a limited course of chemotherapy may help mitigate the risk of early disease progression,” said Martin Reck, M.D., Ph.D., CheckMate -9LA study investigator, Lung Clinic Grosshansdorf, German Center of Lung Research.
“With these results from CheckMate -9LA, we now have evidence that this dual immunotherapy combination, when administered concomitantly with two cycles of chemotherapy, provides a survival benefit in this setting – a benefit that was observed early and sustained at one year of follow-up across key subgroups of patients. As the data become more mature, I see the potential for an improving survival benefit over time.”
With a minimum follow-up of 12.7 months, Opdivo plus Yervoy with limited chemotherapy improved OS regardless of PD-L1 expression levels, reducing the risk of death by 38% in patients with PD-L1 <1% (HR: 0.62, 95% CI: 0.45 to 0.85) and by 36% in patients with PD-L1 ≥ 1% (HR: 0.64, 95% CI: 0.50 to 0.82).
In addition, the dual immunotherapy and chemotherapy combination demonstrated a one-year PFS rate of 33% versus 18% for chemotherapy (HR: 0.68, 95% CI: 0.57 to 0.82), and an ORR of 38% compared to 25% with chemotherapy alone.
“Understanding that each patient facing a diagnosis of metastatic non-small lung cancer is unique, we’ve approached our development program with the goal of delivering a number of potentially durable solutions for the significant number of first-line patients who still need new options,” said Nick Botwood, M.D., vice president, Oncology Clinical Development, Bristol Myers Squibb.
“The updated one-year overall survival data from CheckMate -9LA, along with three-year results from our CheckMate -227 trial, further reinforce the clinical value of Opdivo plus Yervoy-based combinations, the first-ever dual immunotherapy options for the treatment of first-line non-small cell lung cancer.”
Opdivo plus Yervoy 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 tumor cells: Yervoy helps activate and proliferate T cells, while Opdivo helps existing T cells discover the tumor.
Some of the T cells stimulated by Yervoy can become memory T cells, which may allow for a long-term immune response.
The addition of limited chemotherapy to the Opdivo plus Yervoy combination may help patients achieve early disease control.
CheckMate -9LA
CheckMate -9LA is an open-label, multi-center, randomized Phase 3 trial evaluating Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with chemotherapy (two cycles) compared to chemotherapy alone (up to four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) regardless of PD-L1 expression and histology.
Patients in the experimental arm were treated with immunotherapy for up to two years or until disease progression or unacceptable toxicity. Patients in the control arm were treated with up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity.
The primary endpoint of the trial was overall survival (OS) in the intent-to-treat (ITT) population.
Secondary hierarchical endpoints included progression-free survival (PFS) and overall response rate (ORR), and the study also evaluated efficacy measures according to biomarkers.
