CheckMate-9LA Trial Data Show Nivolumab Plus Ipilimumab with Limited-Course Chemotherapy Significantly Improves Overall Survival in First-Line Metastatic NSCLC
May 14, 2020 12:38
CST Updated
12:38
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
On May 13, 2020, Bristol-Myers Squibb announced the primary results from the Phase III CheckMate -9LA clinical study. The results demonstrated that Opdivo in combination with Yervoy and two cycles of concurrent chemotherapy provided statistically significant and clinically meaningful survival benefits as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC). The study met its primary and key secondary endpoints. Compared with chemotherapy alone, the dual immunotherapy regimen combined with chemotherapy improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
The prespecified interim analysis of the primary endpoint, overall survival (OS), demonstrated that, with a minimum follow-up of 8.1 months, Opdivo in combination with Yervoy and two cycles of chemotherapy reduced the risk of death by 31% compared with chemotherapy alone [Hazard Ratio (HR) 0.69, 96.71% Confidence Interval (CI): 0.55 to 0.87; p=0.0006]. Furthermore, at a longer follow-up duration (minimum 12.7 months), this combination regimen provided sustained OS benefit compared with chemotherapy alone (median OS: 15.6 months vs. 10.9 months [HR 0.66, 95% CI: 0.55–0.80]). In key patient subgroups, clinical benefit was observed across all efficacy assessments, regardless of PD-L1 expression levels or tumor histology (squamous or non-squamous).
The safety profile of Opdivo (360 mg every 3 weeks) in combination with Yervoy (1 mg/kg every 6 weeks) and two cycles of chemotherapy was consistent with the known safety event spectrum of immunotherapy and chemotherapy for first-line treatment of non-small cell lung cancer (NSCLC). These results (Abstract #9501) will be presented orally at the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting, held from May 29 to 31.
Dr. Martin Reck, Head of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf in Germany and an investigator for the CheckMate 9LA trial, stated, “The results confirm that first-line treatment with nivolumab plus ipilimumab extends survival in patients with non-small cell lung cancer (NSCLC), while the addition of a limited course of chemotherapy is expected to reduce the risk of early disease progression. The findings from CheckMate 9LA demonstrate that dual immunotherapy combined with two cycles of concurrent chemotherapy delivers survival benefits. We observed these benefits early across all key patient subgroups, and they were sustained at one year of follow-up. As the data continue to mature, I believe the survival benefit is likely to further improve.”
At a minimum follow-up of 12.7 months, Opdivo combined with Yervoy and limited-duration chemotherapy improved overall survival (OS) regardless of patients’ PD-L1 expression levels. In patients with PD-L1 <1%, the risk of death was reduced by 38% (HR 0.62, 95% CI: 0.45–0.85); in patients with PD-L1 ≥1%, the risk of death was reduced by 36% (HR 0.64, 95% CI: 0.50–0.82). Furthermore, among patients receiving dual immunotherapy combined with chemotherapy, the 1-year progression-free survival (PFS) rate was 33%, compared to only 18% in those receiving chemotherapy alone (HR 0.68, 95% CI: 0.57–0.82). The objective response rate (ORR) was 38% in the dual immunotherapy plus chemotherapy group versus 25% in the chemotherapy-alone group.
Dr. Nick Botwood, Vice President of Oncology Clinical Development at Bristol-Myers Squibb, stated, “Patients with metastatic non-small cell lung cancer (NSCLC) have heterogeneous disease profiles. In addressing this large patient population, we strive to develop multiple potentially durable treatment options to provide new therapeutic choices. The one-year overall survival data from CheckMate 9LA and the three-year follow-up data from CheckMate 227 further confirm the clinical value of Opdivo in combination with Yervoy as a first-line treatment for NSCLC, representing the first dual-immunotherapy regimen in this field.”
Opdivo in combination with Yervoy represents a unique dual immune checkpoint inhibitor regimen with potential synergistic mechanisms, targeting two distinct checkpoints (PD-1 and CTLA-4) to help eliminate tumor cells: Yervoy helps activate and proliferate T cells, while Opdivo assists existing T cells in recognizing tumors. Certain T cells activated by Yervoy can differentiate into memory T cells, thereby potentially enabling long-term immune responses. On the basis of combined treatment with Opdivo and Yervoy, the addition of limited-course chemotherapy helps patients achieve early disease control.
Note: Ipilimumab has not yet been marketed in China.
The prespecified interim analysis of the primary endpoint, overall survival (OS), demonstrated that, with a minimum follow-up of 8.1 months, Opdivo in combination with Yervoy and two cycles of chemotherapy reduced the risk of death by 31% compared with chemotherapy alone [Hazard Ratio (HR) 0.69, 96.71% Confidence Interval (CI): 0.55 to 0.87; p=0.0006]. Furthermore, at a longer follow-up duration (minimum 12.7 months), this combination regimen provided sustained OS benefit compared with chemotherapy alone (median OS: 15.6 months vs. 10.9 months [HR 0.66, 95% CI: 0.55–0.80]). In key patient subgroups, clinical benefit was observed across all efficacy assessments, regardless of PD-L1 expression levels or tumor histology (squamous or non-squamous).
The safety profile of Opdivo (360 mg every 3 weeks) in combination with Yervoy (1 mg/kg every 6 weeks) and two cycles of chemotherapy was consistent with the known safety event spectrum of immunotherapy and chemotherapy for first-line treatment of non-small cell lung cancer (NSCLC). These results (Abstract #9501) will be presented orally at the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting, held from May 29 to 31.
Dr. Martin Reck, Head of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf in Germany and an investigator for the CheckMate 9LA trial, stated, “The results confirm that first-line treatment with nivolumab plus ipilimumab extends survival in patients with non-small cell lung cancer (NSCLC), while the addition of a limited course of chemotherapy is expected to reduce the risk of early disease progression. The findings from CheckMate 9LA demonstrate that dual immunotherapy combined with two cycles of concurrent chemotherapy delivers survival benefits. We observed these benefits early across all key patient subgroups, and they were sustained at one year of follow-up. As the data continue to mature, I believe the survival benefit is likely to further improve.”
At a minimum follow-up of 12.7 months, Opdivo combined with Yervoy and limited-duration chemotherapy improved overall survival (OS) regardless of patients’ PD-L1 expression levels. In patients with PD-L1 <1%, the risk of death was reduced by 38% (HR 0.62, 95% CI: 0.45–0.85); in patients with PD-L1 ≥1%, the risk of death was reduced by 36% (HR 0.64, 95% CI: 0.50–0.82). Furthermore, among patients receiving dual immunotherapy combined with chemotherapy, the 1-year progression-free survival (PFS) rate was 33%, compared to only 18% in those receiving chemotherapy alone (HR 0.68, 95% CI: 0.57–0.82). The objective response rate (ORR) was 38% in the dual immunotherapy plus chemotherapy group versus 25% in the chemotherapy-alone group.
Dr. Nick Botwood, Vice President of Oncology Clinical Development at Bristol-Myers Squibb, stated, “Patients with metastatic non-small cell lung cancer (NSCLC) have heterogeneous disease profiles. In addressing this large patient population, we strive to develop multiple potentially durable treatment options to provide new therapeutic choices. The one-year overall survival data from CheckMate 9LA and the three-year follow-up data from CheckMate 227 further confirm the clinical value of Opdivo in combination with Yervoy as a first-line treatment for NSCLC, representing the first dual-immunotherapy regimen in this field.”
Opdivo in combination with Yervoy represents a unique dual immune checkpoint inhibitor regimen with potential synergistic mechanisms, targeting two distinct checkpoints (PD-1 and CTLA-4) to help eliminate tumor cells: Yervoy helps activate and proliferate T cells, while Opdivo assists existing T cells in recognizing tumors. Certain T cells activated by Yervoy can differentiate into memory T cells, thereby potentially enabling long-term immune responses. On the basis of combined treatment with Opdivo and Yervoy, the addition of limited-course chemotherapy helps patients achieve early disease control.
Note: Ipilimumab has not yet been marketed in China.