Bristol Myers Squibb (NYSE: BMY) has announced results from the Phase 3 CheckMate 9LA clinical trial evaluating the efficacy of Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of metastatic non-small cell lung cancer (NSCLC), one of the most common types of lung cancer.
Approximately 84% of lung cancer patients are diagnosed with the non-small cell form. Lung cancer results in a greater number of mortalities than any other types of cancer globally and metastatic lung cancer has a five-year survival rate of only 5%.
During first-line treatment, the antibodies “demonstrated a statistically significant and clinically meaningful survival benefit” when administered in conjunction with two rounds of chemotherapy, meeting primary and secondary endpoints and demonstrating a better overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) than chemotherapy alone.
Study investigator Martin Reck, MD, PhD, stated, “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.”
“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,” Dr. Reck continued.
“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 combination continued 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),” Bristol-Myers Squibb stated in their press release.
In the open-label, multi-center, randomized Phase 3 CheckMate 9LA trial, patients treated with both immunotherapy and chemotherapy agents received the drugs “for up to two years or until disease progression or unacceptable toxicity” while those that received chemotherapy alone had “up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity.”
“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.”
Vice President of Oncology Clinical Development at Bristol Myers Squibb Nick Botwood, MD, stated, “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.”
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“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,” Dr. Botwood continued.
The collective targeting of two inhibitory costimulatory molecules, programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), by Opdivo and Yervoy supports the cancer-fighting activity of T lymphocytes, a class of white blood cell critically important for the anti-cancer immune response. PD-1 and CTLA-4 are “immune checkpoint” receptors frequently exploited by cancerous cells to evade the protective anti-tumor responses of the immune system.
In combination, Opdivo and Yervoy support the proliferation and weaponization of both naive and memory T lymphocytes, enabling the development of robust anti-cancer immune responses with the potential to provide long-term immunological protection against key cancer antigens. In the CheckMate 9LA trial, chemotherapy drugs were added to the antibody combination to potentially “help patients achieve early disease control.”
In addition to Opdivo and Yervoy, immunotherapeutic antibodies targeting other proteins are under development for the treatment of solid tumors. An antibody inhibitor of the cell surface protein CD39 is being evaluated by Surface Oncology and Merck.
Engineered lymphocytes are also being evaluated as a potential treatment for solid tumors. Adaptimmune is exploring the anti-cancer activity of SPEAR T cells and NantKwest is evaluating the safety and efficacy of a natural killer cell-based therapy which has shown promise for the treatment of pancreatic cancer.