BMS Announces Positive Top-Line Results from Phase 3 CheckMate-9LA Trial of Opdivo Plus Low-Dose Yervoy with Chemotherapy in First-Line NSCLC

Compiled by Keke

Bristol-Myers Squibb’s (BMS) immuno-oncology combination Opdivo-Yervoy previously faced setbacks in trials for untreated non-small cell lung cancer, but the regimen is likely to succeed after the addition of a new member.

On October 22, Bristol-Myers Squibb (BMS) announced that a pivotal Phase 3 clinical trial initially demonstrated that Opdivo plus low-dose Yervoy in combination with chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) met the primary endpoint of overall survival (OS) in a pre-specified interim analysis. Furthermore, the safety profile of Opdivo plus low-dose Yervoy, along with that of the two chemotherapy agents, reflected the known safety profiles of immunotherapy and chemotherapeutic drugs in the first-line treatment of NSCLC.

The CheckMate -9LA study is an open-label, multicenter, randomized Phase 3 clinical trial that evaluates Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with chemotherapy (two cycles) as first-line treatment for patients with advanced NSCLC (regardless of PD-L1 expression status and histology), compared to chemotherapy alone (up to four cycles, followed by optional pemetrexed maintenance therapy). Patients in the experimental arm received treatment for up to two years or until disease progression or unacceptable toxicity; patients in the control arm received up to four cycles of chemotherapy and optional pemetrexed maintenance therapy (if eligible) until disease progression or toxicity. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival, overall response rate, and efficacy outcomes based on biomarkers.

However, apart from the OS data, BMS did not disclose the secondary endpoints or other additional results of this trial. BMS stated that it would continue to complete a comprehensive evaluation of the CheckMate-9LA data, present the findings at an upcoming conference, and share them with regulatory authorities.

As is well known, Opdivo is a PD-1 immune checkpoint inhibitor that received its first global approval in July 2014. However, its path to market dominance has not been smooth, partly due to the strong growth and market competition from its rival, Keytruda. Market data from 2018 showed that Opdivo achieved annual sales of $7.57 billion, representing a 31.4% increase, while Keytruda followed closely with annual sales of $7.171 billion, but with a much higher growth rate of 88.3%.

On the other hand, setbacks have stemmed from its own research failures. Opdivo is currently undergoing clinical trials across all phases for various types of cancer, but has repeatedly encountered setbacks. The most recent instance occurred in July, when a Phase 3 study evaluating Opdivo combined with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC) failed to demonstrate superiority over chemotherapy alone. However, another part of the study results indicated that the Opdivo-Yervoy combination appeared more advantageous, reducing the risk of patient death by 21%. This finding holds significant importance in the market competition dominated by Keytruda.

The positive results released by BMS could also be a good omen for AstraZeneca, which is currently awaiting data from similar trials evaluating the combination of chemotherapy with Imfinzi (counterpart to Opdivo) and tremelimumab (counterpart to Yervoy).

The latest results have also led investors to hope that BMS’s combination regimen, with the addition of chemotherapy agents, can catch up with Merck & Co.’s market “heavyweight” status as early as possible. Of course, this is not so simple. Adding extra drugs to the combination not only increases “treatment costs to some extent,” but also raises toxicity levels. Therefore, analysts point out that the commercial value of CheckMate-9LA will depend on the balance between clinical benefit and toxicity. Only by providing complete results can this risk-benefit assessment be conducted. From the current perspective, the safety and tolerability of BMS’s triple-drug cocktail therapy are likely worse than those shown in Merck’s Keynote-189 trial.

But regardless of the final outcome, BMS shares rose more than 5% at the open after the trial results were released.

Reference Source: UPDATED: Bristol-Myers Squibb Makes Opdivo Pitch for Frontline Lung Cancer with Open-Label Phase III Study