Bristol Myers highlights LAG-3 lung cancer strategy ahead of Keytruda showdown

Bristol Myers Squibb has reported promising results for its LAG-3 approach in certain lung cancer patients from a Phase 2 study. This development brings hope for its upcoming late-stage trial, which will compare its treatment against Merck’s Keytruda combined with chemotherapy in a more specific group of patients.

The upcoming Phase 3 trial will investigate Bristol Myers Squibb’s PD-1 drug Opdivo in combination with its anti-LAG-3 agent relatlimab for first-line treatment in non-small cell lung cancer (NSCLC) patients. These patients have PD-L1 expression levels between 1% and 49% and are diagnosed with non-squamous disease. If this study proves successful, it could establish the LAG-3 strategy as a new standard of care for these patients, as stated by BMS medical chief Samit Hirawat ahead of the European Society for Medical Oncology annual meeting in Barcelona.

In the second part of the Phase 2 RELATIVITY-104 trial, a fixed-dose combination of Opdivo and relatlimab added to chemotherapy achieved a 58% objective response rate (ORR) compared to 39.6% for Opdivo and chemotherapy alone. This data was collected from 50 NSCLC patients with at least 1% PD-L1 expression and non-squamous histology. The treatment arm had a median progression-free survival (PFS) of 11.6 months versus 6.9 months for the control group. However, overall survival data is still immature at the data cut-off point.

The next step for Bristol Myers is the Phase 3 RELATIVITY-1093 study, which will test the PD-1/LAG-3 combination with chemotherapy against Keytruda and chemotherapy in 800 first-line NSCLC patients with PD-L1 expression of 1% to 49% and non-squamous disease. The primary endpoint of this trial is overall survival (OS) over a period of up to five years.

Opdivo combined with relatlimab, marketed as Opdualag, has already received FDA approval for metastatic melanoma or melanoma that cannot be treated surgically in 2022. The approved fixed-dose combination for melanoma has different dosing than what is being used in the lung cancer program. Last month, analysts from William Blair commented that although the melanoma launch has been strong, success in lung cancer could unlock a significant market opportunity. In the second quarter, sales of Opdualag increased by 53% from the same period last year, reaching $235 million.

Despite the promising results, the LAG-3 approach in lung cancer faces stiff competition. Keytruda plus chemotherapy has set a high benchmark in first-line NSCLC, showing a sustained five-year survival benefit. However, patients with 1% to 49% PD-L1 expression generally have poorer outcomes than those with more than 50% PD-L1 expression. Hence, adding LAG-3 inhibition could provide additional benefits, analysts suggest.

The Phase 2 lung cancer data presented at ESMO also explored the PD-1/LAG-3 combination’s effect on patients with more than 50% PD-L1 expression and non-squamous disease. The treatment arm had a PFS of 15.8 months versus seven months in the control group. Based on these findings, Bristol Myers plans further development in this population, with more details expected next year.

Bristol Myers had previously tested the PD-1/LAG-3 combination in a Phase 3 trial for colorectal cancer, which ended in disappointment late last year.

Another company, Immutep, is also developing a LAG-3 candidate called eftilagimod alpha. This drug is in Phase 3 trials for NSCLC in combination with Keytruda. At last year’s ESMO, Immutep reported that their mid-stage lung cancer trial for this combination achieved an ORR of 48.3% in patients with at least 1% PD-L1 expression. This trial did not have a control arm.

At this year’s conference, Immutep is expected to present data from a Phase 2b trial of its LAG-3 drug combined with Keytruda in recurrent or metastatic first-line head and neck squamous cell carcinoma.