BARCELONA — Bristol Myers Squibb’s LAG-3 approach has shown potential in certain lung cancer patients in a Phase 2 study, drawing some reassurance in its planned late-stage trial against Merck’s Keytruda plus chemotherapy in an even more specific group of patients.
Samit HirawatThat Phase 3 will study the company’s PD-1 drug Opdivo combined with its anti-LAG-3 agent relatlimab in first-line non-small cell lung cancer patients with PD-L1 expression between 1% and 49% and non-squamous disease.
And, if successful, that study could help establish the LAG-3 strategy as a new standard of care in these patients, BMS medical chief Samit Hirawat told Endpoints News ahead of the European Society for Medical Oncology annual meeting in Barcelona.
In part two of the Phase 2 RELATIVITY-104 trial, a fixed-dose combination of Opdivo and relatlimab added to chemo achieved a 58% objective response rate versus 39.6% for Opdivo and chemo in 50 NSCLC patients with at least 1% PD-L1 expression and non-squamous histology, according to data from a prespecified subgroup presented at the confab.
Median progression-free survival was 11.6 months for the treatment arm versus 6.9 months with control. Overall survival data were still immature at data cut-off.
Up next, Bristol Myers will test the PD-1/LAG-3 combo with chemo against Keytruda and chemo in the upcoming Phase 3 RELATIVITY1093 study in 800 first-line NSCLC patients with PD-L1 expression between 1% and 49% and non-squamous disease. That trial’s primary endpoint is OS for up to five years.
Opdivo with relatlimab won FDA approval for metastatic melanoma or melanoma that can’t be treated with surgery in 2022 with the brand name Opdualag. That approved fixed-dose combination has different doses than what is used in the lung cancer program.
Last month, William Blair analysts said that although the melanoma launch has been strong, success in lung cancer “would unlock a meaningful market opportunity.” In the second quarter, sales of Opdualag climbed 53% from the same period last year to $235 million.
But it could be an uphill climb for the LAG-3 approach in lung cancer. Keytruda plus chemo has set a “high bar to beat” in a head-to-head test in lung cancer, William Blair analysts said. For context, Keytruda was the first immunotherapy to show a sustained five-year survival benefit in combination with chemo and as a monotherapy in first-line NSCLC.
Nonetheless, patients with 1% to 49% PD-L1 expression to be targeted in the Phase 3 lung cancer study generally don’t have as good outcomes as those with greater than 50% PD-L1 expression, so adding LAG-3 inhibition could offer extra benefit, the analysts added.
The Phase 2 lung cancer data at ESMO also includes the PD-1/LAG-3 combo’s impact in patients with PD-L1 expression of more than 50% and non-squamous disease. The PFS in the treatment cohort was 15.8 months versus seven months in the control arm, Hirawat said. Based on these results, Bristol Myers is planning further development in this population with more details to come next year, he added.
The drugmaker has also studied the PD-1/LAG-3 combo in a Phase 3 test in colorectal cancer, but that effort ended in disappointment late last year.
Another company with a LAG-3 candidate is Immutep, with its eftilagimod alpha in Phase 3 for NSCLC in combination with Keytruda. At last year’s ESMO, the biotech said that in the mid-stage lung cancer trial for its combo, the subgroup of patients with at least 1% PD-L1 achieved an ORR of 48.3%. That trial did not include a control arm.
At this year’s conference, Immutep is set to present data from a Phase 2b trial of its LAG-3 drug and Keytruda in recurrent or metastatic first line head and neck squamous cell carcinoma.