Relatlimab/Nivolumab Improves PFS in Previously Untreated Metastatic or Unresectable Melanoma

March 25, 2021
Kristi Rosa
Kristi Rosa

Managing Editor, OncLive®
Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource Contagion, strengthened the Rare Disease Report, of HCPLive, and now serves as the main digital news writer for OncLive. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

The fixed-dose combination of relatlimab plus nivolumab was found to improve progression-free survival over nivolumab alone in patients with previously untreated metastatic or unresectable melanoma, meeting the primary end point of the phase 2/3 RELATIVITY-047 trial.

The fixed-dose combination of relatlimab plus nivolumab (Opdivo) was found to improve progression-free survival (PFS) over nivolumab alone in patients with previously untreated metastatic or unresectable melanoma, meeting the primary end point of the phase 2/3 RELATIVITY-047 (CA224-047; NCT03470922) trial.1

Relatlimab is an anti-LAG-3 antibody, and these phase 3 data are the first to be reported from a trial evaluating such an agent, according to Bristol Myers Squibb, the drug developer. The pharmaceutical company plans to share the results at an upcoming medical meeting and discuss them with regulatory authorities.

Follow-up for the trial’s secondary end point of overall survival (OS) is ongoing, as is the follow-up for objective response rate (ORR). Additionally, the regimen was determined to be well tolerated, without any new safety signals observed in either the investigative or control arm.

“Immune checkpoint inhibitors alone or in combination have transformed treatment and improved survival rates for patients with metastatic or unresectable melanoma. However, there remain a considerable number of patients who could benefit from a novel combination therapy that leverages potentially complementary pathways to improve antitumor activity,’ Johnathan Cheng, senior vice president and head of oncology development at Bristol Myers Squibb, stated in a press release. “The results of this study suggest that targeting the LAG-3 pathway in combination with PD-1 inhibition may be a key strategy to enhance the immune response and help improve outcomes for these patients.”

LAG-3 is a molecule on the surface of effector T cells and regulatory T cells; it regulates an inhibitory immune checkpoint pathway that restricts the activity of T cells, which results in a hindered ability to attack tumor cells.

In patients with cancer, T cells show progressive exhaustion that is noted by the upregulation of PD-1 and LAG-3. Although these 2 inhibitory immune checkpoints are distinct pathways, they possess the potential to act synergistically on effector T cells and result in T cell exhaustion. By binding to LAG-3 on T cells, relatlimab is able to restore the function of those exhausted cells.

In the double-blind, phase 2/3 trial, investigators are examining the fixed-dose combination of relatlimab and nivolumab vs single-agent nivolumab in patients with previously untreated metastatic or unresectable melanoma.

To be eligible for enrollment, patients had to have histologically confirmed stage III or IV melanoma and be able to provide a tumor tissue sample to undergo biomarker analysis. They could not have previously received systemic therapy for their disease.2 Additionally, patients who had active brain metastases or leptomeningeal metastases, uveal melanoma, or active, known, or suspected autoimmune disease, were excluded.

In the trial, a total of 714 patients were randomized in a 1:1 fashion to receive either a fixed-dose combination of relatlimab at 160 mg plus nivolumab at 480 mg or nivolumab alone at 480 mg via intravenous infusion. Treatment was administered every 4 weeks until either disease recurrence, intolerable toxicity, or withdrawn consent.

The primary end point of the trial is PFS per blinded independent central review, while key secondary end points include OS and ORR.

Relatlimab is currently under exploration in several combination regimens across a variety of tumor types.

References

  1. Bristol Myers Squibb announces RELATIVITY-047, a trial evaluating anti-LAG-3 antibody relatlimab and Opdivo (nivolumab) in patients with previously untreated metastatic or unresectable melanoma, meets primary endpoint of progression-free survival. News release. Bristol Myers Squibb. March 25, 2021. Accessed March 25, 2021. https://bit.ly/3d1rIrI
  2. A study of relatlimab plus nivolumab versus nivolumab alone in participants with advanced melanoma. ClinicalTrials.gov. Updated September 1, 2020. Accessed March 25, 2021. https://clinicaltrials.gov/ct2/show/NCT03470922 

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