Anti-LAG-3 antibody Relatlimab and Nivolumab in patients with previously untreated metastatic or unresectable melanoma: RELATIVITY-047 trial has met primary endpoint of progression-free survival
Primary results from the phase 2/3 RELATIVITY-047 trial evaluating the fixed-dose combination of Relatlimab, an anti-LAG-3 antibody, and Nivolumab ( Opdivo ) versus Nivolumab alone in patients with previously untreated metastatic or unresectable melanoma, were announced.
The trial met its primary endpoint of progression-free survival ( PFS ). Follow up for overall survival, a secondary endpoint, is ongoing.
The fixed-dose combination was well-tolerated and there were no new safety signals reported in either the Relatlimab and Nivolumab combination arm or the Nivolumab arm.
Lymphocyte-activation gene 3 ( LAG-3 ) is a cell-surface molecule expressed on effector T cells and regulatory T cells ( Tregs ). LAG-3 regulates an inhibitory immune checkpoint pathway that limits the activity of T cells, leading to an impaired ability to attack tumor cells.
In the chronic presence of diseases like cancer, T cells exhibit progressive exhaustion that is characterized by the upregulation of inhibitory immune checkpoints such as PD-1 and LAG-3.
While LAG-3 and PD-1 are distinct immune checkpoint pathways, they may potentially act synergistically on effector T cells leading to T cell exhaustion.
Relatlimab is a LAG-3–blocking antibody that binds to LAG-3 on T cells, restoring effector function of exhausted T cells.
Relatlimab, in combination with Nivolumab, is the first anti-LAG-3 antibody to demonstrate a benefit for patients.
The primary endpoint of RELATIVITY-047 is progression-free survival ( PFS ) by Blinded Independent Central Review ( BICR ) and the secondary endpoints are overall survival ( OS ) and objective response rate ( ORR ).
A total of 714 patients were randomized 1:1 to receive a fixed-dose combination of Relatlimab 160 mg and Nivolumab 480 mg or Nivolumab 480 mg by intravenous infusion every four weeks until disease recurrence, unacceptable toxicity or withdrawal of consent.
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells ( melanocytes ) located in the skin.
Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs.
The incidence of melanoma has been increasing steadily for the last 30 years.
In the United States, 106,110 new diagnoses of melanoma and about 7,180 related deaths are estimated for 2021.
Globally, the World Health Organization ( WHO ) estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths.
Melanoma is mostly curable when treated in its very early stages; however, survival rates decrease if regional lymph nodes are involved. ( Xagena )
Source: Bristol Myers Squibb, 2021