BMS’s Combo Therapy Involving LAG-3 Drug Impresses in Melanoma Trial

On March 25th, Bristol Myers Squibb (BMS) announced their anti-LAG-3 antibody in combination with Opdivo met its primary endpoint of progression-free survival. The trial is still ongoing to evaluate overall survival, but the company plans to present results in an upcoming scientific meeting. If approved, this would be BMS third immune checkpoint therapy.

Skin cancer is the most common type of cancer in the US. In 2021, over 200,000 are expected to be diagnosed with melanoma, a type of skin cancer. The number of cases of melanoma has increased by 44% over the last decade.

Currently, BMS has two checkpoint inhibitors approved for the treatment of metastatic or unresectable melanoma: Opdivo, an anti-PD1 antibody, and Yervoy, an anti-CTLA4 antibody. However, there are other checkpoint inhibitors in the market such as Keytruda and Atezolizumab approved for the treatment of melanoma, all of which inhibit the PD1-PDL1 interaction. As a result, BMS is developing antibodies against other targets to combine with their existing ones and gain a competitive edge.

RELATIVITY-047 Trial

Relatlimab is an antibody that inhibits the LAG-3 protein, which is involved in the response and activation of the effector T and regulatory T cells. Studies have shown that blocking this protein activates the immune system’s anti-tumor response.

The efficacy and safety of Relatlimab in combination with Opdivo is currently being tested on a randomized, double-blind Phase 2/3 clinical trial. Preliminary data show that the combination treatment containing 160mg of Relatlimab and 480mg Opdivo was significantly better than Opdivo alone at extending the survival rate while preventing disease progression (i.e., progression-free survival). The trial is still ongoing as they try to determine if there are any improvements in overall survival and the number of patients that show a reduction in tumor size.

“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 anti-tumor activity,” said Jonathan Cheng, Senior Vice President and head of oncology development, Bristol Myers Squibb.

“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.”

Blockbuster Drugs

BMS has been very successful with its two immune checkpoint therapies, Opdivo and Yervoy. Both have been approved as first-line therapies for several non-small cell lung and renal cell carcinomas. In addition, they have been approved as a single agent or in combination to treat several melanomas, Hodgkin lymphoma, colorectal cancer, and others.

As a result of their therapeutic success, BMS has made a significant profit from these therapies. In 2020 alone, Opdivo earned almost $7 billion worldwide, while Yervoy brought almost $1.7 billion. If the same trend is maintained, Relatlimab could be the next billion-dollar product for BMS.

Related Article: Bristol Myers Squibb Registers Another Trial Win for its Psoriasis Med

Author

Daniel Ojeda