Highlights from

ASCO 2021

American Society of Clinical Oncology annual meeting

Virtual 4-8 June 2021

Novel dual checkpoint blockade improves progression-free survival in melanoma

Summary: First results of the phase III RELATIVITY-047 trial validate the efficacy of dual checkpoint blockade demonstrated with the LAG-3 inhibitor relatlimab and nivolumab in patients with advanced melanoma.

Lymphocyte-activation gene 3 (LAG-3) regulates an immune checkpoint pathway which inhibits T-cell activity, and is upregulated in many tumour types including melanoma.1 Relatlimab, a human IgG4 LAG-3-blocking antibody, restores effector function of exhausted T cells.2 Relatlimab in combination with nivolumab modulates potentially synergistic immune checkpoint pathways and can enhance anti-tumour immune responses.3 RELATIVITY-047 (NCT03470922) is a global, randomised, double-blind, phase II/III study evaluating the combination of relatlimab plus nivolumab in first-line advanced melanoma. In this trial, 714 patients with previously untreated advanced melanoma were randomised 1:1 to receive relatlimab (160 mg) plus nivolumab (480 mg Q4W) or nivolumab alone. Patients were stratified by LAG-3 expression, PD-L1 expression, and BRAF mutation status. The primary endpoint was progression-free survival. Secondary endpoints were overall survival and objective response rate.

Dr Evan Lipson (Johns Hopkins University, MD, US) presented the first results of RELATIVITY-047. At a median follow-up of 13.2 months, progression-free survival in the relatlimab plus nivolumab arm was significantly improved versus nivolumab monotherapy: median 10.1 months versus 4.6 months, respectively. Progression-free survival rate at 12 months was 47.7% in the relatlimab/nivolumab arm versus 36.0% in the nivolumab arm. Progression-free survival favoured relatlimab/nivolumab regardless of age, tumour burden, BRAF mutation status, PD-L1 expression, and LAG-3 expression. The incidence of grade 3/4 treatment-related adverse events was higher in the relatlimab/nivolumab arm versus the nivolumab arm: 18.9% versus 9.7%. Treatment-related adverse events of any grade led to treatment discontinuation in 14.6% and 6.7% of patients in the relatlimab/nivolumab arm and nivolumab arm, respectively. “First-line treatment with relatlimab/nivolumab demonstrates a statistically significant progression-free survival compared with nivolumab monotherapy in patients with advanced melanoma,” concluded Dr Lipson. “In addition, relatlimab/nivolumab is well tolerated with a manageable safety profile and without unexpected safety signals. Therefore, this dual checkpoint blockade is a potential new treatment option for patients with advanced melanoma.”

  1. Durham N M, Nirschl C J et al. Lymphocyte activation gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One 2014;9:e109080 [full text]
  2. Yu X, Huang X et al. Characterization of a novel anti-human lymphocyte activation gene 3 (LAG-3) antibody for cancer immunotherapy. MAbs 2019;11:1139-1148 [full text]
  3. Ascierto P A, Bono P et al. Efficacy of BMS-986016, a monoclonal antibody that targets lymphocyte activation gene-3 (LAG-3), in combination with nivolumab in pts with melanoma who progressed during prior anti–PD-1/PD-L1 therapy (mel prior IO) in all-comer and biomarker-enriched populations. Abstract LBA18, ESMO 2017 [abstract]
  4. Lipson E, et al. Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase III results from RELATIVITY-047 (CA224-047). Abstract 9503, ASCO 2021, 4-8 June 2021

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Article image: @ JodiJacobson

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.