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nivolumab Plus Relatlimab Fails to Improve Recurrence-Free Survival in Melanoma
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Phase 3 trial shows no significant benefit of combination therapy over nivolumab alone in adjuvant treatment of stage 3/4 melanoma after resection.
CHICAGO – The phase 3 Relativity-098 clinical trial, a randomized, double-blind study, has revealed that the combination of nivolumab and relatlimab (nivo + rela), marketed as Opdualag by Bristol Myers Squibb, did not significantly improve recurrence-free survival (RFS) compared to nivolumab alone. The trial focused on adjuvant treatment for stage 3 or 4 melanoma following complete resection. The findings were presented at the 2025 American Society of Clinical Oncology (ASCO) meeting in Chicago, Illinois. The study aimed to address the need for more effective adjuvant therapies for individuals with completely resected melanoma.1
Stage 3 & 4 Melanoma
Melanoma is a type of skin cancer that originates in melanocytes, the cells responsible for skin pigmentation. Upon diagnosis, doctors determine the extent of the cancer’s spread using the American Joint Committee on Cancer (AJCC) TNM system, according to the American Cancer Society.2
Stage 3 melanoma involves a primary tumor of any thickness, possibly ulcerated, that has spread to nearby lymph nodes, small areas of surrounding skin, or the skin’s lymphatic channels near the tumor. Stage 4 melanoma, in contrast, involves a primary tumor of varying thickness, potentially ulcerated, that has spread to distant parts of the body, including the skin, lymph nodes, lungs, other organs outside the central nervous system, and the central nervous system itself.2
According to the Melanoma Research Alliance, treatment options for resectable stage 3 and 4 melanoma include surgical removal, adjuvant therapy, or neoadjuvant therapy.However, individuals with advanced melanoma remain at high risk of recurrence even after complete resection.3
The results demonstrated that after a minimum follow-up of 23.4 months, ther was not a statistically significant difference in RFS.
Relativity-047 Clinical Trial
The phase 2/3 Relativity-047 clinical trial previously investigated the effectiveness of rela + nivo compared to nivo alone in treating unresectable or metastatic melanoma.4
The results of that trial indicated that the fixed-dose combination of nivo + rela led to a clinically significant improvement in progression-free survival (PFS) and overall survival (OS) compared to nivo alone,with a manageable safety profile maintained over a 3-year follow-up period.1
Relativity-098 Clinical Trial
Based on the findings of the Relativity-047 study, the relativity-098 trial was initiated to determine if adjuvant nivo + rela could offer a more effective treatment then nivo alone for individuals with completely resected stage 3 and 4 melanoma.1
In the study,individuals aged 12 years and older were stratified by AJCC stage (3A/3B vs 3C vs 3D/4) and then randomly assigned to receive either nivo 480 mg + rela 160 mg or nivo 480 mg every 4 weeks for up to 1 year,or until recurrence,unacceptable toxicity,or withdrawal of consent.1
The trial included 547 individuals receiving nivolumab plus relatlimab (nivo + rela) and 546 receiving nivolumab monotherapy. In the combination vs monotherapy groups, 38% vs 36% had stage 2A/B disease, and 49% vs 50% had stage 2C disease. Cutaneous nonacral melanoma was the most common subtype (80% vs 83%), followed by cutaneous acral (11% vs 10%) and mucosal melanoma (2% vs 1%). the median duration of therapy was 11.0 months in both treatment arms.1
After a minimum follow-up of 23.4 months,the study found no statistically significant difference in RFS between the nivo + rela group and the nivo-alone group,with consistent RFS outcomes across various subgroups. Overall survival (OS), a secondary endpoint, was not formally tested due to only 48% data maturity (148 OS events). Distant metastasis-free survival (DMFS), another secondary endpoint, was similar in both groups.1
Grade 3/4 treatment-related adverse events (TRAEs) occurred in 19% of individuals receiving nivo + rela,compared to 8% in the nivo-alone group. Any-grade traes led to treatment discontinuation in 17% of nivo + rela individuals and 9% of nivo-alone patients. There were 2 treatment-related deaths in the nivo + rela group and 1 in the nivo-alone group.1
The safety profile of nivo + rela was consistent with previous results from the Relativity-047 clinical trial, but the combination did not demonstrate significant RFS improvements.1
Frequently Asked Questions
- What is melanoma?
- Melanoma is a type of skin cancer that begins in melanocytes,the cells that produce pigment in the skin.
- what are the stages of melanoma?
- Melanoma stages range from Stage 0 (melanoma in situ) to Stage IV (metastatic melanoma), indicating the extent of the cancer’s spread.
- What is adjuvant therapy?
- Adjuvant therapy is additional treatment given after the primary treatment (usually surgery) to lower the risk of the cancer recurring.
