ANVISA Approval Immunotherapy Melanoma: What You Need to Know

Key Takeaways

• Approval gap: As of June 2026, ANVISA has not approved relatlimab plus nivolumab (Opdualag) for advanced melanoma, despite FDA approval in March 2022 based on the RELATIVITY-047 trial (ClinicalTrials.gov NCT03470922).
• Clinical evidence: The Phase III trial demonstrated median progression-free survival (PFS) of 10.1 months with the combination versus 4.6 months with nivolumab alone (HR 0.75, 95% CI: 0.62–0.90, P=0.0055), per FDA approval announcement.
• Market impact: The lack of ANVISA approval restricts Brazilian patients' access to this novel dual immunotherapy, maintaining reliance on existing checkpoint inhibitors and targeted therapies.
• Regulatory outlook: No public timeline exists for ANVISA submission or approval; stakeholders should monitor ANVISA's consultation database and Bristol Myers Squibb's investor filings.
• Global context: Opdualag has secured regulatory approval in the United States, European Union, and other major markets, making Brazil an outlier in access to this therapeutic option.

What Is the Current ANVISA Status for Relatlimab Plus Nivolumab?

As of June 2026, the Brazilian Health Regulatory Agency (ANVISA) has not granted marketing authorization for the fixed-dose combination of relatlimab and nivolumab (brand name Opdualag) for the treatment of unresectable or metastatic melanoma. This regulatory status contrasts with approvals granted by the U.S. Food and Drug Administration (FDA) in March 2022, the European Medicines Agency (EMA), and other major regulatory bodies.

The absence of ANVISA approval means that Brazilian patients with advanced melanoma cannot access this treatment through standard commercial channels. This creates a disparity in treatment options between Brazil and markets where the combination is approved. Healthcare providers in Brazil must rely on alternative immunotherapy and targeted therapy regimens for managing advanced melanoma.

How Did the RELATIVITY-047 Trial Support FDA Approval?

The FDA approval of relatlimab plus nivolumab was based on results from the Phase III RELATIVITY-047 trial (NCT03470922), a randomized, double-blind study that enrolled 714 patients with previously untreated, unresectable or metastatic melanoma. The trial design compared the combination of relatlimab (LAG-3 inhibitor) and nivolumab (PD-1 inhibitor) versus nivolumab monotherapy.

The study met its primary endpoint of progression-free survival (PFS) per RECIST v1.1 criteria assessed by blinded independent central review. Key efficacy results included:

• Median PFS: 10.1 months (95% CI: 6.4–14.1) for the combination versus 4.6 months (95% CI: 3.4–5.6) for nivolumab alone
• Hazard ratio: 0.75 (95% CI: 0.62–0.90), representing a 25% reduction in risk of progression or death
• P-value: 0.0055 (statistically significant)

The safety profile showed grade 3–4 treatment-related adverse events in 18.9% of patients receiving the combination versus 9.7% receiving nivolumab monotherapy. The most common adverse events included fatigue, rash, arthralgia, and diarrhea.

What Treatment Options Exist for Brazilian Melanoma Patients?

Without access to relatlimab plus nivolumab, Brazilian patients with advanced melanoma rely on established therapeutic options that have secured ANVISA approval. These include:

Approved Advanced Melanoma Treatments in Brazil

Drug/Regimen	Mechanism	ANVISA Status
Pembrolizumab	PD-1 inhibitor	Approved
Nivolumab monotherapy	PD-1 inhibitor	Approved
Ipilimumab + nivolumab	CTLA-4 + PD-1 inhibitors	Approved
Dabrafenib + trametinib	BRAF + MEK inhibitors	Approved (BRAF V600+)
Vemurafenib	BRAF inhibitor	Approved (BRAF V600+)
Relatlimab + nivolumab	LAG-3 + PD-1 inhibitors	Not approved

The combination of ipilimumab and nivolumab represents the most similar alternative to relatlimab plus nivolumab, offering dual checkpoint inhibition through CTLA-4 and PD-1 blockade. However, this regimen carries a higher toxicity burden compared to the LAG-3/PD-1 combination evaluated in RELATIVITY-047.

What Factors Could Influence ANVISA Approval?

Several factors may contribute to the delay in ANVISA approval for relatlimab plus nivolumab. Regulatory submissions to ANVISA require comprehensive documentation including clinical trial data, manufacturing information, and proposed labeling. The sponsor, Bristol Myers Squibb, must initiate and complete this submission process before ANVISA can review the application.

Pricing and reimbursement negotiations represent additional potential barriers. Brazil's regulatory framework includes considerations for cost-effectiveness and healthcare system impact. The National Health Surveillance Agency may also prioritize reviews based on public health needs, therapeutic innovation, and existing treatment availability.

ANVISA has implemented various initiatives to accelerate access to innovative medicines, including pathways for priority review and conditional approval. However, no public information confirms that relatlimab plus nivolumab has entered these pathways as of June 2026.

What Is the Global Regulatory Landscape?

Relatlimab plus nivolumab has achieved regulatory approval in major pharmaceutical markets worldwide, establishing a substantial precedent for safety and efficacy. Following the FDA approval on March 18, 2022, the combination secured European Union marketing authorization and approvals in Canada, Australia, Japan, and other countries.

This global adoption reflects the clinical community's recognition of LAG-3 as a validated immunotherapy target. The combination adds a novel mechanism to the melanoma treatment landscape, providing an alternative to CTLA-4-based combination approaches with potentially improved tolerability.

The disparity in Brazil's regulatory timeline may affect the country's competitiveness in clinical research and patient access to therapeutic advances. International patients in regions with approval can access Opdualag, while Brazilian patients await regulatory action.

Frequently Asked Questions

Primary Sources

1. U.S. Food and Drug Administration. FDA Approves Nivolumab and Relatlimab-rmbw for Advanced Melanoma. FDA Drug Approvals and Databases. Published March 18, 2022.
2. ClinicalTrials.gov. A Study of Relatlimab in Combination With Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047). NCT03470922. Updated June 2025.
3. Agência Nacional de Vigilância Sanitária (ANVISA). Consulta de Medicamentos. Accessed June 2026.
4. Tawbi HA, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. New England Journal of Medicine. 2022;386(1):24-34. doi:10.1056/NEJMoa2109970.