FDA Does Not Approve RP1 in Combination with Nivolumab for Advanced Melanoma: What This Means for Patients

On April 10, 2026, the U.S. Food and Drug Administration (FDA) issued a decision not to approve the resubmission of the Biologics License Application (BLA) for RP1 (vusolimogene oderparepvec) in combination with nivolumab for advanced melanoma.

The FDA’s review process is designed to ensure that new treatments meet rigorous standards for safety, effectiveness, and consistency. When an application is not approved, it may mean the agency is seeking additional data, clarification, or further analysis before moving ahead.

In its denial, the FDA reiterated its reasoning from the Complete Response Letter (CRL) from July 21, 2025.

Understanding the Context

RP1 is an investigational oncolytic immunotherapy designed to selectively infect and destroy tumor cells while activating the immune system. In combination with nivolumab, it has been studied as a potential option for patients with advanced melanoma who progress on an anti–PD-1 containing regimen. Data from the phase 1/2 IGNYTE trial demonstrated an objective response rate of 32.9% and a complete response rate of 15% in 140 patients with advanced melanoma who no longer responded to other treatments.

Approximately 50% of patients fail to benefit from anti-PD-1 therapies. Although there is one FDA-approved treatment option and clinical trials for this patient population, there continues to be an unmet need. More treatment options are needed for these patients.

“This is not the outcome the melanoma community had hoped for,” said Sam Guild, President of AIM at Melanoma. “But it is important to remember that progress in cancer research is rarely linear. Each step—whether forward or paused—brings more understanding.”

AIM’s Advocacy Efforts

Last year, on July 21, 2025, the FDA denied approval of the BLA for RP1+nivolumab, an unexpected decision given that FDA had previously granted it breakthrough therapy designation, which is a process designed to expedite the development and review of drugs that treat serious conditions and show promising preliminary clinical evidence.

AIM’s advocacy efforts immediately went into high gear. AIM alerted the melanoma community of the denial and asked for reactions and stories to share with FDA and Congress. Hundreds of patients and families wrote to us, many noting that they and their doctors had been waiting for approval of RP1+nivolumab because they were out of treatment options.

AIM asked our fellow melanoma organizations to join us in writing to the FDA and asking them to make RP1+nivolumab available to patients while it worked out the issues it had with the sponsoring company. Please see our September 4, 2025, letter here.

AIM’s president met with over 15 congressional offices, sharing what their constituents wrote to us and urging the Representatives and Senators to inquire about the inconsistency in the FDA guidance on breakthrough status and trial design.

In October 2025, the FDA accepted a resubmission of the BLA for RP1+nivolumab.

AIM’s advocacy efforts continued: The Wall Street Journal published a letter to the editor from AIM’s vice president along with several editorials of their own about the RP1+nivolumab denial. The letter to the editor explained the urgent need for options for advanced melanoma patients, as well as our concerns about patient trust in the clinical trial system.

In February 2026, the FDA responded to our September letter (read here), and as the April decision date approached, AIM and our fellow advocates sent another letter to the FDA on March 26, 2026 (read here).

What Happens Next

We will learn more in the coming weeks and months about the next steps for RP1+nivolumab. The RP1+nivolumab phase 3 clinical trial (called IGNYTE) is still recruiting patients.

For Patients Right Now

If you or a loved one is navigating advanced melanoma:

• Talk with your care team about current approved treatment options
• Ask about clinical trials, which may provide access to emerging therapies
• Stay connected to trusted resources for updates and support

You can always reach out to AIM at Melanoma with your questions.

AIM at Melanoma remains focused on:

• Accelerating research for new and better treatments
• Supporting patients and families at every stage
• Ensuring the community has clear, accurate information

Continuing Forward

Setbacks in research are difficult—but they are also part of how progress happens.

Behind every decision is a deeper commitment to finding treatments that are not only new, but truly effective and safe.

That work continues every day.

AIM will continue to advocate on behalf of patients and their families for approval of safe and effective treatments—especially when there is critical need for options, as there is in this patient population.