A study at Banner MD Anderson Cancer Center offers hope for patients with advanced melanoma who no longer respond to standard immunotherapies.

In a Phase II clinical trial, researchers found that an investigational treatment — RP1, a genetically engineered virus — used in combination with the immunotherapy drug nivolumab significantly shrank tumors in about one in three patients whose disease had progressed after standard treatment.

The trial enrolled 140 patients with advanced melanoma resistant to anti-PD-1 therapy, a common first-line immunotherapy. Historically, these patients have  few effective treatment options and face a median overall survival of just one year.

Notably, 15% of participants experienced a complete response, with all signs of cancer disappearing. Among those who responded, more than half remained in remission two years later.

“These are clinically meaningful results, especially when you consider the limited alternatives for patients once common therapy stops working,” principal investigator Dr. Jiaxin Niu said. He is also the co-director of the lung cancer program at Banner MD Anderson.

The study also found that RP1 could shrink tumors that were not directly injected, including in organs like the liver and lungs — suggesting a systemic immune response. Patients responded regardless of tumor size, location or specific genetic traits like BRAF mutations.

Importantly, the combination was well tolerated. While most patients experienced mild side effects such as fatigue or fever, only 12.9% had serious treatment-related side effects. No treatment-related deaths occurred.

Jiaxin Niu

Courtesy Banner Health

RP1 is a modified herpes simplex virus that has been engineered to target and destroy cancer cells while stimulating a broader immune response. It delivers immune-activating proteins, which enhance tumor cell destruction and immune system engagement.

Biomarker analyses from the study revealed increases in immune activity in the tumor in patients who responded to treatment, helping researchers better understand the therapy’s mechanism of action and laying the groundwork for future research.

While the trial was not randomized and did not include a control group, the results compare favorably to historical outcomes.

“The durability of the response is particularly encouraging, and we are hopeful that these results will support FDA approval,” Niu said. “I am deeply grateful to our courageous patients and their families, as well as to my dedicated colleagues and supportive staff. Their strength and commitment made this option possible for other patients in the near future.” 

Dr. Matthew Callster, senior physician executive for Banner MD Anderson, called it a significant new option for patients with melanoma.

“In the broader context, it also marks an important step toward establishing our center as a leading hub for oncology research in the Southwest,” Callister said.

More information about the study is available by visiting  https://doi.org/10.1200/JCO-25-01346.