New research presented at the 2018 SNMMI annual meeting revealed that pairing targeted radionuclide therapy (TRT) with immunotherapy may improve the survival of patients with metastatic melanoma.

“External beam radiotherapy has been shown to synergize with immune therapies preclinically, but it has proved to be very difficult for [treating] metastatic cases with multiple tumors,” Reinier Hernandez of the University of Wisconsin-Madison said in a session on Sunday. “We hypothesized that TRT can modulate the tumor microenvironment to enhance the response to immune checkpoint, but in a more systemic way, by targeting all of the tumor sites.”

For the study, mice with melanoma received yttrium-86-NM600 treatment. PET/CT scans were performed three, 21 and 48 hours after treatment to determine how much of the TRT agent needed to be injected to reach the desired radiation dose.
The mice treated with the TRT/immunotherapy exhibited tumor regression and experienced an improvement in survival compared to other treatment groups. More specifically, 66 percent had no signs of tumor resurgence.

“At the level we administered our TRT agent, there was no systemic toxicity observed,” said Hernandez.

He pointed out that TRT/immunotherapy requires close collaboration among immunology, radiation oncology, dosimetry and imaging experts. This multidisciplinary approach is necessary for developing more advanced therapies.

Yttrium-86-NM600 also has the potential to expand this combined approach to many other types of cancers. Hernandez and his team have already shown promising results in preclinical tests for breast cancer and neuroblastoma and they are currently testing this approach for pancreatic and lung cancer.

“Before the end of the year, we are hoping to start a trial in canines as a segway to IND-enabling studies with the final goal [of] taking this to a clinical study next year,” said Hernandez.

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