177Lu-PSMA-617 Trial May Be Efficacious in Advanced PSMA-Expressing ccRCC

As an unmet need for additional therapeutic targets for renal cell carcinoma (RCC) lingers, the radioligand therapy 177Lu-pSMA-617 (Pluvicto), an agent already approved for prostate cancer, may be a viable option for patients with prostate-specific membrane antigen (PSMA)-positive advanced clear cell RCC.1,2

At the 2025 Kidney Cancer Research Summit, Praful Ravi, MB, BChir, MRCP, shared with CancerNetwork® information on the phase 2 LASER trial (NCT06964958) evaluating the agent in RCC. It has been confirmed by immunohistochemistry and RNA sequencing that PSMA is present on the neovasculature of solid tumors other than prostate cancer, including clear cell RCC.

Ravi, a medical oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, emphasized that, since PSMA was found in RCC, 177Lu-PSMA-617, which has already been proven in other tumor types, is feasible for evaluation as a possible treatment option.

Another positive facet of utilizing an agent that has shown success in other disease types is that it may be easier to secure support and funding for a larger, randomized phase 3 trial. According to Ravi, it would be transformative to have a radioligand therapy demonstrate success in RCC, and if it is successful, it should pave the way for radioligand therapy to advance beyond just PSMA-expressing disease.

Transcript:

CancerNetwork: Why is this trial being conducted?

We’re conducting this trial because, in clear cell kidney cancer, in advanced disease, beyond immune therapy and tyrosine kinase inhibitors [TKIs], there are limited therapeutic options and limited therapeutic classes of therapy. We know that kidney cancers express a protein called PSMA, or it’s their blood vessels feeding the cancer neovasculature that express PSMA. We know the target is present on the blood vessels by both immunohistochemistry [and] RNA sequencing. Also, with PSMA, we can image it with a PET scan, which is what we’ve been doing for prostate cancer. Here…we have a therapy which targets that; it is 177Lu-PSMA-617, or Pluvicto, which is approved, works well, and is effective and safe in prostate cancer that expresses PSMA. We have kidney cancers that have PSMA on the neovasculature, so there’s a clear rationale to evaluate the drug in PSMA-expressing clear cell RCC.

How significant would it be if a radioligand therapy demonstrates positive efficacy and safety in RCC?

It could, quite honestly, be transformative if we see some positive activity here. It’s very easy to envisage this going into a large randomized, registrational trial because there’s a drug that’s proven—approved in prostate cancer. [If] we see activity in kidney cancer, then it will be very easy for a company like Novartis to do a large, randomized study because these patients have an unmet need. There’s belzutifan (Welireg), which is the only other agent that’s proven in the space outside of a TKI. It would transform the disease, and [radioligand therapy] in general. There isn’t only PSMA, there’s CAIX and other targets. [Radioligand therapy] is emerging across all solid tumors. [This is] the first foray into something that’s non-prostate, at least from the PSMA perspective, but it could open the [radioligand therapy] space beyond just PSMA.

Reference

1. Ravi P, Xie W, Berg S, et al. LASER – a phase 2 trial of 177Lu-PSMA-617 as systemic therapy for renal cell carcinoma. Presented at the 2025 Kidney Cancer Research Summit; July 17-19, 2025; Boston, MA.
2. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed July 23, 2026. https://tinyurl.com/2s3cp4bd