Siteman Cancer Center has three new clinical trials open focused on prostate and kidney cancers.
The first, a Phase II clinical trial testing a neoadjuvant immunotherapy treatment for prostate cancer, is available for men who have been diagnosed with localized prostate cancer. The study will evaluate the use of atezolizumab alone and in combination with etrumadenant or tocilizumab prior to radical prostatectomy (RP). Atezolizumab is a monoclonal antibody that is FDA-approved to treat bladder and lung cancer. In December 2022, it also was approved for the treatment of unresectable or metastatic alveolar soft part sarcoma (ASPS). Now, atezolizumab is being evaluated for its effectiveness in treating prostate cancer.
“Surgery can usually cure most patients with localized prostate cancer, but not all,” says Russell Pachynski, MD, a leading expert on genitourinary cancers who focuses on prostate cancer tumor immunology and immunotherapy in his laboratory at Washington University School of Medicine. “There are some patients who have a relatively high risk of the cancer returning later, so in this trial we are looking at whether immunotherapy prior to surgery can induce a long-lasting immune response, similar to that which occurs when someone gets a vaccine.”
While there are other clinical trials examining neoadjuvant approaches, most of those have been focused on hormone-based therapies. The atezolizumab trial is the first to test this immunotherapy in the neoadjuvant setting. The trial is only available at Siteman Cancer Center and the University of California-San Francisco. Patients eligible for the trial will have blood tests and tumor biopsies performed prior to surgery. Key to this trial is that patients who are eligible must undergo RP at Barnes-Jewish Hospital so that physicians can collect fresh tissue samples for ongoing study.
“The trial is an ongoing ‘adaptive’ design, so in future cohorts, we will evaluate other additional promising immunotherapy drugs in combination with atezolizumab,” says Dr. Pachynski. “Right now, these are small studies, with about 15 patients per cohort to study the various drug combinations and delineate induced immune responses.”
For metastatic prostate cancer, Dr. Pachynski is part of a multi-center Phase I clinical trial evaluating AMG 509, an engineered bispecific antibody that has been shown to induce an immune response against STEAP1 proteins, which are overexpressed in more than 80 percent of metastatic prostate cancers.
“AMG 509 also binds to CD3+ T cells and redirects them to tumor cells, so we’re hoping this particular immunotherapy can be a one-two punch to target prostate cancer cells,” says Dr. Pachynski. The early phase trial, which began in 2020, is expected to enroll more than 450 patients with metastatic prostate cancer who have failed previous treatment options.
Kidney Cancer
A phase III clinical trial examining the effectiveness of a combination therapy to treat patients at high risk for recurrence of clear cell renal cell carcinoma (RCC) also is underway at Siteman Cancer Center.
The five-year study, for which Siteman Cancer Center is the only location in the bistate region, will evaluate the use of a novel pharmacologic, belzutifan, in combination with pembrolizumab to treat locally advanced RCC. A previous groundbreaking study, KEYNOTE-564, found that there was substantial benefit in the use of pembrolizumab (Keytruda) on its own as an adjuvant therapy. However, some high-risk patients did not respond well to pembrolizumab. An estimated 40 percent of patients will have a recurrence and develop metastatic disease.
Belzutifan (Welireg) targets a specific protein, the hypoxia-inducible factor 2 alpha protein (HIF-2α), that has been found to influence the growth of some cancers. It was approved by the FDA in 2021 after research found that the drug blocked or slowed the growth of cancerous tumors in patients diagnosed with a rare genetic disorder called von Hippel-Lindau (VHL) disease.
“We’re now evaluating the combination of the two drugs in all clear cell kidney cancers,” says Melissa Reimers, MD, site principal investigator for the clinical trial at Siteman. “We never had adjuvant therapies available to this patient population before the approval of pembrolizumab and now we have a promising combination treatment to offer high-risk patients who have already undergone surgery to remove their kidney.”
Clear cell RCC comprises an estimated 70 percent of all kidney cancers in adults. Dr. Reimers says the latest clinical trial, which will enroll 1,600 patients globally, began last March. Those eligible for the trial must be considered at high risk for recurrence and be enrolled within 12 weeks after undergoing surgery. They will be followed in the study for approximately one year. Adds Dr. Reimers, “We’re hoping to see that the disease-free survival benefit from both drugs translates into a superior treatment option, which could mean the establishment of a new standard of care.”
To view the list of active clinical trials at Siteman, go to siteman.wustl.edu/clinical-trials.