Cancer Vaccine Elicits Promising Responses in Renal Cell Carcinoma

A personalized cancer vaccine showed promising results in a phase 1 trial, keeping all nine patients with RCC cancer-free for a median of 34.7 months.

In a recent clinical trial, all participating patients treated with a personalized cancer vaccine following the surgical removal of their tumors remained cancer-free at a median data cut-off of 34.7 months, or nearly three years.

“I think what was surprising was how well it worked, the fact that during the observation period, we didn't see any relapses, so that's very important,” said Dr. Catherine Wu, co-senior author of the phase 1 clinical trial findings published in Nature, in an interview with CURE.

Wu is chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber Cancer Institute, and institute member at the Broad Institute of MIT and Harvard, in Boston.

The study enrolled nine patients with stage 3 and 4 clear cell renal cell carcinoma, who experienced successful anti-cancer immune responses associated with the vaccine.

“This approach is truly distinct from vaccine attempts in kidney cancer,” stated Dr. David Braun in a news release issued by Dana-Farber Cancer Institute. “We pick targets that are unique to the cancer and different from any normal part of the body, so the immune system can be effectively 'steered' towards the cancer in a very specific way. We learned which specific targets in the cancer are most susceptible to immune attack and demonstrated that this approach can generate long-lasting immune responses, directing the immune system to recognize cancer. We believe this work can form a foundation for the development of neoantigen vaccines in kidney cancer.”

Braun, first author of the study, is formerly of Dana-Farber and Harvard Medical School, and now a medical oncologist and physician-scientist at Yale Cancer Center and Yale School of Medicine in New Haven, Connecticut.

“We were able to demonstrate that those responses against the components that we put in the vaccine also directly led to an immune response against the patient's own tumor cells,” Wu told CURE. “So, [it was] kind of closing the loop that we predicted on the tumor, we created something that we thought would hit the tumor, and then we were able to demonstrate that that's actually so.”

Notably, the most common adverse events were low-grade injection side reactions in all patients and transient flu-like symptoms in eight of nine patients, with no patients experiencing a grade 3 (severe) or higher (dose-limiting) toxicity, researchers stated in their findings.

Looking forward, the news release noted that clinical trials with larger numbers of patients are needed to confirm the efficacy of the vaccine well as explore its full potential, with an ongoing multicenter international randomized study using a similar personalized cancer vaccine set to be administered in combination with the immunotherapy Keytruda (pembrolizumab).

Now recruiting, the INTerpath-004 phase 2 clinical trial is expected to enroll approximately 272 patients with renal cell carcinoma and will compare treatment with the vaccine V940 plus Keytruda versus placebo plus Keytruda. The study has an estimated primary completion date of Aug. 1, 2028, and an estimated study completion date of June 8, 2032, according to its listing on clinicaltrials.gov.

“The academic, phase one trials are really to signal find and to see if there's any sort of modicum of activity,” Wu said. “The larger studies are really in the realm of support by industry [sources]. So, there are some industry-sponsored studies in this area that are looking to see if there [is a] signal. They'll be read out in the future. And if positive, I would anticipate that that would be practice changing.”

Reference:

“A neoantigen vaccine generates antitumour immunity in renal cell carcinoma” by Dr. David A. Braun et al., Nature.

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