Current treatment options for stage D0 prostate cancer, in which a patient’s prostate specific antigen (PSA) level has become detectable again or has begun to increase after primary treatment, include watchful waiting, salvage radiation, and androgen deprivation therapy (ADT) — which often entails side effects that impact the quality of life.
But a new vaccine may one day delay the need to use ADT by harnessing patients’ immune systems, researchers reported at the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer, or SITC 2019, which occurred in Maryland in November 2019.1
The vaccine, which is currently being investigated at the National Institutes of Health’s National Cancer Institute, targets TARP, a 58-amino acid protein that is expressed in about 95% of prostate cancers. Initial research that looked at an earlier version of the vaccine showed that it was safe to use and that it decreased the rate of rise in PSA.2
Researchers are now recruiting participants for a randomized, placebo-controlled phase 2 trial with a target enrollment of 75 patients that will test the effectiveness of an improved version of the vaccine that can be used in a broader range of patients (ClinicalTrials.gov Identifier: NCT02362451). Results from the safety lead-in stage of the study have shown that the new version of the vaccine is also safe to use.1
“I find many of the participants on this trial say the same thing: The reason that they decide to come here is because they are not happy with the hormone therapy that’s often offered to them,” said the trial’s principal investigator Hoyoung Maeng, MD, assistant research physician at the vaccine branch of the National Cancer Institute’s Center for Cancer Research in Bethesda, Maryland. That’s because ADT is often associated with side effects such as low libido and low energy, she said.
Researchers at the Center had tested a first-generation TARP peptide-pulsed autologous dendritic cell vaccine in human subjects in a phase-1 clinical trial whose results were published in 2016 (ClinicalTrials.gov Identifier: NCT00972309).2 For that study, the authors recruited 41 men positive for HLA-A*0201 with stage D0 prostate cancer, to see whether administering the vaccine would decrease the rate of rise in PSA.
“What we found is that the vaccine reduced that slope or rate of rise,” said Jay Berzofsky, MD, PhD, chief of the vaccine branch in National Cancer Institute’s Center for Cancer Research in Bethesda, Maryland, who coauthored the study and is involved in the current trial. “Out of about 40 patients, 74% had a reduced slope at 1 year after starting vaccination.” The results also showed that the vaccine was safe to use.
For the ongoing trial, the researchers developed an improved version of the original TARP vaccine. In this new version, called the multiepitope (ME)-TARP dendritic cell vaccine, 5 overlapping 18-20-mer peptides that cover the full sequence of TARP have been added to the 2 peptides that were used in the first-generation TARP vaccine. The researchers added these 5 extra peptides to test that the vaccine works in patients with any HLA subtype, and not just those with the HLA-A*02 subtype, Dr Maeng explained.
So far, the researchers have completed the first stage of the trial, which involved testing the safety of the newer type of the vaccine in 6 patients. “We’ve treated the 6 lead-in patients and [have] shown that the broader vaccine with the 7 peptides is indeed safe,” Dr Berzofsky said. Moreover, consistent with the results of previous research, the researchers observed a decrease in PSA slope in 4 of the 6 patients, Dr Berzofsky said, but also cautioned that the number of patients studied was too small at that point to draw definitive conclusions.
The researchers are now enrolling patients for the randomized, placebo-controlled portion of the trial. Specifically, the investigators are recruiting men with stage D0 prostate cancer and PSA doubling time (PSADT) ranging from 3 to 15 months. Inclusion criteria also require that participants have completed — and recovered from — all prior definitive therapy for the primary tumor, such as surgery, brachytherapy, cryotherapy, radiotherapy, or another definitive-intent local therapy.
Participants will then be randomized in a 2:1 ratio to receive the new vaccine or placebo at weeks 3, 6, 9, 12, 15, and 24. The researchers aim to evaluate the PSA slope log change at 24 and 48 weeks.
If the vaccine is shown to work, it may help delay the use of ADT in such patients, Dr Maeng said. “If we can postpone the use of hormone therapy until we find a better shot for them, I think that’s significantly meaningful for those people who really don’t want to be on hormone therapy,” Dr Maeng said.
The researchers’ ultimate hope is to combine the vaccine with checkpoint inhibitors to treat the condition. Prostate cancer is considered to be immunologically “cold,” with very few T cells infiltrating the cancer, which in turn makes it a challenging malignancy to treat with immunotherapies.3 But the new vaccine may help induce a T-cell response, thus priming a tumor for this type of treatment. “We believe that the vaccine can convert a cold tumor into a hot tumor by inducing a T-cell response and make it amenable to therapy with checkpoint inhibitors,” Dr Berzofsky said.
Manish A. Vira, MD, vice chair for urologic research at Northwell Health’s Arthur Smith Institute for Urology, Lake Success, New York, who was not involved in the research, said that patients with stage D0 prostate cancer experience a rise in PSA levels even though there are no clear signs of the cancer spreading. “Currently in this stage, patients face the uncertain future of when prostate cancer may spread and [the] dilemma of when to start antihormonal therapy,” he said. “If successful, the vaccine can significantly prolong the time that patients can avoid the side effects of antitestosterone hormonal therapy. And perhaps more importantly, the vaccine may prime the immune system to continue to attack prostate cancer cells even in later stages of the disease.”
- Maeng HM, Wood LV, Steinberg S, et al. A randomized, placebo-controlled phase II study of multi-epitope TARP peptide autologous dendritic cell vaccination in men with stage D0 prostate cancer. Poster presented at: the 34th Annual Meeting & Preconference Programs (SITC 2019); November 6–10, 2019; National Harbor, MD. Abstract P460.
- Wood LV, Fojo A, Roberson BD, et al. TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with stage D0 prostate cancer. Oncoimmunology. 2016;5(8):e1197459.
- Cavallo J. How turning ‘cold’ tumors into ‘hot’ ones may improve response to immunotherapy. The ASCO Post. Published February 10, 2019. Accessed on December 2, 2019.