Data from a Phase 1 trial of a multitargeled recombinant adenovirus 5 (Ad5) vaccine platform showed safety, T-cell immunogenicity, and clinical activity in patients with castration-resistant metastatic cancer, ImmunityBio, Inc., an immunity programmer, reported. .
The second-generation human Ad5 (hAd5) immunotherapy vaccine, which targets prostate-associated antigen (TAA) antigen (PSA), MUC-1 and brachyury, showed immune activation in 17 evaluated patients, with all participants mounting a T-cell response in at least 1 TAA.
“Finding of T-cell-mediated immunity caused in 100% of 17 [patients with prostate cancer] whose white blood cells were evaluated in the study confirms the ability of our hAd5 vaccine platform to generate a strong response to delivered antigens, ”said Patrick Soon-Shiong, Ph.D. med., founder and CEO of ImmunityBio, in a press release. “Furthermore, the demonstration that the vaccine can be administered multiple times, without adverse effects at a dose of 5 × 1011 virus particles, supports the use of this hAd5 platform in both cancer and infectious diseases such as COVID-19. These early results, which include signals of clinical activity and persistent stable disease, are encouraging for patients with highly resistant advanced metastatic prostate cancer and call for further research. “
In the study, adult patients with radiological evidence of progression or PSA progression were included to receive 3 vaccines simultaneously, each targeted at 3 TAAs, every 3 weeks for a maximum of 3 doses in the dose descaling arm. Those treated in the extension dose arm also received a starting vaccine every 8 weeks for 1 year. The primary endpoint of the study was safety determination and the recommended phase 2 dose.
One patient achieved a partial response to therapy, and five had stable disease for more than 6 months with a confirmed decline in PSA. The median progression-free survival was 22 weeks (95% CI, 19.1–34.0), and the median overall survival (OS) was not achieved. After 12 months the OS rate was 83.3% (95% CI, 56.8% -94.3%).
The vaccine had a tolerable safety profile and no degree greater than 3 treatment-related adverse reactions or dose-limiting toxicity was reported. It should be noted that 3 patients who achieved a response to PSA also had palliative radiotherapy. The researchers concluded that the efficacy of the vaccine would require further verification and its immunogenicity in combination with immuno-oncology and / or palliative radiation therapy was guaranteed.
The viral vector hAd5 is also used to develop vaccines for the potential treatment of other solid tumors, including breast, pancreatic, lung and head and neck cancers. Vaccines have shown their ability to overcome previous immunity to adenovirus in preclinical models.
1. Bilušić M, McMahon S, Madan RA and others. Phase I study of a multitarized recombinant Ad5 PSA / MUC-1 / brachyrium-based immunotherapy vaccine in patients with castration-resistant metastatic cancer (mCRPC). J Immune cancer. 2021; 9 (3): e002374. doi: 10.1136 / jitc-2021-002374
2. ImmunityBio predicts a 12-month overall survival probability of 83% in the NCI-led phase 1 study of a multi-target hAd5 immunotherapeutic vaccine in patients with advanced metastatic prostate cancer. News. ImmunityBio, Inc. March 29, 2021. Accessed April 5, 2021. https://www.businesswire.com/news/home/20210329005220/en