Data from a phase 1 trial of a multitargeted recombinant adenovirus 5 (Ad5) vaccine platform demonstrated safety, T-cell immunogenicity, and clinical activity in patients with metastatic castration-resistance prostate cancer, reported the agent’s developer ImmunityBio, Inc. in a news release.
The second-generation human Ad5 (hAd5) immunotherapy vaccine targeting tumor-associated antigens (TAA) of prostate-specific antigen (PSA), MUC-1, and brachyury showed immune activation in 17 patients evaluated, with all participants mounting a T-cell response in at least 1 TAA.
“The finding of T-cell–mediated immunity induced in 100% of 17 [patients with prostate cancer] whose white blood cells were evaluated in the study validates the ability of our hAd5 vaccine platform to generate a potent response to antigens delivered,” Patrick Soon-Shiong, MD, Founder and Executive Chairman of ImmunityBio, said in a press release. “Furthermore, the demonstration that the vaccine can be administered repeatedly, without adverse effects at the dose of 5 × 1011 viral particles, supports the application of this hAd5 platform in both cancer and infectious diseases such as COVID-19. These early results, which include signals of clinical activity and durable stable disease, are encouraging for patients with highly resistant advanced metastatic prostate cancer and warrants further study.”
The trial enrolled adult patients with radiologic evidence of progression or PSA progression to receive 3 vaccines concurrently, each targeting the 3 TAAs, every 3 weeks for a maximum of 3 doses in the dose de-escalation arm. Those treated in the dose-expansion arm also received a booster vaccine every 8 weeks for 1 year. The primary end point of the trial was determining the safety and recommended phase 2 dose.
One patient achieved a partial response to therapy and 5 had stable disease for more than 6 months with confirmed PSA decline. The median progression-free survival was 22 weeks (95% CI, 19.1-34.0) and the median overall survival (OS) was not reached. At 12 months, the rate of OS was 83.3% (95% CI, 56.8%-94.3%).
The vaccine had a tolerable safety profile, with no grade greater than 3 treatment-related adverse events or dose-limiting toxicities noted. Of note, 3 patients who achieved PSA response also had palliative radiotherapy. The investigators concluded that the vaccine’s efficacy will require further validation and its immunogenicity in combination with immuno-oncology and/or palliative radiation therapy is warranted.
The hAd5 viral vector is also being used to develop vaccines to potentially treat other solid tumors including breast, pancreatic, lung, and head and neck cancers. The vaccines have shown their ability to overcome prior adenovirus immunity in preclinical models.
1. Bilusic M, McMahon S, Madan RA, et al. Phase I study of a multitargeted recombinant Ad5 PSA/MUC-1/brachyury-based immunotherapy vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC). J Immunother Cancer. 2021;9(3):e002374. doi: 10.1136/jitc-2021-002374
2. ImmunityBio Announces 12-Month Overall Survival Probability of 83% in NCI-Led Phase 1 Study of Multi-Targeted hAd5 Immunotherapy Vaccine in Patients with Advanced Metastatic Prostate Cancer. News release. ImmunityBio, Inc. March 29, 2021. Accessed April 5, 2021. https://www.businesswire.com/news/home/20210329005220/en