4827 - Final Results from a Phase I Clinical Trial Evaluating the Safety, Immunogenicity, and Anti-Tumor Activity of SNS-301 in Men with Biochemically Relapsed Prostate Cancer

Background

SNS-301 (formerly PAN-301) is a first-in-class therapeutic vaccine candidate targeting human aspartyl (asparaginyl) β-hydroxylase (ASPH). ASPH is differentially over-expressed in multiple human cancers but not in healthy adult tissue and is associated with tumor cell growth, motility and invasiveness. SNS-301 is engineered to express an ASPH fusion product within an inactivated λ-bacteriophage viral vector. Previously presented pre-clinical data demonstrate the vaccine’s ability to overcome tumor self-tolerance and provide anti-tumor immuno-stimulatory effect.

Methods

SNS-301 was administered intradermally every 21 days to men with biochemically (PSA) relapsed prostate cancer with evidence of ASPH over-expression. A 3 + 3 dose-escalation design evaluated dose levels of 2X10¹⁰, 1X10¹¹, and 3X10¹¹ particles with the primary objectives of defining safety and identifying a recommended phase 2 dose (R2PD). Secondary endpoints included immunogenicity parameters and an assessment of anti-tumor activity.

Results

Twelve patients (pts.) with detectable levels of ASPH received 3-18 doses of SNS-301 (median = 10 doses). The vaccine was well tolerated with only 3 pts. experiencing an adverse event (AE) considered at least possibly related to study drug. All AEs were ≤ grade 3 and no dose-limiting toxicity was observed. All pts. experienced dose-dependent ASPH-specific immune responses incl. T-cell and antibody parameters. Specifically, post-treatment anti-ASPH antibody titers increased in a dose-dependent fashion from 3.0 (Day 1) to 4.6 (Day 2) to 12.0 (Day 3) units/ml. Anti-tumor activity was observed in 6/8 eligible pts. (75%) with declines noted in both overall PSA level and PSA doubling rate.

Conclusions

SNS-301 appears safe and well tolerated when administered intradermally at doses up to the RP2D of 3X10¹¹ particles. The vaccine induces vibrant antigen-specific immune responses and demonstrates provocative signals of anti-tumor activity. Based on these results, a multi-site phase 2 efficacy clinical trial will commence enrollment in the 2^nd half of 2018.

Clinical trial identification

NCT03120832.

Legal entity responsible for the study

Sensei Biotherapeutics, Inc. 620 Professional Drive Gaithersburg, MD 20879 USA.

Funding

Sensei Biotherapeutics, Inc. 620 Professional Drive Gaithersburg, MD 20879.

Editorial Acknowledgement

Disclosure

H. Ghanbari: Founder and employee: Drug sponsor and owns equity in the company. J.C. Oliver: Employee: Contract research organization who managed operational aspects of the clinical trial; Funding: Drug sponsor. A. Shahlaee: Employee: Drug sponsor. S. Fuller: Employee: Drug sponsor; Owns equity in the company. All other authors have declared no conflicts of interest.