Abstract 924P
Background
Efficacy of anti-PD-1/PD-L1 therapy is attributed to the presence of infiltrating antigen-specific CD8+ T-cells. Despite the success of anti-PD-1/PD-L1 therapy, many pts present with immune desert or immune excluded tumors & only 13-16% of pts respond. Given this low response rate, it is imperative to combine agents which generate or expand anti-tumor T cells such as vaccines with anti-PD-1/PD-L1 therapies. This trial was launched with the objectives of evaluating safety/efficacy in pts that did not respond to anti-PD-1/PD-L1 therapy. SNS-301 is a first-in-class, bacteriophage-based immune activating agent targeting human aspartate β-hydroxylase (ASPH), a tumor associated antigen (TAA) overexpressed in 20+ tumor types. SNS-301 is a self-adjuvanted cancer vaccine consisting of λ-bacteriophage engineered to express an immunogenic fragment of ASPH fused to the phage gpD coat protein, shown to generate immune responses in a phase I study (NCT03120832).
Methods
Full eligibility criteria are described in NCT04034225. Pts are required to have ASPH+ SCCHN, actively receiving pembrolizumab or nivolumab for ≥12 weeks, & have a best response of stable disease (SD) or first evidence of progressive disease (PD). Pts provide a pre-SNS-301 tumor sample an on-treatment tumor biopsy, & an optional biopsy at PD to characterize the tumor microenvironment & correlate with clinical outcomes. SNS-301 with pembrolizumab is given until confirmed PD or unacceptable toxicity. Safety, tolerability, & anti-tumor activity such as objective response rate, duration of response, progression-free & overall survival, immune responses, tumor/immune biomarkers & associated treatment outcome.
Results
As of 18May20 6 pts have started treatment. All 18 screened pts were positive for ASPH. Adverse events were all Grade 1. Of 3 pts eligible for efficacy analysis, 2 pts have SD of 18+ weeks duration & 1 pt had PD. All pts had SD at enrollment (18-68 weeks). Correlative immunological analyses are ongoing & will be presented.
Conclusions
Early clinical data show that the combination of SNS-301 & pembrolizumab has manageable toxicity & capacity to achieve long-term disease stability with potential for responses after further treatment.
Clinical trial identification
NCT04034225; July 16, 2019.
Editorial acknowledgement
Legal entity responsible for the study
Sensei Biotherapeutics, Inc.
Funding
Sensei Biotherapeutics, Inc.
Disclosure
A.P. Algazi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Shareholder/Stockholder/Stock options: OncoSec; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Valitor Biosceinces; Honoraria (self), Advisory/Consultancy: Regeneron; Honoraria (self), Advisory/Consultancy: Array; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Dynavax; Research grant/Funding (institution): Genetech; Research grant/Funding (institution): Idera; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): ISA; Research grant/Funding (institution): LOXO; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Sensei Biotherapeutics; Research grant/Funding (institution): Tessa. T.J. Panella: Research grant/Funding (institution): Array; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Amgen; Non-remunerated activity/ies: ASCO. J. Celebi: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Sensei Biotherapeutics; Shareholder/Stockholder/Stock options: X4 Pharmaceuticals. I. Csiki: Leadership role, Shareholder/Stockholder/Stock options: Sensei Biotherapeutics. A. Drumheller: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Sensei Biotherapeutics; Shareholder/Stockholder/Stock options: Inovivo; Shareholder/Stockholder/Stock options: Allogene; Shareholder/Stockholder/Stock options: Merrimack. J. Campbell: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Sensei Biotherapeutics. R. Pierce: Leadership role, Research grant/Funding (self), Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment: Sensei Biotherapeutics; Research grant/Funding (institution): Juno; Research grant/Funding (institution): Exicure; Research grant/Funding (institution): Minerva Therapeutics; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): X4 Pharmaceuticals; Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (self), Research grant/Funding (institution): Pulse Biosciences; Research grant/Funding (self), Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Immunomic Therapeutics; Shareholder/Stockholder/Stock options: OncoSec Medical. W.B. Smith: Full/Part-time employment: NOCCR/VRG, An AMR Company, LLC. All other authors have declared no conflicts of interest.