Data from the ongoing Phase 1/2 clinical trial of SNS-301 in combination with pembrolizumab (Keytruda®; Merck & Co) is well tolerated in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).

The investigational agent, SNS-301, is a first-in-class self-adjuvanted bacteriophage-base immune-activating vaccine targeting human aspartate β-hydroxylase (ASPH), a tumor-associated antigen commonly overexpressed in cancer.

Bioengineered by scientists at Sensei Biotherapeutics, the inactivated bacteriophage virus expressing a fragment of ASPH as a fusion protein to the bacteriophage lambda capsid decoration protein, gpD, is specifically designed to overcome immune tolerance and induce robust and durable antigen-specific humoral and cellular responses.

ASPH is a transmembrane protein that hydroxylates aspartyl and asparaginyl residues of epidermal growth factor (EGF)-like protein domains and promotes cellular motility, migration, and adhesion. The agent is highly expressed during fetal development and in placental trophoblasts, but not in any other healthy adult human tissue. The expression of ASPH is uniquely upregulated in cancer cells and is reported to be overexpressed in over 20 different solid neoplasms, in which it propagates a malignant phenotype,

ASPH signaling is associated with increased cell proliferation, invasiveness, and poor prognosis and occurs through the Notch pathway and is implicated in the epithelial to mesenchymal transition (EMT).

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Clinical trial
The multi-center Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, and anti-tumor activity of SNS-301 in combination with pembrolizumab, as well as immune response and tumor/immune biomarkers.

The data will be presented as a poster (#6029) by Alain Algazi, M.D., from the University of California San Francisco to the medical community at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place virtually June 4 – 8, 2021.[1]

The study has two cohorts with a total of 60 patients with locally advanced unresectable or metastatic squamous cell carcinoma of the head and neck (SCCHN) who did not achieve a response to prior treatment with PD-1 blockade (Cohort A) or patients who did not receive prior therapy with PD-1 blockade (Cohort B).

Data cut-off-date
As of the April 14, 2021 cut-off date, 21 patients with locally advanced unresectable or metastatic SCCHN had been enrolled and treated in the study. Twenty of the patients enrolled did not achieve an objective response to prior treatment with PD-1 blockade (Cohort A) and one patient was PD-1 blockade naïve (Cohort B). The safety profile of SNS-301 in combination with pembrolizumab observed from 20 evaluable patients was favorable and consistent with previously reported data.

Efficacy data were available from twelve patients in Cohort A. Notably, the efficacy bar was set high by enrolling patients with no objective response to prior PD-1 blockade (median 7.5 months). Data from nine evaluable patients from Cohort A were last reported from this study at the Society for Immunotherapy of Cancer’s (SITC) 35th Annual Meeting.

“These data suggest SNS-301, when combined with PD-1 blockade, has the potential to provide long-term benefit as second and later line treatment for patients with late-stage cancer and few other treatment options,” explained Marie-Louise Fjallskog, M.D., Ph.D., Chief Medical Officer of Sensei Biotherapeutics.

“We expect to report more mature data, including data for SNS-301 combination therapy in the frontline setting, by the end of this year,” Fjallskog added.

“This study continues to enhance our understanding of the broad potential of our ImmunoPhage™ platform,” said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics.

“The information we are gathering is just one aspect of the potential of our ImmunoPhage platform to expand the durability and improve the treatment of many devastating cancers. Our team continues to lead advances in the understanding of bacteriophage through internal research and collaborations with world-class academic laboratories, and we are excited to apply these learnings to our pipeline of ImmunoPhage programs.”

Safety Data
As of the data cut-off, a safety analysis conducted in 20 evaluable patients showed that SNS-301 in combination with pembrolizumab continues to have a favorable safety profile.

The combination of SNS-301 and pembrolizumab was well tolerated. Mostly Grade 1-2, mild to moderate, unrelated adverse events (AE) were observed. Four Grade 3 AEs were reported as treatment-related: dehydration, pruritus, rash and EKG QT prolongation.

Efficacy Data
An analysis of anti-tumor activity was conducted in 12 patients who did not achieve an objective response to prior treatment with PD-1 blockade (Cohort A). No patients were evaluable from Cohort B as of the cut-off date.

The data confirmed that 67% (n=8/12) of patients achieved stable disease (SD) or partial response (PR). This included one patient with PD-L1 negative tumor who achieved a tumor reduction of 71% that is still ongoing after 11 months of therapy. Nanostring™ data for this patient show T-cell increase and T-cell activation. A total of seven patients achieved SD, including two patients with long-standing SD (8 and 10 months).

Patient outcomes appear to correlate to post-treatment PD-L1 expression and immune infiltration in tumors.

Analyses of secondary endpoints using ELISA and ELISPOT assays to evaluate SNS-301 specific B and T cell responses in patient samples are ongoing. Sensei expects to report these data as part of the larger dataset planned by the end of 2021. Sensei also plans to add a third cohort by the end of 2021 to evaluate SNS-301 with HPV-specific E6/E7 ImmunoPhage.

Clinical trials
Addition of SNS-301 to Checkpoint Inhibitor Treatment in Metastatic/Recurrent SCCHN – NCT04034225

Highlights of prescribing information
Pembrolizumab (Keytruda®; Merck & Co., Inc) [Prescribing Information]

Algazi AP, Shah D, Smith W, Panella TJ, Shin DM, Bruce JY, Melhem R, Campbell JS, Abell L, et al. Update on safety and efficacy of a phase 1/2 of SNS-301 added to pembrolizumab in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). Presented at: American Society of Clinical Oncology (ASCO) held June 4 – 8, 2021.[Abstract]

Featured image: Histopathologic image illustrating well-differentiated squamous cell carcinoma in the excisional biopsy specimen. Hematoxylin-eosin stain. Photo courtesy: © 2016 – 2021 KGH. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

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