Initial results of a first-in-human, dose escalation study of a cell-based vaccine in HLA A*02+ patients (pts) with recurrent, locally advanced or metastatic HPV16+ solid tumors: SQZ-PBMC-HPV-101.
Authors: Jimeno Antonio , Baranda Joaquina Celebre , Mita Monica M. , Gordon Michael S. , Taylor Matthew H. , Iams Wade Thomas , Janku Filip , Matulonis Ursula A. , Bernstein Howard , Loughhead Scott , Kornacker Martin , Zwirtes Ricardo F. , Rosen Oliver , Eng Cathy 
Published: June 2021

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Background: Ineffective MHC-I presentation of tumor antigens to CD8+ T cells limits T cell activation and the efficacy of cancer vaccines. The Cell Squeeze technology drives peripheral blood mononuclear cells (PBMCs) through a microfluidic chip leading to temporary cell membrane disruption and delivery of HPV16 E6 and E7 antigens cytosolically. These antigen presenting cells (APC) were matured with CpG7909 and were not genetically modified. Preclinically, this approach showed improvement in MHC-I presentation for human and murine cells. In murine tumor studies, m-SQZ-PBMC-HPV elicited robust CD8+ T cell responses and improved anti-tumor effects when compared to other vaccine modalities. Methods: SQZ-PBMC-HPV-101 included pts with incurable HPV16+ cancers progressing after unlimited prior therapy, ECOG 0-1, adequate organ function and a biopsiable lesion. After leukapheresis at the study site, manufacturing of the cryopreserved product took < 24 hours with a vein-to-vein time of approx. 1 week. Out-patient SQZ-PBMC-HPV was given IV q 3 weeks without a conditioning regimen. Double antigen priming (DP) was introduced with Cohort 3 and occurred on Cycle 1 Days 1 and 2. Maximum treatment duration for each patient was determined by the cell batch size. Response was assessed via RECIST 1.1 and iRECIST. Investigational biomarkers were measured pre- and post-treatment. Results: 12 pts [anal (7), head and neck (3), and cervical (2)] were dosed in 3 cohorts (3 pts in 0.5 x10e6/kg, 5 pts in 2.5 x10e6/kg, and 4 pts in 2.5x 10e6/kg [DP]). Median lines of prior Tx were 4 (range 1 - 7) and all but one pt were pretreated with checkpoint inhibitors (CPI); 10 pts had liver or lung metastases. All batches of SQZ-PBMC-HPV demonstrated CD8 activation in vitro after thawing, and batch size did not limit therapy duration at dose levels tested to date. Median number of doses were 3 (3 - 10), 3 (2 - 4), and 3 (3 – 4) in the 3 cohorts, respectively. One pt (10 doses) remained on study for 42 weeks. Tx was well-tolerated and there were no DLTs, Grade (G) >3 related SAEs or related G >3 AEs. One pt in cohort 1 experienced both a G2 infusion-related reaction and cytokine release syndrome. One pt in cohort 2 was not evaluable for DLT. Four out of 10 evaluable pts had stable disease per RECIST 1.1 as the best response. Preliminary tumor analyses pre- and post-therapy indicated increased immune activity in some patients after SQZ infusion. Conclusions: SQZ-PBMC-HPV-101 demonstrated clinical feasibility of the Cell Squeeze technology and favorable tolerability of engineered APCs. The study allows for the characterization of the immunogenicity of engineered APCs in humans. Preliminary results warrant the testing in combination with CPI. Efficacy, safety, and correlative biomarker data will be presented, from pre- and post-therapy biopsies and blood samples. Clinical trial information: NCT04084951.