Oliver Rosen, MD, CMO of SQZ Biotechnologies speaks about the ASCO 2021 Abstract – 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.
Link to Abstract:
https://meetinglibrary.asco.org/record/196015/abstract
Backstory:
T cell activation and cancer vaccination effectiveness are limited by ineffective MHC-I presentation of tumor antigens to CD8+ T cells. The Cell Squeeze technique pushes peripheral blood mononuclear cells (PBMCs) through a microfluidic chip, causing cell membrane rupture and cytosolic delivery of HPV16 E6 and E7 antigens. These antigen-presenting cells (APC) were not genetically modified and were matured with CpG7909. In preclinical studies, this method improved MHC-I presentation in human and mouse cells. When compared to previous vaccination modalities, m-SQZ-PBMC-HPV produced strong CD8+ T cell responses and enhanced anti-tumor effects in mouse tumor trials.
Methodologies:
Patients with incurable HPV16+ malignancies advancing despite unrestricted previous treatment, ECOG 0-1, acceptable organ function, and a biopsiable lesion were enrolled in the SQZ-PBMC-HPV-101 study. Manufacturing of the cryopreserved product took around 24 hours after leukapheresis at the research location, with a vein-to-vein period of about 1 week. Without a conditioning regimen, outpatient SQZ-PBMC-HPV was given IV every three weeks. Cohort 3 was the first to use double antigen priming (DP), which took place on Cycle 1 Days 1 and 2. The cell batch size dictated the maximum treatment period for each patient. RECIST 1.1 and iRECIST were used to evaluate the response. Pre- and post-treatment measurements of investigational biomarkers were taken.
Outcomes:
12 patients [anal (7), head and neck (3), and cervical (2)] were dosed in three groups (3 in 0.5 x10e6/kg, 5 in 2.5 x10e6/kg, and 4 in 2.5 x10e6/kg [DP]). The median number of previous treatments was four (range one to seven), and all but one patient was given checkpoint inhibitors (CPI); ten patients had liver or lung metastases. After freezing, all batches of SQZ-PBMC-HPV showed CD8 activation in vitro, and batch size had no effect on treatment duration at the dosage levels studied thus far. In the three cohorts, the median number of doses was 3 (3–10), 3 (2–4), and 3 (3–4), respectively. One participant (10 dosages) stayed in the trial for 42 weeks. Tx was well tolerated, with no DLTs, related Grade (G) >3 SAEs, or related G >3 AEs. One patient in cohort 1 had a G2 infusion response as well as cytokine release syndrome. In cohort 2, one patient was not evaluable for DLT. The best response was stable disease in four out of ten evaluable patients, according to RECIST 1.1. Preliminary tumor studies before and after SQZ infusion revealed enhanced immune activation in certain individuals.
Observations:
SQZ-PBMC-HPV-101 The Cell Squeeze technique has been shown to be clinically feasible, and modified APCs have been found to be tolerable. The research enables the assessment of modified APCs’ immunogenicity in people. Preliminary findings support testing in conjunction with CPI. Pre- and post-therapy biopsies and blood samples will be used to show efficacy, safety, and correlated biomarker data.
Clinical trial information: NCT04084951 –
http://clinicaltrials.gov/show/NCT04084951