Abstract 191P
Background
Cancer vaccines strive to produce robust, antigen-targeted, T cell-mediated anti-tumor responses, but have struggled to induce tumor regression in patients. The Cell Squeeze® system achieves efficient antigen presentation by delivering target antigens directly into the cytosol of a patient’s PBMCs. SQZ-PBMC-HPV is an autologous cell vaccine that presents epitopes of HPV16 viral oncoproteins on HLA-A*02 to induce CD8 T cell activation. Monotherapy data showed tumor inflammation markers that may indicate correlation with clinical response motivating expansion of the monotherapy and combination with immune checkpoint inhibitors (ICIs).
Methods
SQZ-PBMC-HPV-101 enrolls patients (pts) with advanced HPV16+ cancers who have progressed after standard therapy, have an ECOG 0-1, adequate organ function, and measurable lesion(s) per RECIST1.1. Manufacturing of the cell product takes <24 hours with a collection-to-release time of about 1 week. The RP2D dose of SQZ-PBMC-HPV is 5x106 live cells/kg double prime, given IV q3w. Pts also receiving atezolizumab or ipilimumab are dosed IV q3w. Blood samples and paired biopsies are collected for pharmacodynamic (PD) analyses.
Results
As of Aug 17, 2022, 14 pts have been treated at the RP2D +/- ICI [head and neck (10), cervical (2), vulvar (1), and anal (1)]. These pts have received a median of 3 prior lines of systemic cancer therapy. Treatment was well-tolerated with no dose limiting toxicities, Grade (G) >2 related SAEs, related G >3 AEs, or cytokine release syndrome. In addition to assessment by RECIST1.1 criteria, 8 pts in the monotherapy cohort provided paired tumor biopsies for assessment of changes in the tumor microenvironment including CD8 influx, Treg presence, antigen expression, and evasion mechanisms (MHCI and PD-L1). This report will be the first to summarize the PD and safety endpoints for pts receiving SQZ-PBMC-HPV + ICI therapy.
Conclusions
Building on encouraging earlier monotherapy response data with SQZ-PBMC-HPV, this monotherapy and ICI combination data will further elucidate the impact of this therapeutic vaccine’s mechanism and evaluate its place in patient treatment.
Clinical trial identification
NCT04084951.
Legal entity responsible for the study
SQZ Biotechnologies Company.
Funding
SQZ Biotechnologies Company.
Disclosure
A. Jimeno: NCI R01CA149456, R01DE024371, and P50CA261605. AJ institution has contracts with Cantargia, DebioPharm, Iovance, Khar Biopharma, Merck, Moderna, Pfizer, Sanofi, and SQZ for trials where he is the local PI N.R. Miselis: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies; Financial Interests, Personal, Stocks/Shares: SQZ Biotechnologies, Merck & Co, BMS, Iovance, Abbott, Quest Diagnostics, Baxter International. J.C. Park: JCP reports honoraria from Cancer Expert Now and Alira Health; consulting or advisory roles with GC Cells, Selexcine, ABL Bio, BW Biomed, and Mitoimmune; and institutional contracts with ALX Oncology, Inhibrx, Merck, Oncorus, ISA Therapeutics, and Monopteros Therapeutics. J. Jennings: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. N. Dhani: Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies; Financial Interests, Personal, Full or part-time Employment: Princess Margaret Cancer Centre. U. Holtick: Honoraria & Consultancies BMS/ Celgene, Kite/ Gilead, GlaxoSmithKline, Janssen-Cilag, Miltenyi Biotec, Novartis, Pfizer, Sanofi. W.T. Iams: WTI reports support from an NCCN Young Investigator Award, consulting relationships with Genentech, Jazz Pharma, G1 Therapeutics, Mirati, Bristol Myers Squibb, Takeda, Janssen, EMD Serono, OncLive, Curio Science, Chardan, Cello Health, Outcomes Insights, and Clinical Care Options. WTI - Vanderbilt University Medical Center has contracts with Takeda, Amgen, Nitto Biopharma, Lilly, and Merck for trials where he is the local PI. N. Nair: Non-Financial Interests, Institutional, Advisory Role: SQZ Biotechnologies; Financial Interests, Personal, Full or part-time Employment: Roche. M. Kornacker: Non-Financial Interests, Institutional, Advisory Role: SQZ Biotechnologies; Financial Interests, Personal, Full or part-time Employment: Roche. S.M. Loughhead: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. Named inventor of patents either licensed by or assigned to SQZ Biotechnologies. H. Bernstein: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. Named inventor of patents either licensed by or assigned to SQZ Biotechnologies and SQZ officer. R. Zwirtes: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. R.R. Ji: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. M. Warren: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. SQZ officer. A. Sharei: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. Named inventor of patents either licensed by or assigned to SQZ Biotechnologies; SQZ officer.