Abstract 183P
Background
SQZ-eAPC-HPV (eAPC) is an autologous, cell based, HLA-genotype agnostic HPV therapeutic cancer vaccine that leverages clinical and manufacturing experience from the SQZ-PBMC-HPV clinical candidate (NCT04084951). eAPC is engineered from peripheral blood mononuclear cells by using Cell Squeeze® technology to simultaneously deliver 5 mRNAs encoding for full length HPV16 E6 and E7 proteins, CD86, and membrane-bound (mb) IL-2 and mbIL-12 cytokines. By driving co-localized MHC-I antigen presentation (E6/E7), costimulation (CD86), and cytokine signaling (IL-2/IL-12), the eAPCs may enable more potent T cell activation and proliferation while limiting known toxicity of interleukin therapy.
Methods
Part 1A assesses eAPC as a monotherapy with intravenous dosing every 3 weeks (Q3W). In Cohort 1 enrolled patients (pts) receive 0.5 x 106eAPC/kg Q3W for up to 1 year. Following a Bayesian optimal interval design, 3 - 12 pts may be enrolled per cohort. Eligible pts undergo a single leukapheresis. Preconditioning is not required and eAPCs are administered outpatient after the first dose. Adverse events were assessed by CTCAEv5.0. Tumor response was assessed by RECIST1.1. Baseline and on-treatment pharmacokinetic and pharmacodynamic samples were also collected.
Results
4 pts with HPV16+ solid tumors (cervical, 2; oropharyngeal, 1; vaginal, 1) were dosed in Cohort 1. Cell collection to product release was ∼1 week; adequate eAPC doses were manufactured for all pts. All pts completed the 28-day dose limiting toxicity (DLT) period without experiencing a DLT. No related serious adverse events were reported. Only one eAPC related treatment emergent adverse event was reported (Grade 1 fall). Enrollment in Cohort 2 has commenced at a dose of 2.5 x 106 eAPC/kg. The presentation may include safety, preliminary efficacy, and pharmacokinetic/pharmacodynamic data from a cut-off proximal to presentation.
Conclusions
eAPC explores the impact of multiplexed mRNA-based engineering of a cancer vaccine. As of the data cut-off for this abstract (17Aug22), it is thus far well tolerated.
Clinical trial identification
NCT05357898.
Legal entity responsible for the study
SQZ Biotechnologies Company.
Funding
SQZ Biotechnologies Company.
Disclosure
J. Moser: Financial Interests, Institutional, Advisory Role: BMS, Amunix, Thirona Bio, Adagen, Imaging Endpoints, Caris; Financial Interests, Institutional, Funding: NovoCure (Inst), Genentech (Inst), Alpine Immune Sciences (Inst), Amgen (Inst), Trishula Therapeutics (Inst), BioEclipse Therapeutics (Inst), FujiFilm (Inst), ImmuneSensor (Inst), Simcah (Inst), Repertiore Immune Sciences (Inst), Nektar Therapeutics (Inst), Synthorax Inc (Inst), Istari Oncology (Inst), Ideaya Biosciences (Inst), Rubius (Inst), University of Arizona (Inst); Financial Interests, Institutional, Other, Honoraria: Caris Life Sciences, TGen; Financial Interests, Institutional, Member: Caris Molecular Tumor Board; Financial Interests, Institutional, Invited Speaker: Caris Life Sciences, Immunocore. M. Pelster: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Bayer, Novartis, Astellas, CytomX, Gritstone Oncology, Arcus Biosciences, Surface Oncology, Codiak BioSciences, Immune-Onc Therapeutics, HiberCell; Financial Interests, Institutional, Principal Investigator: SQZ Biotechnologies. A. Jimeno: Financial Interests, Institutional, Funding, for 3 trials: NCI; Financial Interests, Institutional, Principal Investigator: Cantargia, DebioPharm, Iovance, Khar Biopharma, Merck, Moderna, Pfizer, Sanofi, SQZ Biotechnologies. J.C. Park: Financial Interests, Institutional, Other, Honoraria: Cancer Expert Now, Alira Health; Financial Interests, Institutional, Advisory Role: GC Calls, Selexcine, ABL Bio, MitoImmune; Financial Interests, Institutional, Advisory Board: BW Biomed; Financial Interests, Institutional, Funding: ALX Oncology (Inst), SQZ Biotech (Inst), Inhibrx (Inst), Merck (Inst), Oncorus (Inst), ISA Therapeutics (Inst), Monopteros Therapeutics (Inst). W.T. Iams: Financial Interests, Institutional, Funding, Young Investigator Award: NCCN; Financial Interests, Institutional, Advisory Role: Genentech, Jazz Pharma, G1 Therapeutics, Mirati, BMS, Takeda, Janssen, EMD Serono, OncLive, Curio Science, Chardan, Cello Health, Outcomes Insights, Clinical Care Options; Financial Interests, Institutional, Principal Investigator: Takeda, Amgen, Nitto Biopharma, Lilly, Merck, SQZ Biotechnologies. T. Wise-Draper: Financial Interests, Institutional, Stocks/Shares, Stocks and Other Ownership Interests: High Enroll; Financial Interests, Institutional, Other, Honoraria: Physician Education Resource; Financial Interests, Institutional, Advisory Role: Shattuck Labs, Rakuten, Exicure, Merck, Caris Life Sciences; Financial Interests, Institutional, Funding: Merck, Caris Life Sciences, AstraZeneca/MedImune, Bristol Myers Squibb, GlaxoSmithKline, GSK, Janssen Oncology; Financial Interests, Institutional, Other, travel, accomodations: Merck, Caris Life Sciences; Financial Interests, Institutional, Other, travel, accomodations, expenses: AstraZeneca/MedImune, Bristol Myers Squibb, Bexion, Lilly, Tesaro. J. Jennings: Financial Interests, Institutional, Full or part-time Employment: SQZ Biotechnologies. N.R. Miselis: Financial Interests, Institutional, Full or part-time Employment: SQZ Biotechnologies. R.R. Ji: Financial Interests, Institutional, Full or part-time Employment: SQZ Biotechnologies. S.M. Loughhead: Financial Interests, Institutional, Full or part-time Employment: SQZ Biotechnologies; Financial Interests, Institutional, Other, Named inventor of patents either licensed by or assigned to SQZ Biotechnologies: SQZ Biotechnologies. R. Zwirtes: Financial Interests, Institutional, Full or part-time Employment: SQZ Biotechnologies. M. Warren: Financial Interests, Institutional, Officer: SQZ Biotechnologies. A. Sharei: Financial Interests, Institutional, Officer: SQZ Biotechnologies; Financial Interests, Institutional, Other, Named inventor of patents either licensed by or assigned to SQZ Biotechnologies: SQZ Biotechnologies. H. Bernstein: Financial Interests, Institutional, Officer: SQZ Biotechnologies; Financial Interests, Institutional, Other, Named inventor of patents either licensed by or assigned to SQZ Biotechnologies: SQZ Biotechnologies. M. Gordon: Financial Interests, Institutional, Advisory Role: Imaging Endpoints, Instil Bio, Tracon, Daiichi, Qualigen; Financial Interests, Institutional, Other, Patents planned, issued, or pending: Caremission; Financial Interests, Institutional, Funding: GSK, AbbVie, Merck Serono, MedImmune, Incyte, Pfizer, Amgen, Gilead Sciences, Endocyte, Seattle Genetics, Plexxicon/Daiichi, Celldex, Tracon, Deciphera, Fujifilm, Minnemarita, Nektar, Novita, Biosplice, Corcept, Novartis, Toray, Genzada, Salarius, Agenus, Inhibrx, AADi, Revolution Medicine, Blueprint, Astellas, BioNTech, Helix, IgM Biosciences, ImmuneSensor, Bioeclipse, Bioline, Black Diamond, Codiak, Dracen, Elevation Oncology, Framewave, Forma Therapeutics, IntraImmun SG, Pionyr, Trishula, Tolero, Vedanta Biosciences, Coordination Therapeutics, Ideaya Biosciences, I-Mab, NiKang, Nimbus Therapeutics, OncoResponse, Riboscience, Rubius Therapeutics, Simcha Therapeutics, Siranomics, Synthorx, Theseus Pharmaceuticals, Zai Labs, Genentech/Roche.