# COMMANDER-001: Initial safety data from a phase I/II dose escalation/expansion study of SQZ-eAPC-HPV, a cell-based mRNA therapeutic cancer vaccine for HPV16+ solid tumors This page is a text version of a Portal Biotechnologies publication. The bibliographic record is labeled in the text so it can be read without the surrounding website. ## Bibliographic record - Title: COMMANDER-001: Initial safety data from a phase I/II dose escalation/expansion study of SQZ-eAPC-HPV, a cell-based mRNA therapeutic cancer vaccine for HPV16+ solid tumors - Document type: Poster - Year: 2022 - Outlet: ESMO I-O - Page URL: https://portal.bio/publications/2022-commander-001-initial-safety-data-from-a-phase-i-ii-dose-escalation-expansion-study-o--ajkGdhEAAC0Ac95t - Markdown URL: https://portal.bio/publications/2022-commander-001-initial-safety-data-from-a-phase-i-ii-dose-escalation-expansion-study-o--ajkGdhEAAC0Ac95t.md - Original file: https://portal-bio.cdn.prismic.io/portal-bio/65ccd1ca9be9a5b998b5d03a_SQZ_ESMO-IO-eAPC_Poster183_FINAL.pdf ## Summary Justin Moser, Meredith Pelster, Antonio Jimeno, Jong Chul Park, Wade T Iams, Trisha Wise-Draper, Julia Jennings, Nathan Miselis, Rui-Ru Ji, Scott Loughhead, Ricardo F Zwirtes, Marshelle S Warren, Armon Sharei, Howard Bernstein, and Michael S Gordon ## Publication text COMMANDER-001: Initial safety data from a phase I/II dose escalation/expansion study of SQZ-eAPC-HPV, a cell-based mRNA therapeutic cancer vaccine for HPV16+ solid tumors Justin Moser1, Meredith Pelster2, Antonio Jimeno3, Jong Chul Park4, Wade T Iams5, Trisha Wise-Draper6, Julia Jennings7, Nathan Miselis7, Rui-Ru Ji7, Scott Loughhead7, Ricardo F Zwirtes7, Marshelle S Warren7, Armon Sharei7, Howard Bernstein7, and Michael S Gordon1 HonorHealth Research and Innovation Institute (Scottsdale, AZ)1; Sarah Cannon Research Institute at Tennessee Oncology (Nashville, TN)2; University of Colorado Cancer Center (Aurora, CO)3; Massachusetts General Hospital (Boston, MA)4; Vanderbilt University Medical Center (Nashville, TN)5; University of Cincinnati Medical Center (Cincinnati, OH)6; SQZ Biotechnologies (Watertown, MA)7 Rationale & Background - SQZ-eAPC-HPV 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). Since SQZ-eAPC-HPV is HLA agnostic, the addressable patient population is estimated to be 2-3x greater than the SQZ-PBMC-HPV clinical candidate (Figure 1, Table 1). - SQZ-eAPC-HPV is engineered from peripheral blood mononuclear cells (PBMCs) 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 (Figure 2A). - 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 (Figure 2). Cohort 1 (n=4) Cohort 2 (n=1) Total (N=5) Median Age, years (min, max) 62.0 (45, 72) 70.0 (70, 70) 64.0 (45, 72) Female, n (%) 3 (75.0) 1 (100.0) 4 (80.0) Baseline ECOG PS of 1, n (%) 3 (75.0) 1 (100.0) 4 (80.0) RMH Score High, n (%) 2 (50.0) 1 (100.0) 3 (60.0) Diagnosis, n (%) Anal Cancer 0 (0.0) 1 (100.0) 1 (20.0) Cervical Cancer 2 (50.0) 0 (0.0) 2 (40.0) Head and Neck Cancer 1 (25.0) 0 (0.0) 1 (20.0) Vaginal Cancer 1 (25.0) 0 (0.0) 1 (20.0) Metastatic Disease, n (%) 4 (100.0) 1 (100.0) 5 (100.0) Median Number of Prior Lines, n (min, max) 3 (2, 5) 5 (5, 5) 4 (2, 5) Table 2: Patient Characteristics Figure 3: Leukapheresis to Administration Eligible patients undergo a single leukapheresis. During the manufacturing process, patient cells are processed in less than 24 hours to generate cryopreserved drug product. The leukapheresis to product release time for the 1st administration is approximately one week. Patients do not require a conditioning regimen before the 1st administration; SQZ-eAPC-HPV is administered outpatient after the first dose. Leukapheresis & Manufacturing Data Cohort 1 (n=4) Cohort 2 (n=1) Total ### (n=5) AE, Any Causality 3 (75.0) 1 (100.0) 4 (80.0) AEs Occurring in >1 Patient, Any Causality Fatigue 2 (50.0) 1 (100.0) 3 (60.0) Hypokalemia 2 (50.0) 0 (0.0) 2 (40.0) Related AE 1 (25.0) 1 (100.0) 2 (40.0) Fall 1 (25.0) 1 (0.0) 1 (20.0) Hypertension 0 (0.0) 1 (100.0) 1 (20.0) Related Grade 3+ AEs 0 (0.0) 1 (100.0)1 1 (20.0) Related Serious AEs 0 (0.0) 0 (0.0) 0 (0.0) AEs of Special Interest2 0 (0.0) 0 (0.0) 0 (0.0) Dose-Limiting Toxicity 0 (0.0) 0 (0.0) 0 (0.0) AEs leading to D/C 0 (0.0) 1 (100.0)3 1 (20.0) Fatal Related AEs 0 (0.0) 0 (0.0) 0 (0.0) Table 3: Safety Summary Cohort 1 was found to be safe and tolerable. The only related adverse events was a grade 1 fall. The one patient enrolled in Cohort 2 experienced grade 3 hypertension deemed possibly related to study drug; this patient entered the study with an ongoing medical history of hypertension. Before Cycle 2, Day 1 the patient developed grade 3 pneumonia and discontinued treatment with SQZ-eAPC-HPV. This patient is not evaluable for DLT. Safety Data & Tolerability Assessment Summary Presented at ESMO IO on 07-09Dec2022 · Acknowledgements: We thank the patients, their families, and their caregivers for their time and their willingness to participate in this study. We also thank the investigators and the investigational site staff for their contributions to the study. · Corresponding Author: Justin Moser (jmoser@honorhealth.com). Justin Moser has consulted for BMS, Amunix, Thirona Bio, Adagen and Imaging Endpoints, Boxer Capitol, and Oberland Capitol; receives research support from NovoCure, Genentech, Alpine Immune Sciences, Amgen, Trishula Therapeutics, BioEclipse Therapeutics, FujiFilm, ImmuneSensor, Simcah, Repertoire Immune Sciences, Nektar Therapeutics, Synthorx Inc, Istari Oncology, Ideaya Biosciences, Rubius, University of Arizona, Storm Therapeuitcs, Werewolf Therapeutics, and Fate Therapuetics; has received honoraria from Caris Life Sciences and TGen; serves as a Caris Molecular Tumor Board Member and Caris Consultant; and is a speaker for Caris Life Sciences and Immunocore. - Cell collection to product release was ~1 week (Table 1). One year’s worth of SQZ-eAPC-HPV, the maximum amount of drug able to be administered on study, was able to be manufactured for all patients in Cohort 1. - Four patients with HPV16+ solid tumors (cervical, 2; oropharyngeal, 1; vaginal, 1) were dosed in Cohort 1 (Table 2). - All patients completed the 28-day dose limiting toxicity (DLT) period without experiencing a DLT. No related serious adverse events were reported (Table 3). - Of the four patients enrolled in Cohort 1, 2 patients experienced a best overall response of stable disease (Figure 5). - One patient remains on treatment. Enrollment into Cohort 1 is complete. ### Results Patient Data (continued) - COMMANDER-001 (NCT05357898) is a two-part study. Part 1A assesses SQZ-eAPC-HPV as a monotherapy with intravenous dosing every 3 weeks (Q3W) (Figure 4). - Cohort 1 enrolled patients to receive 0.5 x 106 SQZ-eAPC-HPV cells/kg Q3W for up to 1 year or until available doses are exhausted. - Following Cycle 1 Day 1 SQZ-eAPC-HPV administration, patients undergo a 23 hours observation. Subsequent doses are administered in the outpatient setting. - Adverse events were assessed by CTCAEv5.0. Tumor response was assessed by RECIST1.1. Events suggestive of hypersensitivity and cytokine release syndrome were collected as adverse events of special interest. Experimental Design & Methods Figure 4: COMMANDER-001 Study Design Objectives Part 1A: SQZ-eAPC-HPV monotherapy will be tested with at least 3 different dose levels to identify the recommended phase 2 dose (RP2D). Additional higher or lower dose cohorts may be opened. Part 1B: SQZ-eAPC-HPV RP2D is tested in combination with 200mg pembrolizumab. Pembrolizumab will be given on cycle 1 day 8, then after SQZ-eAPC-HPV at every subsequent day 1. Part 2: SQZ-eAPC-HPV is given as a monotherapy for the first 2 cycles (lead-in), then SQZ-eAPC-HPV and pembrolizumab are given in combination. 1Grade 3 hypertension 2AESIs are events suggestive of hypersensitivity 3Grade 3 pneumonia - SQZ-eAPC-HPV explores the impact of multiplexed mRNA-based engineering of a cancer vaccine. It is thus far well tolerated. - While data are preliminary, a pronounced pharmacodynamic effect was seen in a patient with a prolonged stable disease. - Enrollment in Cohort 2 has commenced at a dose of 2.5 x 106 eAPC/kg. ### Conclusions Leukapheresis SQZ Process <24-hours QC and Batch Release Administration to Patient SQZ-PBMC-HPV SQZ-eAPC-HPV Differentiation Cell Type PBMC PBMC N/A Delivery material E6/E7 SLP E6, E7, CD86, mbIL-2, and mbIL-12 mRNA More epitopes, duration of presentation, signal 2&3 Maturation 4 hr CpG incubation None More yield and shorter process time Anticipated T cell response HLA-A*02 restricted CD8+ T cell response HLA agnostic CD8+ T cell response. Potential for CD4 T cell response Broader, better stimulated T cell response across HLA types Sites of Priming Spleen and lymph Nodes Spleen and lymph nodes N/A Median Manufacturing Time 17.1 hours 12.8 hours Shorter manufacturing time due to the removal of the CpG incubation Median Viability 91% 94% SQZ-eAPC-HPV has demonstrated improved viability Figure 1: A. Since SQZ-eAPC-HPV is not HLA restricted, it is expected to have an addressable patient population 2-3x greater than SQZ-PBMC-HPV. B. Initial screening data from COMMANDER-001 compared to SQZ-PBMC-HPV-101 is in line with these increased addressable patient population. BA Addressable Patient Population (%) ### Sqz-pbmc - ### Hpv SQZ-eAPC- ### Hpv 24.4% 73.9% 1.7% ### Sqz-pbmc-hpv-101 Enrolled Screen Fail In Screening 55.6%33.3% 11.1% ### Commander-001 Enrolled Screen Fail In Screening Table 1: SQZ-eAPC-HPV is an enhanced SQZ® clinical therapeutic candidate. Efficacy and Preliminary Pharmacodynamic Data ### A B Patient Data Figure 5: Positive ELISpot Response in Patient with Stable Disease A. Samples were collected for testing in an IFNɣ ELISpot for E6 and E7 reactivity at every visit. Patient 2 demonstrated the highest reactivity of any patient. Shown is the best E7 ELISpot response from patient 2, which occurred at C5D1. B. In patient 2, this E7 positive response correlated with persistent stable disease per RECIST 1.1. C. Summary table of best overall response and best E6/E7 ELISpot reactivity for all patients. Patient Maximum SFU per 106 PBMCs (above background) Negative Cut-off value (SFU per 106 PBMCs) Timepoint at maximal response Best Overall Response per ### Recist 1.1 Cohort 1 1 66 70 C3D1 Stable Disease 2 848 60 C5D1 Stable Disease 3 20 60 C1D8 Progressive Disease 4 231 60 C2D8 Progressive Disease Cohort 2 5 N/A N/A N/A Not Evaluated A C SFU = spot forming unit; IFNɣ ELISpot performed on non-expanded cells; minimal background detected Figure 2: Administration and Mechanism of Action A. PBMCs are collected from the patient and squeezed with mRNA resulting in SQZeAPC-HPV. After administration SQZeAPC-HPV cells then migrate to the lymphoid organs where they are designed to activate CD8 T cells. B. The mRNAs are expected to be translated resulting in signal 1, 2, and 3 activation and ultimately activation of HPV16 specific CD8 cells. Part 1: Monotherapy Phase (1a) and Combination Phase (1b) Recurrent or metastatic HPV-16+ cancer HLA agnostic ICI-naïve patients (≤1 prior lines) Recurrent or metastatic HPV-16+ cancer HLA agnostic Platinum experienced CPI experience/offered SQZ-eAPC-HPV RP2D q3w + Pembrolizumab 200 mg q3w Part 2: Lead-in Phase (Requires DSMB approval) SQZ-eAPC-HPV RP2D q3w 6w n=3 to 12 BOIN SQZ-eAPC-HPV 2.5 x106/kg q3w SQZ-eAPC-HPV 5.0 x106/kg q3w SQZ-eAPC-HPV RP2D q3w + Pembrolizumab 200 mg q3w n=6 to 12 BOIN Safety and Tolerability Feasibility Efficacy (ORR) Biomarkers SQZ-eAPC-HPV 0.5 x106/kg q3w SQZ-eAPC-HPV RP2D-1 q3w + Pembrolizumab 200 mg q3w n=6 to 12 BOIN Dose de-escalation if DLT >30% Safety and Tolerability Feasibility Efficacy (ORR) Biomarkers Enrolling Cohorts Objectives i ii i: ELISpot vehicle control ii: C5D1 ELISpot response COMMANDER-001 Patient ELISpot Summary Data i ii Maximal SFU per 106 PBMC B Patient 2 Swimlane ### Fpn: 183p ## Provenance Some publications reference SQZ Biotechnologies, a company Dr. Armon Sharei and colleagues previously founded. Portal is the next generation company leveraging Dr. Sharei's platform technology.