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T HIS STUDY IS CURRENTLY RECRUITING INTO P HASE 2. E MAIL EDEGOMA @ EXICURETX . COM IF YOU ARE INTERESTED IN PARTICIPATING AS AN INVESTIGATOR AST-008: A Novel Approach to TLR9 Agonism with PD-1 Blockade for Anti-PD-1 Refractory Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (CSCC) Mohammed M. Milhem 1 , Cesar A. Perez 2 , Glenn J. Hanna 3 , Trisha M. Wise-Draper 4 , Shailender Bhatia 5 , Alice S. Bexon 6 , Weston L. Daniel 7 , and Steven J. O’Day 8 1 University of Iowa Health Care, Iowa City, IA; 2 Sylvester Comprehensive Cancer Center at University of Miami, Miami, FL; 3 Dana-Farber Cancer Institute, Boston, MA; 4 University of Cincinnati Cancer Center, Cincinnati, OH; 5 University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA; 6 Bexon Clinical Consulting, Upper Montclair, NJ; 7 Exicure, Inc, Skokie, IL; 8 John Wayne Cancer Institute, Santa Monica, CA. Corresponding Author: Mohammed M. Milhem ([email protected]) B ACKGROUND K EY S TUDY D ESIGN E LEMENTS Open label, multicenter phase 1b/2 dose escalation/expansion design study in progress (NCT03684785) Phase 2s: Intratumoral (IT) AST-008 plus pembrolizumab or cemiplimab for PD- (L)1 resistant MCC and PD-1 resistant CSCC, respectively. Phase 1b enrolled all solid tumors. Key study design features: Safety • Dose escalation used a double dose limiting toxicity period (DLT) design. AST-008 dosed IT alone for 2 weeks, then the anti-PD-1 antibody is added. Efficient differential assessment of safety and tolerability of AST-008 and the combination • FDA allowed dose expansion cohort of AST-008 plus cemiplimab in CSCC after performing dose escalation with AST-008 plus pembrolizumab Key study design features: Efficacy • 2 or more RECIST 1.1-evaluable lesions required for enrollment. One lesion is to remain uninjected with AST-008 over the course of the study to observe abscopal effects Key study design features: Pharmacodynamics • Paired serial biopsies taken at baseline, after AST-008, and after combination. One lesion is injected with AST-008 over the course of the study, one is not (termed target and witness lesions). Enables differential assessment of local and distant effects of AST-008 and the combination AST-008 is a toll-like receptor 9 (TLR9) agonist in a spherical nucleic acid (SNA) format with potent immune-stimulatory properties AST-008, A NTI -PD-1 A NTIBODIES , AND THE C ANCER I MMUNITY C YCLE AST-008 DLT Period Combination DLT Period Pembrolizumab or Cemiplimab IV AST-008 IT Paired Biopsies Tumor Assessment AST-008 and anti-PD-1 pharmacodynamics are expected to synergize and propagate steps of the cancer immunity cycle (Cancer Res 2019;79(13 Suppl):abstract CT044) AST-008 SNAs are dense, radial arrangements of nucleic acids that have increased cellular uptake (below) and an optimal presentation of the oligonucleotides for TLR9 agonism vs free oligonucleotides Free Oligonucleotide SNA Abstract TPS3164

AST-008: A Novel Approach to TLR9 Agonism with PD-1 ...€¦ · AST-008 is a toll-like receptor 9 (TLR9) agonist in a spherical nucleic acid (SNA) format with potent immune-stimulatory

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  • THIS STUDY IS CURRENTLY RECRUITING INTO PHASE 2. EMAIL [email protected] IF YOU ARE INTERESTED IN PARTICIPATING

    AS AN INVESTIGATOR

    AST-008: A Novel Approach to TLR9 Agonism with PD-1 Blockade for Anti-PD-1 Refractory Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (CSCC) Mohammed M. Milhem1, Cesar A. Perez2, Glenn J. Hanna3, Trisha M. Wise-Draper4, Shailender Bhatia5, Alice S. Bexon6, Weston L. Daniel7, and Steven J. O’Day8 1University of Iowa Health Care, Iowa City, IA; 2Sylvester Comprehensive Cancer Center at University of Miami, Miami, FL; 3Dana-Farber Cancer Institute, Boston, MA; 4University of Cincinnati Cancer Center, Cincinnati, OH; 5University of Washington/Fred Hutchinson Cancer

    Research Center, Seattle, WA; 6Bexon Clinical Consulting, Upper Montclair, NJ; 7Exicure, Inc, Skokie, IL; 8John Wayne Cancer Institute, Santa Monica, CA. Corresponding Author: Mohammed M. Milhem ([email protected])

    BACKGROUND KEY STUDY DESIGN ELEMENTS

    Open label, multicenter phase 1b/2 dose escalation/expansion design study in progress (NCT03684785) Phase 2s: Intratumoral (IT) AST-008 plus pembrolizumab or cemiplimab for PD-(L)1 resistant MCC and PD-1 resistant CSCC, respectively. Phase 1b enrolled all solid tumors. Key study design features: Safety • Dose escalation used a double dose

    limiting toxicity period (DLT) design. AST-008 dosed IT alone for 2 weeks, then the anti-PD-1 antibody is added. Efficient differential assessment of safety and tolerability of AST-008 and the combination

    • FDA allowed dose expansion cohort of AST-008 plus cemiplimab in CSCC after performing dose escalation with AST-008 plus pembrolizumab

    Key study design features: Efficacy • 2 or more RECIST 1.1-evaluable

    lesions required for enrollment. One lesion is to remain uninjected with AST-008 over the course of the study to observe abscopal effects

    Key study design features: Pharmacodynamics • Paired serial biopsies taken at

    baseline, after AST-008, and after combination. One lesion is injected with AST-008 over the course of the study, one is not (termed target and witness lesions). Enables differential assessment of local and distant effects of AST-008 and the combination

    AST-008 is a toll-like receptor 9 (TLR9) agonist in a spherical nucleic acid (SNA) format with potent immune-stimulatory properties

    AST-008, ANTI-PD-1 ANTIBODIES, AND THE CANCER IMMUNITY CYCLE

    OBJECTIVES

    AST-008 DLT

    Period

    Combination

    DLT Period

    Pembrolizumab

    or Cemiplimab IV

    AST-008 IT Paired Biopsies

    Tumor Assessment

    AST-008 and anti-PD-1 pharmacodynamics are expected to synergize and propagate steps of the cancer immunity cycle (Cancer Res 2019;79(13 Suppl):abstract CT044)

    AST-008

    SNAs are dense, radial arrangements of nucleic acids that have increased cellular uptake (below) and an optimal presentation of the oligonucleotides for TLR9 agonism vs free oligonucleotides

    Free Oligonucleotide SNA

    Abstract TPS3164

    https://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.shorthttps://cancerres.aacrjournals.org/content/79/13_Supplement/CT044.short

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