The DOI matches its Crossref record.
Phase Ib study of MIW815 (ADU-S100) in combination with spartalizumab (PDR001) in patients (pts) with advanced/metastatic solid tumors or lymphomas.
Abstract
2507 Background: MIW815 (ADU-S100) is a novel synthetic cyclic dinucleotide that activates the STimulator of INterferon Genes (STING) pathway impacting tumor cells, tumor microenvironment, vasculature, tumor-associated fibroblasts, and priming APC and CD8+ T cells. Spartalizumab is a humanized IgG4 mAb that blocks the binding of PD-1 to PD-L1/2. Preclinical data support synergistic antitumor effects when MIW815 (ADU-S100) is combined with checkpoint inhibitors. Methods: In this Phase Ib dose escalation study, pts with advanced/metastatic solid tumors or lymphoma received MIW815 (ADU-S100) (intratumoral injections [50–800 µg] either weekly [3 weeks on/1 week off] or Q4W) and spartalizumab (400 mg IV Q4W). Injected and non-injected tumor biopsies were obtained at baseline and on treatment. Primary objectives are to determine safety and identify a dose/schedule for future studies. Preliminary activity, pharmacokinetics (PK), and pharmacodynamics (PD) are also being explored. Results: As of Jan 11, 2019, 66 pts (median age: 61 y) with various solid tumors or lymphomas have been treated. Treatment was discontinued in 49 pts (74%) due to disease progression (n = 28), pt/physician decision (n = 18), AE (n = 2), or death (n = 1). No DLTs were reported during the first cycle at any dose level. Most common (≥5 pts) treatment-related AEs (TRAEs) were injection site pain (12%), pyrexia (11%), and diarrhea (9%). Grade 3/4 TRAEs (in ≥2 pts) were increased AST and ALT (3% each). Serious TRAEs were pyrexia (3%), increased amylase, increased lipase, diarrhea, fatigue, hyperthyroidism, partial seizures, dyspnea, and pneumonitis (all 2%). Partial responses in pts with PD-1–naive TNBC and PD-1–relapsed/refractory melanoma have been observed. MIW815 (ADU-S100) plasma exposure generally increased in a dose-dependent manner with a rapid terminal half-life. Response data, PK and PD analyses will be presented. Conclusions: Thus far, MIW815 (ADU-S100) + spartalizumab has demonstrated antitumor activity in PD-1–naive TNBC and PD-1–relapsed/refractory melanoma. The combination is well tolerated, with no DLTs reported to date. The MTD has not been reached and dose escalation is ongoing. Clinical trial information: NCT03172936.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The preliminary data showed that some combination therapies (e.g. ADU-S100 plus spartalizumab, MK-1454 plus pembrolizumab, manganese plus α-PD-1) had encouraging antitumor activity with a tolerable safety profile [270, 275, 276].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [275]
Citations
Cited by
Sorted by citations
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445
“ADU-S100 plus spartalizumab, MK-1454 plus pembrolizumab, manganese plus α-PD-1) had encouraging antitumor activity with a tolerable safety profile [270, 275, 276].”
BackgroundSun, X., Zhang, Y., Li, J., Park, K. S., Han, K., Zhou, X., Xu, Y., Nam, J., Xu, J., Shi, X., et al. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00962-9 · Cited by 808
Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges
Martin, J. D., Cabral, H., Stylianopoulos, T., & Jain, R. K. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0308-z · Cited by 691
The cGAS–STING pathway and cancer
Samson, N., & Ablasser, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00468-w · Cited by 740
Roles of natural killer cells in immunity to cancer, and applications to immunotherapy
Wolf, N. K., Kissiov, D. U., & Raulet, D. H. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00732-1 · Cited by 622
Intratumoural administration and tumour tissue targeting of cancer immunotherapies
Melero, I., Álvarez, E. C., Álvarez, M., Champiat, S., & Marabelle, A. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00507-y · Cited by 505
Cornel, A. M., Mimpen, I. L., & Nierkens, S. (2020) · Cancers · doi:10.3390/cancers12071760 · Cited by 501
STING Agonists as Cancer Therapeutics
Amouzegar, A., Chelvanambi, M., Filderman, J. N., Storkus, W. J., & Luke, J. J. (2021) · Cancers · doi:10.3390/cancers13112695 · Cited by 419
“The preliminary results of the phase Ib study on ADU-S100/MIW815 in combination with anti-PD1 spartalizumab in patients with advanced/metastatic solid tumors or lymphoma was presented at ASCO 2019 [73].”
BackgroundSelf-citationImmune evasion in cancer: mechanisms and cutting-edge therapeutic approaches
Tufail, M., Jiang, C., & Li, N. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02280-1 · Cited by 454
Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy
Garland, K. M., Sheehy, T. L., & Wilson, J. T. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00750 · Cited by 372
Development of Immunotherapy Combination Strategies in Cancer
Yap, T. A., Parkes, E. E., Peng, W., Moyers, J. T., Curran, M. A., & Tawbi, H. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1209 · Cited by 352
“Initial studies of intratumoral STING agonists have also demonstrated the ability of these agents to activate local immune responses and synergize with anti-PD-1 therapy (112,113), although mixed results from trials to date have demonstrated the need for patient selection for these approaches, and further pre-clinical…”
BackgroundProlonged activation of innate immune pathways by a polyvalent STING agonist
Li, S., Luo, M., Wang, Z., Feng, Q., Wilhelm, J., Wang, X., Li, W., Wang, J., Cholka, A., Fu, Y., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00675-9 · Cited by 327
Type I interferon-mediated tumor immunity and its role in immunotherapy
Yu, R., Zhu, B., & Chen, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04219-z · Cited by 309
“SD-101 Pembrolizumab Metastatic Melanoma or Recurrent or Metastatic HNSCC NCT02521870 1/2 Terminated [126] Pembrolizumab Hormone-Naïve Oligometastatic Prostate Cancer NCT03007732 2 Recruiting Nivolumab or Ipilimumab Metastatic Uveal Melanoma NCT04935229 1 Recruiting Nivolumab Chemotherapy-Refractory Metastatic Pancrea…”
BackgroundMechanisms of MHC-I Downregulation and Role in Immunotherapy Response
Taylor, B. C., & Balko, J. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.844866 · Cited by 326
“org 6 cell lung cancer and neuroblastoma (105, 106)Also, the EGFR family member, HER2, was shown to be inversely correlated with MHC-I expression in breast cancer and impairs T cell recognition of peptide: MHC-I complexes (107, 108).”
BackgroundTrial watch: STING agonists in cancer therapy
Le Naour, J., Zitvogel, L., Galluzzi, L., Vacchelli, E., & Kroemer, G. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1777624 · Cited by 289
NK cells mediate clearance of CD8 + T cell–resistant tumors in response to STING agonists
Nicolai, C. J., Wolf, N., Chang, I.-C., Kirn, G., Marcus, A., Ndubaku, C. O., McWhirter, S. M., & Raulet, D. H. (2020) · Science Immunology · doi:10.1126/sciimmunol.aaz2738 · Cited by 268
“The efficacy of PD-1 blockade in Hodgkin’s lymphoma (6) may possibly be due to the activity of NK cells, given that NK cells express functional PD-1 in mouse tumor models (50).”
ResultInfluentialChallenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy
Aval, L. M., Pease, J. E., Sharma, R., & Pinato, D. J. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9103323 · Cited by 253
“2% were serious (grade 3/4) and included increased lipase levels, diarrhoea and worsened liver function [108].”
BackgroundTrial watch: TLR3 agonists in cancer therapy
Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G., & Vacchelli, E. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1771143 · Cited by 239
ZnS@BSA Nanoclusters Potentiate Efficacy of Cancer Immunotherapy
Cen, D., Ge, Q., Xie, C., Zheng, Q., Guo, J., Zhang, Y., Wang, Y., Li, X., Gu, Z., & Cai, X. (2021) · Advanced Materials · doi:10.1002/adma.202104037 · Cited by 229
Martin, C. J., Datta, A., Littlefield, C., Kalra, A., Chapron, C., Wawersik, S., Dagbay, K. B., Brueckner, C. T., Nikiforov, A., Danehy, F. T., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay8456 · Cited by 224
Yang, K., Han, W., Jiang, X., Piffkó, A., Bugno, J., Han, C., Li, S., Liang, H. L., Xu, Z., Zheng, W., et al. (2022) · Nature Nanotechnology · doi:10.1038/s41565-022-01225-x · Cited by 224
The interactions between cGAS-STING pathway and pathogens
Cheng, Z., Dai, T., He, X., Zhang, Z., Xie, F., Wang, S., Zhang, L., & Zhou, F. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0198-7 · Cited by 216
“Two phase I clinical trials with STING agonists (ADUS100 and MK1454) have received good feedback, showing that dose escalation was tolerated and that CD8 T-cell infiltration in tumours was evident.(161,162) However, both STING agonists showed maximum efficacy only when delivered intratumourally, which might limit thei…”
BackgroundHuman Anti-tumor Immunity: Insights from Immunotherapy Clinical Trials
Egen, J. G., Ouyang, W., & Wu, L. C. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.010 · Cited by 198
Intratumoral Immunotherapy for Early-stage Solid Tumors
Hong, W. X., Haebe, S., Lee, A. S., Westphalen, C. B., Norton, J. A., Jiang, W., & Levy, R. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3642 · Cited by 184
“The intratumorally administered STING agonist ADU-S100 has demonstrated antitumor activity in PD-1–naive advanced triple-negative breast cancer and PD-1–refractory melanoma when administered in conjunction with checkpoint inhibitor spartalizumab (26).”
BackgroundDendritic cell maturation in cancer
Moon, C. Y., Belabed, M., Park, M. D., Mattiuz, R., Puleston, D. J., & Mérad, M. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00787-3 · Cited by 189
“Despite such challenges, STING agonists have shown initially encouraging results in combination with immunotherapy in clinical trials 362,363 .”
ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance
Jang, S. C., Economides, K. D., Moniz, R. J., Sia, C. L., Lewis, N. D., McCoy, C., Zi, T., Zhang, K. X., Harrison, R. A., Lim, J. Y. H., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02004-5 · Cited by 173
Self-citationDosta, P., Cryer, A. M., Dion, M. Z., Shiraishi, T., Langston, S., Lok, D. P. P., Wang, J., Harrison, S., Hatten, T., Ganno, M. L., et al. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01447-7 · Cited by 179
“However, drug delivery challenges, including rapid clearance from the TME, poor cell internalization and systemic toxicity, have limited CDN efficacy in preclinical and clinical trials 17,18 .”
BackgroundSTING suppresses bone cancer pain via immune and neuronal modulation
Wang, K., Donnelly, C. R., Jiang, C., Liao, Y., Luo, X., Tao, X., Bang, S., McGinnis, A., Lee, M. S., Hilton, M. J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24867-2 · Cited by 140
Li, J., Ren, H., Qiu, Q., Yang, X., Zhang, J., Zhang, C., Sun, B., Lovell, J. F., & Zhang, Y. (2022) · ACS Nano · doi:10.1021/acsnano.2c06926 · Cited by 131
Immunotherapy for Non-small Cell Lung Cancer: Current Landscape and Future Perspectives
Lim, S. M., Hong, M. H., & Kim, H. R. (2020) · Immune Network · doi:10.4110/in.2020.20.e10 · Cited by 123
“5%), and increase in CD8+ T cells in tumor after drug injection was suggested as a pharmacodynamics marker, reflecting therapeutic benefit (37).”
BackgroundTargeting Innate Immunity in Cancer Therapy
Rameshbabu, S., Labadie, B. W., Argulian, A., & Patnaik, A. (2021) · Vaccines · doi:10.3390/vaccines9020138 · Cited by 121
“ADU-S100/MIW815 is being investigated in phase II clinical trials in combination with ICI as a first line treatment for HNSCC [NCT03937141] [117].”
MethodTurning tumors from cold to inflamed to improve immunotherapy response
Gerard, C. L., Delyon, J., Wicky, A. M., Homicskó, K., Cuendet, M. A., & Michielin, O. A. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102227 · Cited by 118
Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors
Ouyang, P., Wang, L., Wu, J., Tian, Y., Chen, C., Li, D., Yao, Z., Chen, R., Xiang, G., Gong, J., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1344272 · Cited by 123
Wang, B., Yu, W., Jiang, H., Meng, X., Tang, D., & Liu, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1485546 · Cited by 119
From Design to Clinic: Engineered Nanobiomaterials for Immune Normalization Therapy of Cancer
Saeed, M., Chen, F., Ye, J., Shi, Y., Lammers, T., Geest, B. G. D., Xu, Z. P., & Yu, H. (2021) · Advanced Materials · doi:10.1002/adma.202008094 · Cited by 102
Kim, D., Endo, A., Fang, F. G., Huang, K., Bao, X., Choi, H.-W., Majumder, U., Shen, Y., Mathieu, S. R., Zhu, X., et al. (2021) · ChemMedChem · doi:10.1002/cmdc.202100068 · Cited by 108
Nucleic Acid Sensors as Therapeutic Targets for Human Disease
McWhirter, S. M., & Jefferies, C. A. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.004 · Cited by 91
Type I IFN activating type I dendritic cells for antitumor immunity
Liang, Y., Hannan, R., & Fu, Y.-X. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2564 · Cited by 91
Activation of Tumor-Cell STING Primes NK-Cell Therapy
Knelson, E. H., Ivanova, E. V., Tarannum, M., Campisi, M., Lizotte, P. H., Booker, M. A., Ozgenc, I., Noureddine, M., Meisenheimer, B., Chen, M., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0017 · Cited by 88
Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade
Peranzoni, E., Ingangi, V., Masetto, E., Pinton, L., & Marigo, I. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01590 · Cited by 85
“Moreover, the well-tolerated combination of intratumoral MIW815/ADU-S100 with the anti-PD-1 Spartalizumab has demonstrated antitumor activity in breast cancer and relapsed melanoma (164).”
BackgroundHuang, C., Shao, N., Huang, Y., Chen, J., Wang, D., Hu, G., Zhang, H., Luo, L., & Xiao, Z. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100839 · Cited by 88
“Besides, Rp, Rp-20, 30-c -di-AMPSS (ADU-S100), the synthetic phosphorothioate analog, was also widely investigated and has been approved in several clinical trials for cancer immunotherapy [75 – 77].”
MethodKong, X., Zuo, H., Huang, H., Zhang, Q., Chen, J., He, C., & Hu, Y. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.05.006 · Cited by 84
Lifting the innate immune barriers to antitumor immunity
Rothlin, C. V., & Ghosh, S. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000695 · Cited by 83
Luo, T., Nash, G. T., Jiang, X., Feng, X., Mao, J., Liu, J., Juloori, A., Pearson, A. T., & Lin, W. (2022) · Advanced Materials · doi:10.1002/adma.202110588 · Cited by 81
Chen, Y., Xu, L., Tang, T.-W., Chen, C.-H., Zheng, Q.-H., Liu, T., Mou, C., Wu, C.-H., & Wu, S. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c16728 · Cited by 78
Ying, X., Chen, Q., Yang, Y., Wu, Z., Zeng, W., Miao, C., Huang, Q., & Ai, K. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02186-6 · Cited by 87
Agonists and Inhibitors of the cGAS-STING Pathway
Yu, X., Cai, L., Yao, J., Li, C., & Wang, X. (2024) · Molecules · doi:10.3390/molecules29133121 · Cited by 76
Buss, C. G., & Bhatia, S. N. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2001569117 · Cited by 68
The Evolution of STING Signaling and Its Involvement in Cancer
Vashi, N., & Bakhoum, S. F. W. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.12.010 · Cited by 72
Gajewski, T. F., & Higgs, E. F. (2020) · Science · doi:10.1126/science.abc6622 · Cited by 68
Activation of Stimulation of Interferon Genes (STING) Signal and Cancer Immunotherapy
Luo, K.-W., Li, N., Ye, W., Gao, H., Luo, X., & Cheng, B. (2022) · Molecules · doi:10.3390/molecules27144638 · Cited by 68
“Ib clinical trial (NCT03172936) to characterize the safety and scientific validity of the combination in patients diagnosed with advanced/metastatic solid tumors or lymphomas [60].”
BackgroundRitter, J., Zhu, Z., Thai, T. C., Mahadevan, N. R., Mertins, P., Knelson, E. H., Piel, B. P., Han, S., Jaffe, J. D., Carr, S. A., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1310 · Cited by 60
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript STING agonism promotes T-cell recruitment, supporting the idea that targeting STING agonists to PTEN null TNBCs also promotes immunogenicity.”
BackgroundInfluentialXi, Q., Wang, M., Jia, W., Yang, M., Hu, J., Jin, J., Chen, X., Yin, D., & Wang, X. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01567 · Cited by 67
Landscape and perspectives of macrophage -targeted cancer therapy in clinical trials
Wang, S., Yang, Y., Ma, P., Huang, H., Tang, Q., Miao, H., Fang, Y., Jiang, N., Li, Y., Zhu, Q., et al. (2022) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2022.02.019 · Cited by 58
“Preliminary data from this ongoing study shows that ADUS100 is well tolerated and a partial response was observed.(57) To date, other clinical trials of STING agonists, including MK-1454, SB11285, GSK3745417, BMS-986301, and BISTING, have been approved by agencies.”
MethodSTING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications
Xu, C., Dobson, H. E., Yu, M., Gong, W., Sun, X., Park, K. S., Kennedy, A., Zhou, X., Xu, J., Xu, Y., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.03.036 · Cited by 53
Immunotherapies targeting stimulatory pathways and beyond
Marin-Acevedo, J. A., Kimbrough, E. O., Manochakian, R., Zhao, Y., & Lou, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01085-3 · Cited by 52
“Preliminary results for 66 patients with a median age of 61 years were published in an abstract [88].”
BackgroundInfluentialTherapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
Trojaniello, C., Luke, J. J., & Ascierto, P. A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.670726 · Cited by 53
Self-citationCurrent strategies for intratumoural immunotherapy – Beyond immune checkpoint inhibition
Yuan, J. D., Khilnani, A. D., Brody, J., Andtbacka, R. H. I., Hu‐Lieskovan, S., Luke, J. J., Diab, A. K., Marabelle, A., Snyder, A., Cao, Z. A., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.08.004 · Cited by 50
Self-citationEgan, G., Khan, D. H., Lee, J. B., Mirali, S., Zhang, L., & Schimmer, A. D. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1227 · Cited by 52
“Notably, ongoing clinical trials investigating the effect of the STING agonists ADU-S100 and MK-1454 in combination with PD-1/PD-L1 blockade show preliminary but encouraging outcomes in patients with solid tumors and lymphomas (95, 96).”
BackgroundcGAS/STING: novel perspectives of the classic pathway
Gao, M., He, Y., Tang, H., Chen, X., Liu, S., & Tao, Y. (2020) · Molecular Biomedicine · doi:10.1186/s43556-020-00006-z · Cited by 50
“Antitumor effects of ADU-S100 have been observed in PD-1–naive TNBC and PD-1–relapsed/ refractory melanoma [155, 156].”
BackgroundTherapeutic Development by Targeting the cGAS-STING Pathway in Autoimmune Disease and Cancer
Li, Q., Tian, S., Liang, J., Fan, J., Lai, J., & Chen, Q. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.779425 · Cited by 47
“reported that in comparison to cGAMP, ADU-S100 shows better metabolic stability and higher effectivity in activating STING (Meric-Bernstam et al., 2019).”
ResultPantelidou, C., Jadhav, H., Kothari, A., Liu, R., Wulf, G. M., Guerriero, J. L., & Shapiro, G. I. (2022) · npj Breast Cancer · doi:10.1038/s41523-022-00471-5 · Cited by 53
Qu, C. F., Shao, X., Jia, R., Song, G., Shi, D., Wang, H., Wang, J., & An, H. (2024) · ACS Nano · doi:10.1021/acsnano.4c05483 · Cited by 49
IFNγ Signaling in Natural and Therapy-Induced Antitumor Responses
Martínez, A., Arenas, E. J., & Arribas, J. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-3226 · Cited by 47
Unlocking the promise of systemic STING agonist for cancer immunotherapy
Sun, X., Zhou, X., Lei, Y. L., & Moon, J. J. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.03.047 · Cited by 48
“Because of these features, the first generation of STING agonists failed to generate significant clinical benefits [5,7] .”
BackgroundCrystal structures of human ENPP1 in apo and bound forms
Dennis, M. L., Newman, J. M., Dolezal, O., Hattarki, M. K., Surjadi, R. N., Nuttall, S. D., Pham, T. M., Nebl, T., Camerino, M. A., Khoo, P. S., et al. (2020) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798320010505 · Cited by 49
“ADU-S100 is a STING agonist that is currently in clinical trials (Meric-Bernstam et al., 2019), while QPS2 and Ex54 are published ENPP1 inhibitors.”
BackgroundSong, Z., Wang, X., Zhang, Y., Gu, W., Shen, A., Ding, C., Han, L., Xiao, R., Geng, M., Xie, Z., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01900 · Cited by 54
Wolf, N. K., Blaj, C., Picton, L. K., Snyder, G., Zhang, L., Nicolai, C. J., Ndubaku, C. O., McWhirter, S. M., García, K. C., & Raulet, D. H. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2200568119 · Cited by 46
“At the same time, early-phase clinical trials of STING agonists in patients have not yielded sustained clinical remissions (33, 34), indicating a need for improvements in this immunotherapy approach.”
BackgroundMethodShi, F., Su, J., Wang, J., Liu, Z., & Wang, T. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03967-5 · Cited by 44
SHR1032, a novel STING agonist, stimulates anti-tumor immunity and directly induces AML apoptosis
Song, C., Liu, D., Liu, S., Li, D., Horecny, I., Zhang, X., Li, P., Chen, L., Miller, M., Chowdhury, R., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-12449-1 · Cited by 43
Huang, Y., Nahar, S., Alam, M. M., Hu, S., McVicar, D. W., & Yang, D. (2023) · ACS Nano · doi:10.1021/acsnano.3c03195 · Cited by 43
Li, H., Zhang, C., Chen, Y., Xu, Y., Yao, W., & Fan, W. (2024) · ACS Nano · doi:10.1021/acsnano.4c08463 · Cited by 43
Immunomodulatory metal-based biomaterials for cancer immunotherapy
Yuan, K., Zhang, C., Pan, X., Hu, B., Zhang, J., & Yang, G. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.09.008 · Cited by 40
Advances in polymer nanomaterials targeting cGAS-STING pathway for enhanced cancer immunotherapy
Peng, S., Hou, X., Liu, J., & Huang, F. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.02.056 · Cited by 39
The clinical and molecular significance associated with STING signaling in breast cancer
Parkes, E. E., Humphries, M. P., Gilmore, E. S., Sidi, F. A., Bingham, V., Phyu, S. M., Craig, S. G., Graham, C., Miller, J. J., Griffin, D., et al. (2021) · npj Breast Cancer · doi:10.1038/s41523-021-00283-z · Cited by 37
Update of early phase clinical trials in cancer immunotherapy
Lee, D. H. (2021) · BMB Reports · doi:10.5483/bmbrep.2021.54.1.242 · Cited by 37
“ADU-S100 (MIW815) in combination with spartalizumab showed 2 PRs out of 66 patients treated (104).”
BackgroundIf small molecules immunotherapy comes, can the prime be far behind?
Zhang, J., Zhang, Y., Qu, B., Yang, H., Hu, S., & Dong, X. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113356 · Cited by 40
Zhang, G., Wang, N., Ma, Y., Zhai, S., Ngai, T., Ni, S., Jiang, X., Jiao, J., & Cui, J. (2024) · BMEMat · doi:10.1002/bmm2.12077 · Cited by 41
Jiang, X., Luo, T., Yang, K., Lee, M. J., Liu, J., Tillman, L., Zhen, W., Weichselbaum, R. R., & Lin, W. (2024) · Science Advances · doi:10.1126/sciadv.ado0082 · Cited by 34
“Systemic delivery of CDN-based STING agonists is limited by their poor PK and instability in plasma ( 34 , 58 – 60 ).”
Type I interferons in pancreatic cancer and development of new therapeutic approaches
Blaauboer, A., Sideras, K., van Eijck, C. H. J., & Hofland, L. J. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.103204 · Cited by 30
Zhu, C., Jiang, L., Yao, M., & Fang, C. (2021) · BMC Oral Health · doi:10.1186/s12903-021-01813-8 · Cited by 31
Lee, D., Huntoon, K. M., Wang, Y., Kang, M., Lü, Y., Jeong, S. D., Link, T. M., Gallup, T. D., Qie, Y., Li, X., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01194-7 · Cited by 32
Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy
Cho, W., Won, S., Choi, Y., Yi, S., Park, J. B., Park, J., Kim, C. E., Narayana, C., Kim, J. H., Yim, J., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202300978 · Cited by 30
Milling, L. E., Garafola, D., Agarwal, Y., Wu, S., Thomas, A., Donahue, N. D., Adams, J., Thai, N., Suh, H., & Irvine, D. J. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0247 · Cited by 29
“However, early clinical trials of STING agonists combined with PD-1 blockade, as well as combinations of tumortargeted IL2 and checkpoint blockade, have already proven to be safe, with few dose-limiting toxicities (44, 51).”
Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?
Passiglia, F., Reale, M. L., Cetoretta, V., & Novello, S. (2021) · ImmunoTargets and Therapy · doi:10.2147/itt.s253581 · Cited by 27
Vaccinating against cancer: getting to prime time
Chang, R., Gulley, J. L., & Fong, L. H. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006628 · Cited by 28
Second messenger 2′3′-cyclic GMP–AMP (2′3′-cGAMP): Synthesis, transmission, and degradation
Su, M., Zheng, J., Gan, L., Zhao, Y., Fu, Y., & Chen, Q. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114934 · Cited by 28
Lipid Nanoparticles Delivering Constitutively Active STING mRNA to Stimulate Antitumor Immunity
Liu, W., Alameh, M., Yang, J. F., Xu, J. R., Lin, P. J. C., Tam, Y. K., Weissman, D., & You, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314504 · Cited by 33
“STING agonists are being actively pursued as new cancer immunotherapies [31,36,37,99], but few have generated positive clinical outcomes [34,35].”
BackgroundIntratumoural immunotherapies in oncology
Xu, W., Atkinson, V. G., & Menzies, A. M. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2019.12.007 · Cited by 26
Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy
Meng, Y., Huang, J., Ding, J., Zhou, H., Li, Y., & Zhou, W. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101018 · Cited by 25
Liu, L., Fu, S., Gu, H., Li, Y., Zhu, G., Ai, H., & Li, W. (2025) · ACS Nano · doi:10.1021/acsnano.4c15115 · Cited by 26
Immune Modulation in Lung Cancer: Current Concepts and Future Strategies
Gaissmaier, L., & Christopoulos, P. (2020) · Respiration · doi:10.1159/000510385 · Cited by 24
Treatment Options for Advanced Melanoma After Anti-PD-1 Therapy
Babacan, N. A., & Eroglu, Z. (2020) · Current Oncology Reports · doi:10.1007/s11912-020-0894-z · Cited by 24
Innate Immune Activation with Multifunctional Nanoparticles for Cancer Immunotherapy
Jiang, X., & Lin, W. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202423280 · Cited by 29
Levy, E. S., Chang, R., Zamecnik, C. R., Dhariwala, M. O., Fong, L. H., & Desai, T. A. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00984 · Cited by 23
Ding, C., Du, M., Xiong, Z., Wang, X., Li, H., He, E., Han, L., Dang, Y., Lü, Q., Li, S., et al. (2023) · Chemical Science · doi:10.1039/d3sc01896b · Cited by 23
STING Activation and its Application in Immuno-Oncology
Lian, Y., Duffy, K. J., & Yang, J. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666191010155903 · Cited by 20
Engineering cGAS-agonistic oligonucleotides as therapeutics for cancer immunotherapy
Zhou, S., Su, T., Cheng, F., Cole, J., Liu, X., Zhang, B., Alam, S., Liu, J., & Zhu, G. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102126 · Cited by 24
Fang, J., Feng, L., Meng, L., Wang, X., Liu, H., Huang, L., Zhang, D., Li, J., Zhuang, R., Guo, Z., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05959-7 · Cited by 19
“Although STING agonists have been promising for cancer immunotherapy in clinical trials [10, 32], STING status is crucial for the efficacy of this therapy.”
BackgroundHuang, L., Lu, W., Wu, R., Li, Y., Ou, Z., Chen, J., Liu, Y., Wang, Y., Xue, W., Mu, P., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102251 · Cited by 20
Metadata
- Authors
- Meric-Bernstam, F., Sandhu, S. K., Hamid, O., Spreafico, A., Kasper, S., Dummer, R., Shimizu, T., Steeghs, N., Lewis, N., Talluto, C. C., Dolan, S., Bean, A., Brown, R., Trujillo, D., Nair, N., & Luke, J. J.
- Affiliations
- Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX;
- The University of Melbourne (AU)
- Angeles Clinic and Research Institute (US)
- Princess Margaret Cancer Centre (CA)
- Essen University Hospital (DE)
- University of Zurich (CH)
- National Cancer Center Hospital (JP)
- The Netherlands Cancer Institute (NL)
- Novartis Pharmaceuticals Corporation, East Hanover, NJ;
- Novartis Institutes for BioMedical Research, Cambridge, MA;
- Aduro BioTech (United States) (US)
- University of Chicago (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2019-05-20
- Volume
- 37
- Issue
- 15_suppl
- Pages
- 2507-2507
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2947265946
- Cited by
- 190
- References
- 0
- Citations by year
- 2026: 14 · 2025: 30 · 2024: 21 · 2023: 17 · 2022: 28 · 2021: 49 · 2020: 27 · 2019: 4
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- ADU-S100, spartalizumab, cyclic dinucleotides, STING pathway, PD-1/PD-L1 blockade, combination immunotherapy, advanced solid tumors, lymphoma, dose escalation, treatment-related adverse events, pharmacokinetics, pharmacodynamics, triple-negative breast cancer, melanoma, dose-limiting toxicity, intratumoral injection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
