^
    1m
    PEMDA-HN: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (clinicaltrials.gov)
    P2, N=81, Recruiting, Flamingo Therapeutics NV | Trial completion date: Aug 2025 --> May 2026 | Trial primary completion date: Sep 2024 --> May 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • danvatirsen (AZD9150)
    2ms
    AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and in Patients With Non-Small-Cell Lung Cancer (clinicaltrials.gov)
    P1, N=76, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Jun 2024
    Trial completion date • Combination therapy • Metastases
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • danvatirsen (AZD9150)
    3ms
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=175, Active, not recruiting, AstraZeneca | Trial completion date: May 2023 --> Mar 2026
    Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • ALK fusion
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • rilvegostomig (AZD2936) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    3ms
    NCI-2018-01296: Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer (clinicaltrials.gov)
    P2, N=39, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025
    Trial completion date • Trial primary completion date • Mismatch repair • IO biomarker • Metastases
    |
    CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    3ms
    Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. (PubMed, Nat Med)
    A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.
    P2 data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    STK11 (Serine/threonine kinase 11) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STK11 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • danvatirsen (AZD9150)
    4ms
    Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck (clinicaltrials.gov)
    P1/2, N=340, Active, not recruiting, AstraZeneca | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2023 --> Mar 2025
    Phase classification • Trial completion date • Combination therapy • Metastases
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab) • AZD5069 • danvatirsen (AZD9150)
    5ms
    BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P1, N=156, Active, not recruiting, AstraZeneca | Phase classification: P1b --> P1 | Trial completion date: Sep 2023 --> Jun 2024
    Phase classification • Trial completion date
    |
    HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • FGFR (Fibroblast Growth Factor Receptor) • CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
    |
    PD-L1 expression • FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)
    6ms
    Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Montefiore Medical Center | Trial completion date: Dec 2027 --> Mar 2028 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Mar 2025 --> Jun 2025
    Trial completion date • Trial initiation date • Trial primary completion date
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • danvatirsen (AZD9150)
    6ms
    PEMDA-HN: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (clinicaltrials.gov)
    P2, N=81, Recruiting, Flamingo Therapeutics NV | Initiation date: Dec 2023 --> May 2023
    Trial initiation date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • danvatirsen (AZD9150)
    6ms
    PEMDA-HN: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (clinicaltrials.gov)
    P2, N=81, Recruiting, Flamingo Therapeutics NV | Initiation date: Sep 2023 --> Dec 2023
    Trial initiation date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • danvatirsen (AZD9150)
    7ms
    Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase 2 NeoCOAST Platform Trial. (PubMed, Cancer Discov)
    Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). Safety profiles for the combinations were similar to that of durvalumab alone. Multiplatform immune profiling suggested improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune-cell activation.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Immuno-oncology
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3) • KLRC1 (Killer Cell Lectin Like Receptor C1)
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • danvatirsen (AZD9150) • monalizumab (IPH2201)
    8ms
    Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML [(FDA OOPD)] (clinicaltrials.gov)
    P1, N=24, Recruiting, Montefiore Medical Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • danvatirsen (AZD9150)
    9ms
    Phase 1 Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment. (PubMed, Clin Cancer Res)
    Targeting both STAT3 and BTK in combination is safe and tolerable but efficacy is limited in R/R DLBCL. Results support evaluation of circulating tumor DNA as a biomarker for clinical response.
    P1 data • Clinical Trial,Phase I • Journal • IO biomarker • Circulating tumor DNA
    |
    Calquence (acalabrutinib) • danvatirsen (AZD9150)
    9ms
    PEMDA-HN: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (clinicaltrials.gov)
    P2, N=81, Recruiting, Flamingo Therapeutics NV | Initiation date: Jun 2023 --> Sep 2023
    Trial initiation date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • danvatirsen (AZD9150)
    9ms
    Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML [(FDA OOPD)] (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Montefiore Medical Center
    New P1 trial
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • danvatirsen (AZD9150)
    10ms
    PEMDA-HN, an open-label, phase II, randomized controlled study of danvatirsen plus pembrolizumab compared to pembrolizumab alone in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) (ESMO 2023)
    The SCORES Study (ESMO 2018) in RM HNSCC patients naïve to programmed cell death (ligand)1 (PD-(L)1) therapy demonstrated that DAN in combination with the PD-L1 inhibitory antibody durvalumab approximately doubled the objective response rate (ORR) seen with durvalumab alone in previous studies. Exploratory endpoints include but are not limited to target engagement and biomarker evaluation. The study is being conducted at US study centers.
    Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    Keytruda (pembrolizumab) • Imfinzi (durvalumab) • danvatirsen (AZD9150)
    12ms
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=175, Active, not recruiting, AstraZeneca | N=258 --> 175 | Trial completion date: Mar 2026 --> May 2023 | Trial primary completion date: Mar 2026 --> May 2023
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • ALK fusion
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • rilvegostomig (AZD2936) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    12ms
    PEMDA-HN: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (clinicaltrials.gov)
    P2, N=81, Recruiting, Flamingo Therapeutics NV | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • danvatirsen (AZD9150)
    1year
    PEMDA-HN: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (clinicaltrials.gov)
    P2, N=81, Not yet recruiting, Flamingo Therapeutics NV
    New P2 trial • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • danvatirsen (AZD9150)
    1year
    BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P1b, N=156, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2023 --> Sep 2023
    Trial completion date
    |
    HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
    |
    FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)
    1year
    NCI-2018-01296: Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer (clinicaltrials.gov)
    P2, N=53, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2023 --> Apr 2024 | Trial primary completion date: Mar 2023 --> Apr 2024
    Trial completion date • Trial primary completion date • Mismatch repair • IO biomarker • Metastases
    |
    CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    over1year
    AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and in Patients With Non-Small-Cell Lung Cancer (clinicaltrials.gov)
    P1, N=76, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2022 --> Dec 2025
    Trial completion date • Combination therapy • IO biomarker • Metastases
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • danvatirsen (AZD9150)
    over1year
    Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 study. (PubMed, BMJ Open)
    Danvatirsen was well tolerated by Japanese patients with advanced solid tumours as monotherapy and combined with durvalumab. No new safety signals arose.
    P1 data • PK/PD data • Clinical Trial,Phase I • Journal • Combination therapy • PD(L)-1 Biomarker
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STAT3 expression
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    over1year
    BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P1b, N=156, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2022 --> Mar 2023
    Trial completion date
    |
    HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
    |
    FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)
    over1year
    Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck (clinicaltrials.gov)
    P1b/2, N=340, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2022 --> Dec 2023
    Trial completion date • Combination therapy • IO biomarker • Metastases
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab) • AZD5069 • danvatirsen (AZD9150)
    almost2years
    HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed Phase 2 Study in NSCLC Patients Who Progressed on Anti-PD-(L)1 Therapy (IASLC-WCLC 2022)
    P2 | "Here we present mature efficacy and safety results for the initial combinations - durvalumab plus: olaparib (PARP inhibitor; Module 1), danvatirsen (STAT3 inhibitor; Module 2), ceralasertib (ATR inhibitor; Module 3), and oleclumab (anti-CD73 antibody; Module 5). Durvalumab plus ceralasertib demonstrated a promising efficacy signal, with a tolerable safety profile, in patients with advanced/metastatic NSCLC following failure of anti-PD-1/PD-L1-containing immunotherapy and ≥1 platinum-doublet regimen."
    P2 data • Clinical
    |
    PD-L1 IHC 28-8 pharmDx
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • danvatirsen (AZD9150)
    almost2years
    BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P1b, N=156, Active, not recruiting, AstraZeneca | Trial completion date: Feb 2022 --> Sep 2022
    Trial completion date
    |
    HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
    |
    FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)
    2years
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=212, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2024 --> Mar 2026 | Trial primary completion date: Jan 2024 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    2years
    NCI-2018-01296: Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer (clinicaltrials.gov)
    P2, N=53, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2022 --> Mar 2023 | Trial primary completion date: Mar 2022 --> Mar 2023
    Trial completion date • Trial primary completion date • Mismatch repair • IO biomarker
    |
    CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    2years
    C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 7(CXCR7) regulates epithelial-mesenchymal transition process and promotes the metastasis of esophageal cancer by activating signal transducer and activator of transcription 3 (STAT3) pathway. (PubMed, Bioengineered)
    Inhibition of the STAT3 pathway using AZD9150 weakened the accelerated effects of CXCL12/CXCR7 on the growth and metastasis of esophageal cancer in vitro and in vivo. In conclusion, our research revealed that CXCL12/CXCR7 regulates EMT and other malignant processes by activating the STAT3 pathway to accelerate the growth and metastasis of esophageal cancer.
    Journal
    |
    CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • ACKR3 (Atypical Chemokine Receptor 3)
    |
    CXCL12 expression • CXCL12 overexpression
    |
    danvatirsen (AZD9150)
    over2years
    NCI-2018-01296: Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer (clinicaltrials.gov)
    P2, N=53, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Mar 2021 --> Mar 2022
    Clinical • Trial completion date • Trial primary completion date • Mismatch repair • IO biomarker
    |
    CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    over2years
    AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and in Patients With Non-Small-Cell Lung Cancer (clinicaltrials.gov)
    P1, N=76, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2021 --> Dec 2022
    Clinical • Trial completion date • Combination therapy • IO biomarker
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • danvatirsen (AZD9150)
    over2years
    Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck (clinicaltrials.gov)
    P1b/2, N=340, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2021 --> Sep 2022
    Trial completion date • Combination therapy • IO biomarker
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab) • AZD5069 • danvatirsen (AZD9150)
    over2years
    A Transgenic Murine Model Expressing Hyperactive STAT3 Recapitulates the Features of MDS/AML (ASH 2021)
    FDA approved therapies such as the recently approved Bcl-2 inhibitor venetoclax, FLT3 inhibitors, among others, have moved the field forward in newly diagnosed MDS/AML...We have successfully demonstrated that a selective antisense oligonucleotide inhibitor of STAT3, Danvatirsen, is rapidly incorporated into MDS/AML HSPCs and induces selective apoptosis and downregulation of STAT3 in these cells in comparison with healthy control HSPCs...Through the generation of a STAT3C-vavCre mouse model, that recapitulates the features of MDS/AML, we aim to further our understanding of the molecular mechanisms and pathways that play an important role in MDS to AML transformation and will help us identify downstream mediators of this event that can be therapeutically targeted. We would also like to use this murine model as an ideal substrate for preclinical studies of STAT3 targeting therapies in hematologic malignancies such as previously reported antisense inhibitors of STAT3 and STAT3 degraders.
    Preclinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STAT3 expression
    |
    Venclexta (venetoclax) • danvatirsen (AZD9150)
    over2years
    A Phase 1 Study of the Combination of Acalabrutinib and AZD9150 in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (ASH 2021)
    A total of 17 patients were enrolled; median age was 72 (range, 34-88) years and 47% (8/17) of patients were ≥75 years. Median number of prior lines of therapy was 2 (range, 1-6). Overall response rate was 24% with a CR rate of 12%.
    Clinical • P1 data • IO biomarker
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STAT3 expression
    |
    Calquence (acalabrutinib) • CAR T-cell therapy • danvatirsen (AZD9150)
    almost3years
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=212, Active, not recruiting, AstraZeneca | Trial completion date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2023 --> Jan 2024
    Clinical • Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    3years
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=212, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed
    |
    PD-L1 (Programmed death ligand 1)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    3years
    [VIRTUAL] Identification of a novel immunosuppressive myeloid gene expression signature for clinical biomarker development (AACR 2021)
    This led to a 6-gene ‘de novo’ signature (MRC1, APOE, C1QA, C1QB, MMP9, SPP1) associated with IMC function with highly significant concordance (rS = 0.96; p = 1.2e-11) to IMC abundance.Lastly, we showed that in whole blood baseline samples from HNSCC patients (n=53) treated with danvatirsen + durvalumab [NCT02499328], our ‘de novo’ signature was significantly elevated (p=0.033) in patients with progressive disease compared to complete responders. Application to additional studies will be required to more fully determine its clinical utility.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    CD33 (CD33 Molecule) • SPP1 (Secreted Phosphoprotein 1) • ITGAM (Integrin, alpha M) • MMP9 (Matrix metallopeptidase 9) • APOE (Apolipoprotein E) • MRC1 (Mannose Receptor C-Type 1)
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    3years
    A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk)
    The primary endpoint was met, with durvalumab plus tremelimumab/danvatirsen generally well tolerated in patients with relapsed/refractory DLBCL; however, antitumor activity was limited.
    Clinical • P1 data • Journal • Combination therapy
    |
    CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab) • danvatirsen (AZD9150)
    almost4years
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=257, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting
    Clinical • Enrollment open
    |
    PD-L1 (Programmed death ligand 1)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    almost4years
    Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer (clinicaltrials.gov)
    P2, N=53, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed • Mismatch repair • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 expression • STAT3 expression
    |
    Imfinzi (durvalumab) • danvatirsen (AZD9150)
    almost4years
    Differential gene expression analysis of sickle cell anemia in steady and crisis state. (PubMed, Ann Hum Genet)
    For crisis-state patients versus healthy individuals, two networks of regulator effects revealed STAT1, CD40LG, TGM2, IRF7, IRF4, and IRF1 acting as upstream regulators, resulting in disease/function outcomes, including engulfment of cells and aggregation of blood cells and inflammation of joints. Our results indicated genes and pathways that can provide clues on the molecular events involved in the severity of sickle cell disease.
    Journal
    |
    VEGFA (Vascular endothelial growth factor A) • IL6 (Interleukin 6) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • IRF1 (Interferon Regulatory Factor 1) • IRF4 (Interferon regulatory factor 4) • CD40LG (CD40 ligand) • IL1B (Interleukin 1, beta)
    |
    IRF1 expression
    |
    danvatirsen (AZD9150)