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    DRUG:

    AZD0171

    i
    Other names: AZD0171, MSC-1, MSC 1, MSC1, AZD-0171, AZD 0171
    Associations

    News

    Trials
    Company:
    AstraZeneca, Boehringer Ingelheim
    Drug class:
    LIF inhibitor
    Related drugs:
    Associations

    News

    Trials
    2ms
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=490, Recruiting, AstraZeneca | Trial completion date: Dec 2029 --> May 2030 | Trial primary completion date: Dec 2029 --> May 2030
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    3ms
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=490, Recruiting, AstraZeneca | Trial completion date: Dec 2028 --> Dec 2029 | Trial primary completion date: Dec 2028 --> Dec 2029
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    4ms
    A mechanistic PK/PD model of AZD0171 (anti-LIF) to support Phase II dose selection. (PubMed, CPT Pharmacometrics Syst Pharmacol)
    The aim of this work was to develop a mechanistic PK/PD model to investigate the effect of AZD0171 on tumor LIF levels, predict the level of downstream signaling complex (LIF:LIFR:gp130) inhibition, and examine the dose-response relationship to support dose selection for a Phase II clinical study. Modeling results show that tumor LIF is inhibited in a dose-dependent manner with >90% inhibition for 95% of patients at the Phase II clinical dose of 1500 mg Q2W.
    P2 data • PK/PD data • Journal
    |
    IL6 (Interleukin 6) • STAT3 (Signal Transducer And Activator Of Transcription 3) • LIFR (LIF Receptor Subunit Alpha) • LIF (LIF Interleukin 6 Family Cytokine)
    |
    AZD0171
    9ms
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=490, Recruiting, AstraZeneca | N=350 --> 490
    Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    1year
    Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours (clinicaltrials.gov)
    P2, N=126, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    CD8 (cluster of differentiation 8) • CA 19-9 (Cancer antigen 19-9)
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • AZD0171
    1year
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=350, Recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Dec 2028 | Trial primary completion date: Mar 2026 --> Dec 2028
    Trial completion date • Trial primary completion date • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    over1year
    Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours (clinicaltrials.gov)
    P2, N=115, Recruiting, AstraZeneca | Trial completion date: Oct 2023 --> Nov 2024 | Trial primary completion date: Oct 2023 --> Nov 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD8 (cluster of differentiation 8) • CA 19-9 (Cancer antigen 19-9)
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • AZD0171
    over1year
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=350, Recruiting, AstraZeneca | N=210 --> 350
    Enrollment change • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    almost2years
    Therapeutic targeting of LIF overcomes macrophage mediated immunosuppression of the local tumor microenvironment. (PubMed, Clin Cancer Res)
    Overall, our findings highlight LIF as a therapeutic target for cancer immunotherapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    LIFR (LIF Receptor Subunit Alpha)
    |
    AZD0171
    2years
    Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours (clinicaltrials.gov)
    P2, N=115, Recruiting, AstraZeneca | Trial completion date: Mar 2024 --> Oct 2023 | Trial primary completion date: Mar 2024 --> Oct 2023
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD8 (cluster of differentiation 8) • CA 19-9 (Cancer antigen 19-9)
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • AZD0171
    2years
    Phase I, first-in-human study of MSC-1 (AZD0171), a humanized anti-leukemia inhibitory factor monoclonal antibody, for advanced solid tumors. (PubMed, ESMO Open)
    MSC-1 was very well tolerated across doses, with prolonged PFS in some patients. Biomarker and preclinical data suggest potential synergy with checkpoint inhibitors.
    P1 data • Journal
    |
    CD8 (cluster of differentiation 8)
    |
    AZD0171
    over2years
    AZD0171 (anti-LIF) combines productively with chemotherapy and anti-PD-L1 in mouse models of cancer (AACR 2022)
    In a non-small cell lung carcinoma patient derived xenograft model, AZD0171 improved the tumor growth inhibitory effect of Carboplatin + Paclitaxel...mAZD0171 addition to oxaliplatin (OHP) or Docetaxel (DTX) chemotherapy plus anti-PD-L1 significantly elevated CD8 abundance and granzyme B expression in MC38 colon tumors...Together these data support the hypothesis that AZD0171 has the potential to sensitize solid tumors to chemotherapy/IO combinations. The safety and activity of AZD0171 is currently being assessed in a Ph2 clinical trial in combination with durvalumab (anti-PD-L1) and chemotherapy in metastatic pancreatic cancer (NCT04999969).
    Preclinical • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • CD44 (CD44 Molecule) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • GZMB (Granzyme B) • LIFR (LIF Receptor Subunit Alpha) • MRC1 (Mannose Receptor C-Type 1)
    |
    carboplatin • Imfinzi (durvalumab) • paclitaxel • docetaxel • oxaliplatin • AZD0171
    almost3years
    Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours (clinicaltrials.gov)
    P2, N=115, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    CD8 (cluster of differentiation 8) • CA 19-9 (Cancer antigen 19-9)
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • AZD0171
    over3years
    Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours (clinicaltrials.gov)
    P2, N=115, Not yet recruiting, AstraZeneca
    Clinical • New P2 trial • Combination therapy
    |
    CD8 (cluster of differentiation 8) • CA 19-9 (Cancer antigen 19-9)
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • AZD0171
    over4years
    [VIRTUAL] Phase 1 dose escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients with advanced solid tumors (AACR-I 2020)
    The most common considered drug-related AEs were fatigue (N=8, 20%) and gastrointestinal disorder (N=8, 20%), and there was 1 considered drug-related SAE (Gr 2 osteonecrosis of jaw in a head and neck cancer patient who previously received radiation to the area and denosumab). Analysis of paired biopsies collected from matched metastatic lesions supported MSC-1 mediated STAT3 signaling inhibition, stimulatory (M1) to suppressive (M2) macrophage skewing in the majority of paired biopsies evaluated and increased CD8 T-cell infiltration in a subset of samples.Single agent MSC-1 was well tolerated in doses ranged from 75 mg to 1500 mg IV OD in patients with advanced solid tumors, showed promising activity as an anti-cancer therapy, and is Phase 1b/2 ready for combination with other agents. The updated final safety, efficacy, PK, LIF stabilization analyses, and tumor biopsy data will be presented.
    Clinical • P1 data
    |
    CD8 (cluster of differentiation 8)
    |
    Prolia (denosumab) • AZD0171