ArticleBMJ oncology2024
Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer.
Article in BMJ oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02983578 (Phase II Clinical Trial Evaluating Intravenous AZD9150), which is not on this map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Clinical Trial Evaluating Intravenous AZD9150 (Antisense STAT3) With MEDI4736 (Anti-PD-L1) in Patients With Advanced Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer
Who cites it
12 citing papers in PubMed.
- Review
- An interpretable machine learning model for predicting survival in pancreatic cancer via SHAP: a multicenter study.Journal of gastroenterology · 2026Article
- Advances in antisense oligonucleotide treatment for cancer.Japanese journal of clinical oncology · 2026Review
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Harnessing myeloid cell plasticity for cancer therapy.Nature cancer · 2026Review
- Metachronous primary non-small cell lung cancer and mucinous tubular and spindle cell carcinoma of the left kidney: A case report.Oncology letters · 2026Article
- Review
- STATs Signaling Pathways in Acute Pancreatitis: Mechanisms and Regulation.International journal of medical sciences · 2026Review
- Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- RNA Therapeutics: Delivery Problems and Solutions-A Review.Pharmaceutics · 2025Review
- The multifaceted role of YAP in the tumor microenvironment and its therapeutic implications in cancer.Experimental & molecular medicine · 2025Review
- Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects.Genes · 2025Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Objective: To evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical experiments. Methods and analysis: Orthotopically implanted pancreatic cancer (pancreatic adenocarcinoma (PDAC)) was treated with STAT3 ASO with immune checkpoint inhibition. Tumour infiltrating immune cell populations were characterised via flow cytometry. In vitro experiments evaluated STAT3 inhibition in pancreatic stellate cells (PSCs) and myeloid-derived suppressor cells (MDSCs).A phase II trial employing a Simon II stage design tested the clinical efficacy of danvatirsen and durvalumab in non-small cell lung cancer (NSCLC), PDAC and mismatch repair-deficient colorectal cancer (MRD CRC). The primary objective was 4-month disease control rate (DCR). Results: In vivo studies identified improvement in survival of PDAC implanted mice treated with STAT3 ASO and checkpoint inhibition. Within tumour-infiltrating lymphocytes there was expansion of CD4 and PD-1+ CD8 populations with STAT3 ASO.Thirty-seven patients (29 PDAC, 7 NSCLC and 1 MRD CRC) from a single institution started treatment on trial between April 2017 and March 2020. No objective responses were observed. Four of six (66.7%, 95% CI 22.3% to 95.7%) NSCLC and 4 of 23 (17.4%, 95% CI 5% to 38.8%) PDAC patients exhibited 4-month DCR. Follow-up in vitro studies revealed an anti-inflammatory and pro-tumour effect of STAT3 ASO mediated by PSCs and MDSCs distinct from ablation of STAT3. Conclusion: Although durvalumab and danvatirsen met the primary endpoint, no objective responses were observed. A rationale for the lack of objective responses is danvatirsen-induced myeloid immune suppression. Trial registration number: NCT02983578.
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