ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
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- Targeting lncRNA MALAT1 attenuates lenalidomide resistance via CD38 epigenetic modulation, oxidative stress-mediated cell death, and remodeling of the pro-tumor microenvironment in multiple myeloma.Journal of translational medicine · 2025Article
- Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy.Cytokine & growth factor reviews · 2025Review
- STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASCancer science · 2025Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- BP1003 Decreases STAT3 Expression and Its Pro-Tumorigenic Functions in Solid Tumors and the Tumor Microenvironment.Biomedicines · 2024Article
- Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review).International journal of oncology · 2024Review
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
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Authors and funding
20 authors at 11 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNovel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL. PATIENTS AND
methodsFinal results of the phase I study of acalabrutinib plus STAT3 inhibitor (danvatirsen; AZD9150) in patients with R/R DLBCL are reported. Danvatirsen 200 mg intravenous infusion [Days 1, 3, 5 (Cycle 1); weekly infusions starting Day 8, Cycle 1] was administered in combination with oral acalabrutinib 100 mg twice daily until progressive disease (PD) or unacceptable toxicity. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.
resultsSeventeen patients received combination treatment. One dose-limiting toxicity (Grade 3 liver transaminase) occurred in 1 patient. The most common reason for treatment discontinuation was PD (65%). In evaluable patients (n = 17), objective response rate was 24%; median duration of response was 1.9 months. All responders with available DLBCL cell-of-origin data were either activated B-cell or nongerminal center B-cell like subtype. Genetic subtype did not correlate with response. Baseline and longitudinal plasma cell-free DNA (cfDNA) concentrations were mostly higher in nonresponding patients. cfDNA changes were generally concordant with imaging. Pretreatment circulating B-cell levels were higher in responders versus nonresponders.
conclusionsTargeting 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.
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Registered trials
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