Phase 1 pilot study with dose expansion of chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer
| العنوان: | Phase 1 pilot study with dose expansion of chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer |
|---|---|
| المؤلفون: | Sangeetha M. Reddy, Meredith Carter, Isaac Chan, Melanie Hullings, Nisha Unni, Jessica Medina, Shahbano Shakeel, Susan Armstrong, Lakeisha Cade, Farjana J. Fattah, Chul Ahn, Yisheng V. Fang, Nan Chen, Heather L. McArthur, Nicole Sinclair, Michael Jay Yellin, Joyce O'Shaughnessy, Rita Nanda, Suzanne D. Conzen, Carlos L. Arteaga |
| المصدر: | Journal of Clinical Oncology. 40:TPS1126-TPS1126 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | TPS1126 Background: Only a subset of patients with metastatic triple-negative breast cancer demonstrate response to currently approved PD-1 immune checkpoint blockade, and few have durable responses. Antigen presentation defects may be a reason for this low response because deficiency of antigen-presenting DC1 dendritic cells is associated with poor anti-tumor immunity. CD40 agonists are a class of agents that activate antigen presenting cells including dendritic cells and B cells and also repolarize macrophages. Flt3 ligand is a growth factor that increases dendritic cells. In line with this, we recently demonstrated in pre-clinical models that the combination of liposomal-doxorubicin chemotherapy, a CD40 agonist, and a Flt3 ligand improves outcomes of breast cancer compared to alternate combinations. Methods: This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic triple-negative breast cancer. Patients will be randomized to 3 lead-in arms (triplet therapy, doublet immunotherapy only, liposomal-doxorubicin only) prior to receiving full triplet therapy with fresh tissue biopsies before and after the lead-in treatment. CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Primary endpoint is determination of a recommended phase 2 dose based on treatment-related adverse events including dose-limiting toxicities. Secondary endpoints include anti-tumor immune response after triplet therapy, after immunotherapy alone, and after liposomal-doxorubicin alone; median progression-free survival, overall response rate, duration of response, and clinical benefit rate. Key eligibility criteria are unresectable stage III or stage IV triple-negative breast cancer (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites. Clinical trial information: NCT05029999. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::7bf8e9ffec885106c1d93420bdb3655eTest https://doi.org/10.1200/jco.2022.40.16_suppl.tps1126Test |
| رقم الانضمام: | edsair.doi...........7bf8e9ffec885106c1d93420bdb3655e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
|---|