Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T
| Autor: | Tanya B. Dorff, Jared David Acoba, Yosuke Hirasawa, Hideki Furuya, Mark Scholz, Minlu Zhang, Charles J. Rosser, John Shon, Jeffrey Huang, Winston A. Haynes, David Jon Tamura, Sumanta K. Pal, Abhilash Dhal, Rebecca Waitz, Owen T. M. Chan, Ian Pagano |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Immunology Antibodies Monoclonal Humanized prostatic neoplasms Drug Administration Schedule Prostate cancer Antigen Atezolizumab Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Immunology and Allergy Humans Neoplasm Metastasis Adverse effect RC254-282 Aged Pharmacology Clinical/Translational Cancer Immunotherapy Aged 80 and over business.industry Tissue Extracts Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged medicine.disease Prostate-specific antigen Sipuleucel-T Prostatic Neoplasms Castration-Resistant Response Evaluation Criteria in Solid Tumors translational medical research Molecular Medicine business medicine.drug |
| Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 9, Iss 8 (2021) |
| ISSN: | 2051-1426 |
| Popis: | BackgroundCombining an immune checkpoint inhibitor with a tumor vaccine may modulate the immune system to leverage complementary mechanisms of action that lead to sustained T-cell activation and a potent prolonged immunotherapeutic response in metastatic castration resistant prostate cancer (mCRPC).MethodsSubjects with asymptomatic or minimally symptomatic mCRPC were randomly assigned in a 1:1 ratio to receive either atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2). The primary endpoint was safety, while secondary endpoints included preliminary clinical activity such as objective tumor response and systemic immune responses that could identify key molecular and immunological changes associated with sequential administration of atezolizumab and sipuleucel-T.ResultsA total of 37 subjects were enrolled. The median age was 75.0 years, median prostate specific antigen (PSA) was 21.9 ng/mL, and subjects had a median number of three prior treatments. Most subjects (83.8%) had at least one treatment-related adverse event. There were no grade 4 or 5 toxicities attributed to either study drug. Immune-related adverse events and infusion reactions occurred in 13.5% of subjects, and all of which were grade 1 or 2. Of 23 subjects with Response Evaluation Criteria in Solid Tumors measurable disease, only one subject in Arm 2 had a partial response (PR) and four subjects overall had stable disease (SD) at 6 months reflecting an objective response rate of 4.3% and a disease control rate of 21.7%. T-cell receptor diversity was higher in subjects with a response, including SD. Immune response to three novel putative antigens (SIK3, KDM1A/LSD1, and PIK3R6) appeared to increase with treatment.ConclusionsOverall, regardless of the order in which they were administered, the combination of atezolizumab with sipuleucel-T appears to be safe and well tolerated with a comparable safety profile to each agent administered as monotherapy. Correlative immune studies may suggest the combination to be beneficial; however, further studies are needed.Trial registration numberNCT03024216. |
| Databáze: | OpenAIRE |
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