دورية أكاديمية
STARLITE 1: Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naïve patients with advanced clear cell RCC
| العنوان: | STARLITE 1: Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naïve patients with advanced clear cell RCC |
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| المؤلفون: | Hasanov, Elshad, Flynt, Lesley, Slack Tidwell, Rebecca, Hwang, Hyunsoo, Brooks, Roserika, King, Lauren, Solley, Travis, Syed, Mashaal, Yamamura, Yuko, Hayward, Colin, Venkatesan, Aradhana M, Jonasch, Eric |
| المصدر: | The Oncologist ; volume 28, issue Supplement_1, page S13-S13 ; ISSN 1083-7159 1549-490X |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | Background Complete response (CR) is still a rare event in patients with advanced clear cell renal cell carcinoma (ccRCC). The combination of nivolumab plus cabozantinib was recently approved for the first-line treatment of ccRCC based on the CheckMate 9ER phase 3 study demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib. However, the CR rate was only 9%. Since the anti-tumor effects of immune checkpoint inhibitors are dependent on the presence of activated tumor-infiltrating T cells, drugs that could synergize with T cells’ anti-tumor activity can allow us to improve CR rates. Activation of the cGAS-STING pathway, the master regulator of anti-tumor immunity which is induced by radiation-induced DNA damage, is one promising mechanism that has been investigated. Many studies have shown that radiation treatment augments immune checkpoint inhibition. However, it is not always possible to radiate all metastatic lesions. Therefore, targeted peptide receptor radionuclide therapies (PRRT), have been developed by conjugating radioisotopes to receptor binding analogs targeting specific cancer cell surface proteins, thereby delivering targeted radiation to cancer cells in the body with minimal damage to surrounding healthy cells. 177Lu girentuximab is the first antibody-radioisotope designed for ccRCC, targeting carbonic anhydrase IX-expressing cells, which includes >90% of ccRCC. It has been tested in metastatic ccRCC as a single agent and shown to be safe and effective in stabilizing disease in 57% of pts. In this study, we hypothesize that 177Lu girentuximab-induced DNA damage will potentiate the STING pathway, and this activation will synergize with nivolumab and cabozantinib to promote trafficking and infiltration of activated T cells to tumors and achieve higher CR rates. Methods Up to 100 patients with treatment naïve, biopsy-proven ccRCC with adequate organ/marrow function with ≥1 evaluable lesion by RECIST 1.1 will be enrolled. A ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/oncolo/oyad216.021 |
| الإتاحة: | https://doi.org/10.1093/oncolo/oyad216.021Test https://academic.oup.com/oncolo/article-pdf/28/Supplement_1/S13/51234186/oyad216.021.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.F7B44CEB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/oncolo/oyad216.021 |
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