2021
DOI: 10.1016/j.jtocrr.2021.100206
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Phase 1b Open-Label Trial of Afatinib Plus Xentuzumab (BI 836845) in Patients With EGFR Mutation-Positive NSCLC After Progression on EGFR Tyrosine Kinase Inhibitors

Abstract: having research grants from AstraZeneca and Merck Sharp & Dohme; and serving as data monitoring committee member for Incyte and BeiGene. Dr. Tan reports having advisory role/serving as consultant/having research grants from Novartis, Bayer, and AstraZeneca; having advisory role/honoraria from Boehringer Ingelheim and Pfizer; having advisory role/serving as consultant from Celgene, Eli Lilly, Loxo Oncology, Takeda Pharmaceutical, and Merrimack; having honoraria from Merck and Roche; and having research grants f… Show more

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Cited by 4 publications
(4 citation statements)
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“…The therapeutic use of anti-IGF-2 neutralizing antibodies may offer better tolerability by avoiding hyperglycemia, a common side effect of small molecule IGF1R inhibitors, due to cross-reaction with the Insulin Receptor. Indeed, a clinical trial using an anti-IGF1/2 antibody has shown excellent tolerability [ 31 ]. However, in our model, small molecule tyrosine kinase inhibitors showed much stronger efficacy, resulting in a complete loss of viability of meningioma cells, while neutralizing antibodies had only a modest effect on the metabolic rate.…”
Section: Discussionmentioning
confidence: 99%
“…The therapeutic use of anti-IGF-2 neutralizing antibodies may offer better tolerability by avoiding hyperglycemia, a common side effect of small molecule IGF1R inhibitors, due to cross-reaction with the Insulin Receptor. Indeed, a clinical trial using an anti-IGF1/2 antibody has shown excellent tolerability [ 31 ]. However, in our model, small molecule tyrosine kinase inhibitors showed much stronger efficacy, resulting in a complete loss of viability of meningioma cells, while neutralizing antibodies had only a modest effect on the metabolic rate.…”
Section: Discussionmentioning
confidence: 99%
“…A body of literature has reported evidence of resistance to anti-IGF-1R therapies. Non-competitive overactivation of IGF-1R signaling (through mutations) support NSCLC resistance to xentuzumab (BI 836845), a monoclonal antibody targeting both IGF-1 and IGF-2 ( 72 ). In addition, drug resistance is also conferred by Src and AXL membrane tyrosine kinases ( 73 ).…”
Section: Challenges For Clinical Use Of Igf-1r-silencing Agentsmentioning
confidence: 99%
“…Xentuzumab has also been assessed in combination with afatinib in patients with advanced epidermal growth factor receptor mutation‐positive non–small‐cell lung cancer (NSCLC). Although treatment was well tolerated, the combination did not show significant clinical activity 8 . The combination of xentuzumab and enzalutamide vs enzalutamide alone was also evaluated in a phase 2 trial in patients with metastatic castration‐resistant prostate cancer that had progressed after docetaxel and abiraterone.…”
Section: Introductionmentioning
confidence: 99%
“…Although treatment was well tolerated, the combination did not show significant clinical activity. 8 The combination of xentuzumab and enzalutamide vs enzalutamide alone was also evaluated in a phase 2 trial in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel and abiraterone. Although the safety profile was generally similar between treatment arms, addition of xentuzumab to enzalutamide did not prolong progression-free survival vs enzalutamide alone.…”
mentioning
confidence: 99%