VEGF and its high affinity receptor VEGFR-2 are crucial for the formation of new tumour vessels. Tumours induce blood vessel growth (angiogenesis) by secreting growth factors such as the Vascular Endothelial Growth Factor (VEGF), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF). Registered AugProspectively registered.Īngiogenesis is a key mechanism in tumour growth and development of metastases. Early tumoral and circulating immune factors were associated with cancer outcome under nintedanib & pembrolizumab therapy. Nintedanib 150 mg bid is the recommended dose for combination with pembrolizumab and is currently investigated in multiple expansion cohorts. After the first pembrolizumab infusion, patients with DCB showed lower IL-6, IL-8, IL-27 plasma levels. For DCB patients, the nintedanib lead-in monotherapy resulted in higher blood CC元, Tregs and CCR4 + CXCR3 + CXCR5 − memory CD4 T cells. Patients with DCB presented also with more DC-LAMP + dendritic cells, CD3 + T cells and FOXP3 + Tregs in baseline tumor biopsies. At baseline, patients with DCB had higher plasma levels of Tie2, CXCL10, CCL22 and circulating CD4 + PD1 + OX40 + T cells than patients without DCB. Three patients developed a partial response (PR) (ORR = 25%) and five patients (42%) had durable clinical benefit (DCB), defined as PR or stable disease (SD) ≥ 6 months.
Eight patients died because of cancer progression. Four patients developed grade 1–2 immune related adverse events (irAE). Three patients at 200 mg bid experienced a DLT (grade 3 liver enzymes increase). ResultsĪ total of 12/13 patients enrolled were evaluable for DLT (1 patient withdrew consent prior receiving pembrolizumab). Flow cytometry (FC), Immuno-Histo-Chemistry (IHC) and electrochemiluminescence multi-arrays were prospectively performed on baseline & on-treatment tumor and blood samples to identify immune correlates of efficacy. Secondary objectives were to assess the anti-tumor efficacy and to identify the associated immune and angiogenic parameters in order to establish the recommended nintedanib dose for expansion cohorts. The primary objective was to establish the maximum tolerated dose (MTD) of the combination based on dose limiting toxicity (DLT) occurrence during the first 4 weeks. Patients received a 1-week lead-in dose of nintedanib monotherapy prior starting pembrolizumab. In this monocentric phase Ib dose escalation cohort, we evaluated escalating doses of nintedanib (Dose level 1 (DL1) = 150 mg bid DL2 = 200 mg bid, oral delivery) in combination with pembrolizumab (200 mg Q3W, IV).
#LISA ARGEN BIO TRIAL#
We aimed to determine the safety and efficacy of nintedanib, an oral anti-angiogenic tyrosine kinase inhibitor, in combination with pembrolizumab, an anti-PD1 immunotherapy, in patients with advanced solid tumors (PEMBIB trial NCT02856425). Journal of Experimental & Clinical Cancer Research volume 41, Article number: 217 ( 2022) He has worked at television station stops in Nebraska, Louisiana, Arkansas, North Carolina, and Minnesota.Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers
Mike graduated from the University of Kansas, with a degree in Atmospheric Science and an AMS Television Seal of Approval.
They are a very active family always making the most of all the Bay Area has to offer. Mike and his wife enjoy volunteering as much as they can at their son’s schools. You are more likely to find them at the pool or beach, jumping on the trampoline, or riding bikes. Mike and the other seven members of his family wife Barbara, two sons, two cats, one fish, and one frog are enjoying their life in the Bay Area. His age is unknown but will be updated as soon as possible. He has never revealed his year month and date of birth in public. Mike Nicco is an American meteorologist for the weekday ABC7 Morning News. Information You May Need To Know About Mike Photo
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