Publications by authors named "Cyrus Sayehli"
Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.
View Article and Find Full Text PDFWe report results of a first-in-human study of pasotuxizumab, a PSMA bispecific T-cell engager (BiTE) immune therapy mediating T-cell killing of tumor cells in patients with advanced castration-resistant prostate cancer. We assessed once-daily subcutaneous (SC) pasotuxizumab. All SC patients developed antidrug antibodies; therefore, continuous intravenous (cIV) infusion was assessed.
View Article and Find Full Text PDFBackground: To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M SGC.
Methods: The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019.
Article Synopsis
- * A long-term follow-up study of 38 patients indicated no significant long-term toxicities, particularly neurocognitive impairments, after blinatumomab treatment.
- * The median overall survival for all patients was 4.6 years, with those receiving the maximum tolerated dose of 60 µg/m per day achieving a median survival of 7.7 years, suggesting this dose is key for long-lasting remission in B-NHL cases.
Background: The clinical activity of fibroblast growth factor receptor (FGFR) inhibitors seems restricted to cancers harbouring rare FGFR genetic aberrations. In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor. We aimed to assess the safety, maximum tolerated dose, recommended phase 2 dose, pharmacokinetics, and preliminary clinical activity of rogaratinib.
View Article and Find Full Text PDFObjectives: Domatinostat (4SC-202) is a selective class I histone deacetylase inhibitor (HDACi). This phase I study investigated safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity in patients with advanced hematological malignancies.
Methods: Domatinostat was administered orally once (QD) or twice daily (BID) on days 1-14 with 7 days off or continuously days 1-21 in a 3 + 3 design at 7 dose levels from 25 to 400 mg total daily dose (TDD).
Article Synopsis
- A phase 2 study evaluated the effectiveness of blinatumomab, a bispecific T-cell engaging antibody, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), showing a 43% overall response rate and 19% complete responses after one treatment cycle.
- Participants had a median of 3 previous therapies, with a range of dosing strategies used; however, many experienced adverse events, particularly neurologic issues, with some requiring treatment discontinuation.
- The flat-dose approach was halted due to severe neurologic side effects, indicating the need for further research to optimize dosing while minimizing adverse effects in this high-need patient population.
So-called RAS-dependent pathways, such as those signalling via mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3K)/Akt, are implicated in proliferation and survival of multiple myeloma (MM) cells. However, the effects of their combined blockade and its potential therapeutic utility for the treatment of RAS-mutated MM have not systematically been analysed. Here, we tested the functional consequences of single versus combined inhibition of the MEK/MAPK and PI3K/Akt pathways in a large series of primary MM samples (n = 55) and MM cell lines (n = 11).
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