Publications by authors named "D W Rasco"
Purpose: In this phase 1 portion of a first-in-human phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.
Patients And Methods: Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks (Q3W) using an accelerated titration design followed by a traditional 3 + 3 design, with an initial dose level of 2 mg.
Article Synopsis
- BMS-986365 is a novel oral treatment for metastatic castration-resistant prostate cancer (mCRPC), targeting the androgen receptor (AR) through a unique dual mechanism that both degrades and antagonizes it.
- In a Phase 1 clinical trial involving 95 patients, the drug was found to be well tolerated, with common but manageable side effects, and showed signs of effectiveness, particularly in patients who had not previously undergone chemotherapy.
- The primary goals of the study included assessing safety and determining the highest dose that could be tolerated, while key outcomes such as a significant drop in prostate-specific antigen levels and improved progression-free survival were also evaluated.
Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently in advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative chromatin state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability in the context of ARID1A mutations. In this study, we describe the discovery of tulmimetostat, an orally available, clinical stage EZH2 inhibitor, and it elucidates the aspects of its application potential in ARID1A mutant tumors.
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- MEK inhibitors show potential for immune modulation and may work well with PD-1 inhibitors, leading to a study of selumetinib (a MEK inhibitor) combined with pembrolizumab (an anti-PD-1 antibody) in patients with advanced solid tumors.
- In this phase 1b trial, 32 patients received a specific schedule of pembrolizumab and selumetinib, with toxicity and safety being primary concerns; dose adjustments were made based on the side effects experienced.
- While the study did not reach its target for dose-limiting toxicities and found no new safety concerns, the combination treatment resulted in limited tumor response, leading to the decision to stop the trial early due to insufficient efficacy
Article Synopsis
- Retifanlimab is a monoclonal antibody targeting PD-1, undergoing a phase I study to assess its safety and optimal dosing for patients with advanced solid tumors.
- The study had two parts: dose escalation with varying doses of retifanlimab and a cohort expansion for specific tumor types like endometrial and non-small-cell lung cancer (NSCLC), focusing on safety and efficacy.
- Results showed no dose-limiting toxicities, with a selected expansion dose of 3 mg/kg every 2 weeks, but only a modest objective response rate (up to 20%) in tumor-specific cohorts, alongside significant immune-related adverse events in some patients.