Publications by authors named "V Upreti"
The Project Optimus initiative from the FDA introduced a new dose optimization and selection paradigm in oncology drug development. The FDA has outlined approaches to dose optimization for single agents, but multiple oncology drugs are being developed for use in combination with other therapies. Dose optimization in the context of combination drug development is complex and requires a case-by-case approach.
View Article and Find Full Text PDFT-cell-engaging bispecific antibodies (TCEs) that target tumor antigens and T cells have shown great promise in treating cancer, particularly in hematological indications. The clinical development of TCEs often involves a lengthy first-in-human (FIH) trial with many dose-escalation cohorts leading up to an early proof of concept (POC), enabling either a no-go decision or dose selection for further clinical development. Multiple factors related to the target, product, disease, and patient population influence the efficacy and safety of TCEs.
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- Bispecific T-cell engagers (Bi-TCEs) are innovative cancer treatments that have shown promise for both blood cancers and solid tumors, but starting dose selection for early human trials is complex due to risks of toxicity and ineffectiveness.
- The traditional method for determining doses often leads to long escalation periods, while a new modified approach uses better-targeted biological data and dosages that match the tumor environment, minimizing risks.
- This new method was successfully applied in a trial for a Bi-TCE targeting gastric cancer, allowing for a much higher initial dose that was safe and well-tolerated, which could expedite future clinical developments for Bi-TCEs in various cancer types.
A novel Bayesian generative approach for estimating tumor dynamics from published studies.
CPT Pharmacometrics Syst Pharmacol
August 2024
Tumor growth inhibition (TGI) modeling attempts to describe the time course changes in tumor size for patients undergoing cancer therapy. TGI models present several advantages over traditional exposure-response models that are based explicitly on clinical end points and have become a popular tool in the pharmacometrics community. Unfortunately, the data required to fit TGI models, namely longitudinal tumor measurements, are sparse or often not available in literature or publicly accessible databases.
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- The landscape of oncology drug development has improved significantly, leading to better patient outcomes and quality of life, particularly through initiatives like Project Optimus by the FDA.
- Project Optimus aims to reform how drug doses are selected in oncology, shifting the focus from maximum tolerated doses to more personalized strategies that consider disease and patient specifics.
- The Oncology Dose Optimization IQ Working Group emphasizes the need for a tailored, evidence-based approach to dose optimization, acknowledging industry's challenges and advocating for strategies that adapt to various factors in cancer treatment.