Bispecific T-cell Engaging Molecule Priming Dose Administration
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Solution Overview
Problem
Current bispecific T-cell engaging molecules for cancer treatment often result in cytokine release syndrome (CRS) due to rapid peak serum concentrations, leading to adverse events, and existing strategies to mitigate these effects can impact therapeutic efficacy.
Innovation Solution
Administering a priming dose of bispecific T-cell engaging molecules via continuous intravenous infusion over an extended period, followed by a therapeutic dose via bolus intravenous infusion or subcutaneous injection, to reduce peak serum concentrations and minimize adverse events while maintaining effective drug exposure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If bispecific T-cell engaging molecules are administered by short-term intravenous infusion at treatment initiation, then rapid therapeutic effect is achieved, but peak serum concentrations increase leading to cytokine release syndrome and adverse events
Solution Approach 1:
The patent applies preliminary action by administering a priming dose via continuous intravenous infusion over an extended period (e.g., 24-72 hours) before administering the full therapeutic dose. This preliminary continuous infusion primes the patient's system gradually, reducing the risk of cytokine release syndrome when the full therapeutic dose is subsequently administered by bolus injection or short-term infusion, thereby enabling rapid therapeutic effect while mitigating adverse events
Solution Approach 2:
The patent segments the therapeutic dosing into two distinct phases: (1) a priming dose administered by continuous intravenous infusion over an extended period to gradually expose the patient to the bispecific T-cell engaging molecule, and (2) a subsequent therapeutic dose administered by bolus injection or short-term infusion to achieve rapid therapeutic effect. This segmentation allows the total therapeutic dose to be delivered while avoiding peak concentration-related adverse events
2Object-affected harmful factors
If bisspecific T-cell engaging molecules are administered by continuous intravenous infusion over extended period, then peak serum concentrations are reduced minimizing adverse events, but time to achieve therapeutic dose is prolonged
Solution Approach 1:
The continuous intravenous infusion over an extended period serves as a preliminary action that prepares the patient's system for subsequent therapeutic dosing. By administering a priming dose continuously over 24-72 hours, the patent minimizes peak serum concentrations and adverse events during this initial phase, while the subsequent bolus injection or short-term infusion rapidly achieves the full therapeutic dose, thereby limiting the overall time loss
Solution Approach 2:
The patent employs periodic action by using a continuous infusion protocol for a defined period (e.g., 24-72 hours) followed by intermittent bolus injections or short-term infusions at scheduled intervals. This periodic approach allows the patient to tolerate the initial continuous exposure while maintaining therapeutic drug levels through subsequent periodic dosing, balancing adverse event reduction with timely achievement of therapeutic effect
Data Source
AI summary
The present invention relates to methods for administering therapeutic doses of bispecific T-cell engaging molecules for the treatment of cancer in a patient. The administration methods reduce the incidence and/or severity of adverse events, such as cytokine release syndrome, and entail administering to a patient a priming dose of the bispecific T-cell engaging molecule by continuous intravenous infusion over a period of days followed by administration of a therapeutic dose of the bispecific T-cell engaging molecule by a bolus intravenous infusion at dosing intervals of at least a week.