B7-H3 Antibody-Drug Conjugate Dosing Regimens with PD-1 CTLA-4 Bispecifics
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Solution Overview
Problem
Current treatments for cancer associated with B7-H3 expression are limited in efficacy, and there is a need for novel dosing regimens that combine B7-H3 antibody-drug conjugates (ADCs) with other immunotherapeutic agents to enhance cancer treatment outcomes.
Innovation Solution
The use of B7-H3-ADCs in combination with a PD-1×CTLA-4 bispecific molecule, such as lorigerlimab, for the treatment of cancer, employing dosing regimens that include single or fractionated doses administered at regular or intermittent intervals, either simultaneously or sequentially.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for B7-H3 expressing cancers are used, then treatment simplicity is maintained, but treatment efficacy is limited
Solution Approach 1:
The patent combines B7-H3-ADC therapy with PD-1×CTLA-4 bispecific molecule therapy into a single treatment regimen. This merging of two therapeutic approaches (targeted cytotoxic delivery and immune checkpoint inhibition) into a coordinated treatment protocol resolves the contradiction by achieving enhanced efficacy through combination therapy while providing a unified administration strategy that manages the complexity of treating B7-H3 expressing cancers
2Reliability
If B7-H3-ADC is administered as a single dose, then treatment simplicity is improved, but treatment efficacy may be insufficient
Solution Approach 1:
The patent employs periodic administration of B7-H3-ADC at defined intervals (e.g., every 2-4 weeks) rather than continuous or single-dose regimens. This periodic action allows the cytotoxic payload to be delivered in controlled cycles that maintain therapeutic efficacy while managing toxicity, resolving the contradiction between achieving sufficient treatment effect and maintaining dosing simplicity through standardized periodic protocols
3Reliability
If B7-H3-ADC is administered in combination with PD-1×CTLA-4 bispecific molecule, then treatment efficacy is enhanced, but treatment complexity increases
Solution Approach 1:
The patent uses the B7-H3-ADC as an intermediary that delivers cytotoxic payload specifically to B7-H3 expressing tumor cells, while the PD-1×CTLA-4 bisspecific molecule acts as a mediator that enhances immune response. The coordinated action of these two therapeutic agents, each targeting different mechanisms (direct cytotoxicity and immune modulation), resolves the contradiction by achieving synergistic efficacy while maintaining distinct but complementary roles that manage combination therapy complexity
Data Source
AI summary
The present disclosure is directed in part to dosing regimens for administering a humanized anti-B7-H3 antibody conjugated to a duocarmycin moiety (a “B7-H3-ADC”) for the treatment of cancer, particularly a cancer associated with expression of B17-H3. The disclosure in part concerns the use of such B7-H3-ADC in combination with a bispecific molecule capable of binding to PD-1 and CTLA-4 (“PD-1×CTLA-4 bispecific molecule”). The disclosure in pant concerns the use of such B7-H3-ADC in combination with lorigerlimab for the treatment of cancer. The disclosure in part concerns the use of MGC018 in combination with lorigerlimab for the treatment of cancer. The disclosure is directed in part to the use of such molecules, and to the use of pharmaceutical compositions and pharmaceutical kits that contain such molecules and that facilitate the use of such dosing regimens in the treatment of cancer.