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Clinical development of 2NME-based oncology treatment regimens
C L Jones1, G Lieberman, L Kaiser
1Genentech, Inc. 1 DNA Way, South San Francisco, CA 94080, USA. jones.cheryl@gene.com
Abstract:
Over the past decade many signaling pathways have been identified and implicated in cancer development. This has lead to rational drug development of many new molecules that target specific nodes on one or more signaling pathways. It is now believed that targeting key parallel or compensatory pathways may require combining two or more new molecular entities (2NMEs). This approach to drug development differs from the classic case where a single component of a new combination regimen has yet to receive FDA approval. The approach presents numerous challenges to both regulatory authorities and industry sponsors. Of course, the key challenge is the usual demonstration of both safety and efficacy of the proposed combination. In addition, however, superiority of the 2NME-based regimen over both of the individual NME-based regimens and the standard of care (SOC) must be demonstrated. If the individual NME-based regimens are not very effective, then it is desirable to demonstrate the superiority of the 2NME-based regimen as early as possible in the clinical development program so that the number of patients exposed to an ineffective regimen is minimized. In this manuscript we present several strategies for clinical development programs for a 2NME-based oncology regimen. We make recommendations regarding settings where the proposed development strategies are most well suited.
Insights
Developing new cancer drugs often involves combining two new molecular entities (2NMEs). This strategy requires demonstrating the safety and superiority of the 2NME combination over individual treatments and standard care.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trial Design
Background:
- Cancer development is linked to numerous signaling pathways.
- Targeted therapies using new molecular entities (NMEs) are a focus of drug development.
- Combining NMEs may be necessary to target parallel or compensatory pathways.
Purpose of the Study:
- To present strategies for clinical development of two new molecular entities (2NME) oncology regimens.
- To address challenges in regulatory approval and clinical trial design for 2NME combinations.
- To recommend optimal settings for proposed development strategies.
Main Methods:
- Review of current drug development paradigms for combination therapies.
- Analysis of regulatory and industry challenges for 2NME regimens.
- Proposal of clinical development strategies tailored for 2NME oncology combinations.
Main Results:
- The development of 2NME regimens presents unique regulatory and clinical challenges.
- Demonstrating safety, efficacy, and superiority over individual NMEs and standard of care is crucial.
- Early demonstration of superiority is desirable to minimize patient exposure to ineffective treatments.
Conclusions:
- Strategic clinical development plans are essential for 2NME-based oncology regimens.
- Addressing safety, efficacy, and superiority early is key to successful 2NME combination approval.
- The manuscript provides guidance on selecting appropriate settings for these development strategies.
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