Accelerating Cancer Drug Development

Despite increases in drug development expenditures in the public and private sectors during the 1990s, the number of new agents reaching human clinical trial has been decreasing. Even when compounds proceed to clinical testing, they often fail because of unexpected toxicities or lack of efficacy. The pathway from discovery of promising agents to delivery in the oncology clinic, though multifaceted and complex, may change due to improvements in our understanding of drug targeting at the molecular level. Modern drug development techniques that employ imaging and other advances also make foreseeable the arrival of screening tools that could, early in the pathway, predict therapeutic or toxic activity in humans. Such changes should shorten the amount of time it takes to bring useful new anticancer drugs to the patients who need them.

The following improvements in the use of DCTD resources have been made in the past year to accelerate drug development:

• DCTD and the Center for Cancer Research (CCR) have established a formal partnership to enhance preclinical and clinical drug testing
  • A joint pipeline of new agents is now being actively managed by DCTD and CCR
    • Decisions about what agents to develop are being made by a newly established joint development committee
    • Molecules entering the pipeline will be managed by teams with members from both DCTD and CCR
    • Joint drug development teams will be guided by a new DCTD Developmental Therapeutics Project Management Office, bringing a business-focused approach to tracking the progress of agents from discovery through early phase clinical trial
  • Together, DCTD and CCR investigators will utilize the recently announced Food and Drug Administration exploratory IND guidance to facilitate testing of targeted therapies in patients earlier in the drug development process so that informed decisions to proceed with or stop development can be made before expensive bulk drug formulation occurs. These studies will also take advantage of new advances in molecular imaging, which can help detect whether an agent being tested is reaching its target and having the desired effect.
    • Extramural drug developers, for the first time, will be offered opportunities to utilize CCR resources for clinical trial support. This mechanism will be employed for novel molecules or high-priority targets.
• The DCTD Developmental Therapeutics Project Management Office will also lend project management assistance to advance the evaluation of targeted therapies being studied jointly by the DCTD Developmental Therapeutics and Cancer Therapy Evaluation Programs
• DCTD has initiated a new molecular toxicology laboratory that will develop novel approaches to toxicologic prediction using normal human tissues. This is concurrent with the new commitment by DCTD and CCR to combine resources to focus on developing predictive, preclinical molecular pharmacodynamic assays. These assays will support the clinical development of agents for which NCI holds the IND.
• The division has also expanded its capabilities to develop and standardize diagnostic imaging biomarkers in addition to pharmacodynamic assays. These processes will be aided by the development of new imaging tools and agents that can track molecular events in tumors and normal tissues. Once completed, the portfolio of biomarkers and assays will be made available to all interested cancer researchers. DCTD has identified several resources to help achieve this goal. Chief among them is the establishment by DCTD and CCR of a new National Clinical Target Validation Laboratory (NCTVL). This laboratory will develop and authenticate pharmacodynamic assays well in advance of human studies, so that they can be used in early phase trials to provide information about the safety and efficacy of the entities being tested.