NCI Experimental Therapeutics Program (NExT)

DCTD and the Center for Cancer Research (CCR) are working in close collaboration to reinvigorate cancer drug development at NCI. Through a new, joint early therapeutics development program, extramural and intramural teams have prioritized a pipeline of NCI-driven targeted therapeutics for development. This program, called the NCI Experimental Therapeutics Program (NExT), combines the strengths of DCTD’s extensive expertise in anticancer drug development with CCR’s dynamic in-house research and its location within new state-of-the-art facilities at the NIH Clinical Research Center. This collaboration will also utilize a recent guidance from the U.S. Food and Drug Administration concerning exploratory studies of investigational new drugs.

Clinical trials performed using an exploratory investigational new drug (IND) will facilitate targeted therapies entering early phase evaluation where the target can be carefully monitored. The goal of this new guidance is to safely shorten the timeline for drug development. As part of the DCTD-CCR collaboration, novel agents for high-priority targets originating from academic and other extramural researchers will be eligible to take advantage of intramural resources.

Exploratory IND studies are ideal, as well, for imaging and other advanced technology applications aimed at developing clinically relevant assays of bio-markers that could help predict whether later-stage trials are likely to be successful. Biomarker assays can also assess the efficacy, mechanism of action, and toxicity of promising treatments. DCTD is also improving its capabilities to develop and validate pharmacodynamic markers. The division is developing standardized operating procedures for handling human tissue specimens and for pharmacodynamic assays. One major goal of this program is to incorporate molecular imaging techniques routinely into early therapeutics development; in particular, there will be a special emphasis on the development of novel imaging probes for monitoring new drug targeting to tumors and for determining the therapeutic benefit of the targeted therapy.

The goal is to produce a diverse portfolio of pharmacodynamic assays and imaging tools that are in the public domain. These complex tasks are time-consuming and expensive, and NCI is well suited to take on this enterprise. It is anticipated that this investment will reap many benefits by making a library of new molecular tools available to all researchers in the cancer research community to assess new targeted drugs and diagnostics.

These efforts also support an NCI-wide priority to better integrate preclinical and clinical research. In addition to partnering with intramural researchers in CCR, DCTD is working to link preclinical and clinical resources seamlessly within the division. This will support extramural trials of targeted therapies and foster better assimilation of molecular imaging and radiation techniques into therapeutics development. Teams of experts across NCI will unite to form integrated drug development teams. A joint CCR-DCTD drug development committee will oversee these teams, determine resource priorities, assess agent progress, identify gaps in the portfolio particularly suited to NCI drug development efforts, and evaluate new compounds for inclusion in the pipeline.

The following improvements in the use of DCTD resources were made to accelerate drug development:

• DCTD and CCR have established NExT to enhance pre-clinical 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.

Additional Information is available in a January 2006 Press Release and in the FDA Guidance.