NExT Resources

Discovery

Overview

The Chemical Biology Consortium (CBC) is the discovery engine of the NExT Program. Established in 2009, NCI’s CBC was designed to be a flexible network of scientists working to increase the flow of early-stage cancer drug candidates into the NExT development pipeline. The CBC network currently has 18 research and development centers, including 12 academic and non-profit institutes, 5 Contract Research Organizations (CRO) and the Early Therapeutics Branch from NCATS. Each center possesses unique resources to advance early stage drug discovery projects through to the clinical candidate stage.

In addition to the CBC, the Developmental Therapeutics Program (DTP) supplements the Discovery stages by providing resources (candidate selection and IND enabling studies) needed to facilitate the preclinical development to first-in-human studies.

The program is also complemented by both internal activities at the Frederick National Laboratories for Cancer Research (FNLCR) and the Center for Cancer Research’s (CCR) dynamic in-house research capabilities.

Chemical Biology Consortium (CBC)

The Chemical Biology Consortium (CBC) in the NCI Experimental Therapeutics (NExT) Program brings together chemical biologists and molecular oncologists from government, industry, and academia to address unmet needs in therapeutic oncology. Members of the consortium contribute their expertise and lab capabilities with high throughput screening, structural biology, medicinal chemistry, compound profiling, cancer cell biology, and animal models for oncology to advance early-stage drug discovery projects to the selection of developmental clinical candidates. Through the CBC, and with the interactions among the various Participants, the NCI’s drug discovery and development pipeline is active from target identification through proof-of-concept clinical trials.

The CBC operates as a collaborative network of 17 Institutes (managed as subcontractors by Frederick National Laboratory for Cancer Research) and 1 partner NIH institute NCATS Early Therapeutic Branch. Drug discovery expertise and dedicated scientists are provided from a wide range of disciplines who together support the advancement of NExT discovery projects and provide scientific leadership to project teams. With a blend of premier universities, non-profit research institutes, contract research organizations (CROs), and government agencies, the CBC offers a complete set of technologies to facilitate the successful progression of discovery projects.

Enlarge

Development

Overview

For more than 50 years the Developmental Therapeutics Program (DTP) at NCI has successfully guided late-stage preclinical drug candidates through the final steps of development to first-in-human studies. DTP has been involved in the discovery or development of more than 70% of the anticancer therapeutics on the market today. The Cancer Therapy Evaluation Program (CTEP) houses NCI’s primary program for clinical evaluation of new anticancer treatments, and provides and tracks experimental agents for clinical trials run by other NCI branches.

Both DTP and CTEP will provide integrated support to move NExT drug discovery and development projects from preclinical to clinical development.

CTEP

The Cancer Therapy Evaluation Program (CTEP) is responsible, within the Division of Cancer Treatment and Diagnosis (DCTD), for coordinating the largest, publicly funded oncology clinical trials organization in the world. CTEP has more than 900 active trials enrolling more than 20,000 study participants annually, nearly 250 grants and cooperative agreements, and about 100 investigational new drugs (INDs). CTEP's staff of almost 60 talented physicians, scientists, pharmacists, nurses, and regulatory specialists, assisted by multiple government contractors, work diligently to assure the safe, efficient, and ethical conduct of this complex research enterprise. CTEP-sponsored research spans Phase I through III trials of all cancer types and treatment modalities — chemotherapy, targeted agents, immunotherapy, radiation, and surgery.

Imaging

The DCTD’s Cancer Imaging Program (CIP) is an innovative program that encourages coordination and collaboration among experts in basic, translational, and clinical research to advance the understanding of cancer imaging and to create better diagnosis and treatment options for patients. CIP is catalyzing the development of molecular and functional imaging that visualizes the physiological, cellular, or molecular processes in living tissues in real time. In vivo molecular imaging elucidates how targets integrate into the complex systems of tumor biology and allows noninvasive treatment monitoring. CIP plays a critical role in the activities of the NCI, contributing to the integration of imaging with emerging technologies such as nanotechnology, proteomics, and HTS.

To meet the need for greater access to imaging facilities for clinical trials conducted in the NIH Clinical Center, the NCI Molecular Imaging Clinic was established by the collaborative efforts of DCTD, CCR, and the NIH Clinical Center. An analogous facility, the NCI-Frederic Small Animal Imaging Program was established in October 2006 to provide NCI Investigators with a state-of-the-art in vivo imaging facility. Capabilities include optical imaging, ultrasound, magnetic resonance imaging, positron emission tomography, and access to a range of appropriate contrast agents. A licensed radiopharmacy in Frederick can prepare investigational radiopharmaceuticals for clinical trials in the Molecular Imaging Clinic.

Imaging Drugs can be integrated into NExT projects in a variety of ways

• New chemical entities being investigated or developed for eventual clinical use as imaging agents. Potential examples:
  • An agent that outlines tumors intraoperatively so that resection can be more complete
  • An agent that diagnoses cancer or evaluates response to interventional therapy
• Labeled therapeutic agent, to be used pre-clinically or clinically.
  • Investigate mechanism of action
  • Evaluate pharmacokinetics and biodistribution of the therapeutic agent at microdose levels or at therapeutic dose
• Companion diagnostic for a specific therapeutic agent to be used to select patients for that specific therapeutic, for example an imaging probe as a companion to a therapeutic directed at the same target.

Pharmacodynamic Biomarkers

Pharmacodynamic (PD) biomarkers are molecular indicators of drug effect on the target in an organism. A PD biomarker can be used to examine the link between drug regimen, target effect, and biological tumor response. Coupling new drug development with focused PD biomarker measurements provides critical data to make informed, early go/no-go decisions, to select rational combinations of targeted agents, and to optimize schedules of combination drug regimens. Use of PD endpoints also enhances the rationality and hypothesis-testing power throughout drug development, from selection of lead compounds in preclinical models to first-in-human trials. Given these critical roles in delivering targeted therapy, the introduction of validated and reliable clinical PD assays is warranted in drug development.

Two biomarker programs, Imaging and Clinical Assay Laboratories, have been set up within the DCTD to provide PD biomarker assay support for NExT drug development projects. The goal of the two programs is to develop assays that will provide robust and accurate measurements of drug effects in patient specimens using the same principles routinely applied to clinical diagnostic tests.