NIH/NCI 368: Molecularly Targeted Radiation Therapy for Cancer Treatment

Fast-Track proposals will be accepted.

Direct-to-Phase II will not be accepted.

Number of anticipated awards: 2-3

Budget (total costs, per award):

Phase I: $300,000 for 9 months;

Phase II: $2,000,000 for 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Summary

Targeted radionuclide therapy (TRT) enables personalized cancer treatment by combining the therapeutic effect of radiation therapy with the targeting capability of molecular therapies.  In TRT, a cytotoxic dose of a radioactive isotope is attached to monoclonal antibodies, receptor ligands, or synthetic molecules that target malignant tumor cells selectively. The ability of these molecules to bind specifically to a tumor-associated structure ensures that the tumor gets a lethal dose of radiation, while normal tissue gets only a minimal dose. This minimizes toxicity to normal tissues and can increase therapeutic efficacy (therapeutic index) leading to a reduction of overall treatment costs.

Currently available TRT compounds such as Zevalin and Bexxar have been developed and approved in the United States for use in the treatment of non Hodgkins Lymphoma (NHL).  Although these drugs have shown a response rate of approximately 80%, they have failed to show a survival advantage in patients. Large multicenter trials to study long- term survival are currently underway.  Because these drugs have had modest commercial success to date, private investment in molecularly-targeted radiation pharmaceuticals remains at low levels.  As this class of treatments shows tremendous clinical potential, there is a need to encourage the development of next-generation technologies (see below) for cancers other than NHL, including solid tumors, where the clinical need is most acute.

Project Goals

This contract solicitation seeks to stimulate research, development, and commercialization of innovative TRT techniques that could potentially shorten treatment cycles and reduce toxicity to normal tissues. Proposals addressing the following technology areas are encouraged: new treatment strategies; design, synthesis and evaluation of innovative ligands and radiotracers for TRT; novel radioisotope generators and radioisotope production techniques; dosimetry techniques; new treatment planning strategies facilitating combination of TRT with conventional therapies; and new conjugation chemistries that can link the radioisotopes to targeting agents other than antibodies (e.g. existing small molecule chemotherapeutic drugs) are also encouraged.

The short-term goal of the project is to perform feasibility studies for development and use of possible radiotherapeutics for the treatment of cancer.  The long-term goal of the project is to enable a small business to bring a fully developed TRT compound or TRT-supporting technology to the clinic and eventually to the market.

Phase I Activities and Deliverables

Phase I activities should support the technical feasibility of the innovative approach. Specific activities and deliverables during Phase I should include:

• Proof-of-concept of the conjugation or attachment of the radioisotope to the antibody or other targeting moiety.
• Radiation dosimetry studies in an appropriate small animal model
• Proof-of-concept small animal studies demonstrating an improved therapeutic efficacy and improved therapeutic index, assessment of toxicity to normal tissues, and pharmacokinetic/pharmacodynamic studies utilizing an appropriate animal model.

Phase II Activities and Deliverables

Where cooperation of other vendors or collaborators is critical for implementation of proposed technology, the offeror should provide evidence of such cooperation (through written partnering agreements, or letters of intent to enter into such agreements) as part of the Phase II proposal.

• Specific activities and deliverables during Phase II should include:
• Demonstration of the TRT manufacturing and scale-up scheme
• IND-enabling studies, preferably in consultation with FDA, carried out in a suitable pre-clinical environment.
• When appropriate, demonstration of similar or higher specificity and sensitivity of the technology when compared to other technologies.
• Offerors are encouraged to demonstrate knowledge of appropriate FDA regulations and strategies for securing insurance reimbursement.