Through this funding opportunity announcement (FOA), the National Cancer Institute (NCI) requests applications for PDX (patient-derived xenografts) Development and Trial Centers (PDTCs) to serve as the laboratory research units of the PDX Development and Trial Centers Research Network (PDXNet). The PDXNet is a National Cancer Institute (NCI) program established to coordinate collaborative, large-scale development and pre-clinical testing of targeted therapeutic agents in patient-derived models to advance the vision of cancer precision medicine. PDTCs will interact with a PDXNet Data Commons and Coordinating Center (PDCCC) to be supported by a companion FOA, (RFA-CA-22-013) in a collaborative network.
The main goals for PDTCs include:
- Develop and implement mechanism-based preclinical trials of drug combinations in large sets of molecularly characterized PDXs to advance cancer precision medicine through the therapeutic development of these agents, with a focus on NCI-Investigational New Drug (IND) agents,
- Provide evidence-based recommendations for early phase clinical trials to be conducted in NCI clinical trial networks by identifying agent combinations that produce in vivo evidence of deep and durable responses of PDX models to the therapeutic interventions,
- Develop and characterize new PDX models to share with the NCI Patient-Derived Models Repository (PDMR) that fill identified resource gaps in the PDMR collection. This includes PDX models from patients with clinical drug resistance, models obtained from racial/ethnic minority populations, and models of rare cancers,
- Engage collaboratively as a network to develop and apply metrics for preclinical in vivo drug response that improves the value of PDX drug response data in predicting clinical outcomes,
- Advance the understanding of therapeutic outcome disparities by race/ethnicity to ensure that early phase clinical trials are well equipped to support diverse and equitable recruitment, and
- Devise procedures and platforms to make preclinical PDX data broadly available to researchers across the cancer community, using PDTCs’ and NCI’s mutually agreed upon standards.
This FOA is a reissuance of RFA-CA-17-003 and RFA-CA-17-032 and incorporates objectives of both the previous FOAs. PDXNet will encompass up to five PDTCs (to be supported by this FOA) and a single PDX Data Commons and Coordinating Center (PDCCC) (to be supported by a companion RFA-CA 22-013). Collaboration between PDXNet and the NCI Patient-Derived Models Repository (PDMR) at the Frederick National Laboratory for Cancer Research (FNLCR) will be required as part of this FOA. PDTCs will be required to collaborate with PDMR in several areas related to the goals of the program, including the development of optimized standard procedures, and in sharing of PDX models.
Deadlines:
- Letter of Intent Due Date(s): 30 days prior to the application due date
- Application Due Date: November 1, 2022
RFA-CA-22-012 Expiration Date November 02, 2022
Application budgets must not exceed $810,000 per year in direct costs.
Project period of 5 years is required.