CPRIT Awards: Dr. Asal Rahimi & Dr. Raquibul Hannan

UT Southwestern’s Department of Radiation Oncology has recently won two Cancer Prevention and Research Institute of Texas (CPRIT) awards. The recipients are Raquibul Hannan, M.D., Ph.D., Professor of Radiation Oncology and Chief of Genitourinary Radiation Oncology Service, and Asal Rahimi, M.D., M.S., Professor of Radiation Oncology, Associate Vice Chair for Program Development, Medical Director of the SCCC Clinical Research Office, and Chief of Breast Radiation Oncology Service.

Co-investigators on Dr. Hannan’s team are Laurentiu Pop, M.D., Assistant Professor of Radiation Oncology; Zhijian Chen, Ph.D., Professor of Molecular Biology; Payal Kapur, M.D., Professor of Pathology and Urology; Tao Wang, Ph.D., Associate Professor of Public Health; Lindsay Cowell, Ph.D., Associate Professor of Public Health; Kiyoshi Ariizumi, Ph.D., Professor of Dermatology; Chul Ahn, Ph.D., Professor of Public Health; and Faya Zhang, Ph.D., research scientist.

Dr. Rahimi’s co-principal investigator is Basak Dogan, M.D., Professor of Radiology and Director of Breast Imaging Research. Other co-investigators on Dr. Rahimi’s team include Prasanna Alluri, M.D., Ph.D., Assistant Professor of Radiation Oncology; Marilyn Leitch, M.D., Professor of Surgery; Yu-Lun Liu, Ph.D., Assistant Professor of Public Health; and Sunati Sahoo, M.D., Professor of Pathology.

Dr. Hannan’s award will go toward the expansion of the RCC SPORE-supported SPARK clinical trial, led by Dr. Hannan, Hans Hammers, M.D., Ph.D., Professor of Internal Medicine; and James Brugarolas, M.D., Ph.D., Professor of Internal Medicine and Director of the Kidney Cancer Program. The trial is focused on patients with metastatic kidney cancer. This study looks at the impact of personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR®), an advanced form of stereotactic ablative radiotherapy (SAbR), when used in tandem with a drug called IMSA101, a STING (stimulator of interferon genes protein) agonist. This is a novel drug discovered by Dr. Zhijian Chen and his group, which, when combined with PULSAR simultaneously, activates both the innate and adaptive immune systems, ultimately maximizing the immune response. More specifically, this trial will use PULSAR to stimulate antigen presentation, followed by IMSA101 administration to induce innate immune activation. Together with immune checkpoint inhibitory (ICI) immunotherapy, these two mechanisms will comprehensively trigger the immune system to initiate an anti-tumor response.

This study will include a feasibility phase two clinical trial, followed by analysis of the induced anti-tumor immune response through tissue analysis and immune-PET. Importantly, many patients do not respond to ICIs alone and instead experience side effects, as these drugs primarily target the amplification of the preexisting immune response but may be ineffective in the absence of preexisting anti-tumor immunity where there may be nothing to amplify. Consequently, Dr. Hannan and his team’s research holds great potential to address this unmet medical need to improve the response to ICIs and cure more patients.

“The SPARK trial is expected to reignite patients’ immune systems against their kidney cancer,” Dr. Hannan says. “If successful, this trial will provide the necessary foundation for a larger phase three trial in the future.”

Drs. Rahimi and Dogan’s award supports a clinical trial aimed at showing the efficacy of using single-fraction preoperative SAbR to eradicate early-stage breast cancer with radiation. Pathologic complete response rates will be evaluated to determine this approach’s efficacy. The radiologic endpoints of this study led by Dr. Dogan will also examine microbubble contrast-enhanced ultrasound as a method for conducting nonsurgical sentinel lymph node biopsies. In addition to MRI, a novel technique, optoacoustic imaging, will be used to evaluate changes to the tumor microenvironment and treatment response. Dr. Alluri will lead the translational studies for this clinical trial, which are focused on understanding the molecular determinants of response to preoperative radiation in ER+ breast cancer patients.

Importantly, results from this trial will pave the way toward nonsurgical management of patients with early-stage breast cancer. Furthermore, if this study yields favorable results, it could offer patients the option to consider a nonoperative treatment technique of ablative radiation for early-stage breast cancer, instead of the current standard-of-care treatment, which includes lumpectomy surgery, sentinel lymph node mapping, and one to four weeks of breast radiation. Ultimately, this may enhance patient quality of life by minimizing recovery time and clinic visits, while improving treatment convenience for patients.

The phase one single-fraction preoperative ablative SAbR trial for early-stage breast cancer has been completed for enrollment, with groundbreaking preliminary results that were presented at the Late Breaking Session at the 2023 ASTRO meeting. In that trial, Dr. Rahimi and her group showed up to a 93% pathologic complete/near response of tumors with single-fraction radiation. The phase two study is anticipated to open toward the end of 2024.

“This trial has the potential to establish that definitive radiation may cure early-stage breast cancer,” Dr. Rahimi says. “Ultimately, we need to continue advancing medicine and science with new ideas and develop new ways that will allow our patients and humanity to remain high functioning during cancer treatments, while obtaining high cure rates. We need to find ways to define cancer, and not let cancer define our lives.”