KEY TAKEAWAYS
- The phase 1 trial aimed to assess IMDs in RCC for safety, efficacy insights, and personalized treatment plans for pts with RCC.
- The endpoints of the study are measuring the safety and feasibility.
- IMDs in RCC will prospectively show promising treatment optimization and accelerate drug development.
Multiple therapeutic options are available for renal cell carcinoma (RCC), yet no personalized biomarkers exist that can guide optimal treatment for individual treatment. This study develops implantable microdevices (IMD) that can be placed within a target tumor using a standard small-gauge interventional needle under imaging guidance.
The IMDs deliver spatially segregated microdoses of up to 20 different drugs and/or combinations over multiple days and are then retrieved surgically with surrounding tissue. This allows for the assessment of tumor response to multiple drugs in vivo within the native tumor microenvironment without exposing the patient to systemic drug toxicity.
By directly analyzing the tumor’s reaction to various treatments, this method offers a more precise and individualized approach to cancer therapy, potentially leading to better patient outcomes.
Wenxin Xu and the team are conducting a trial to evaluate the safety and feasibility of IMD implantation in RCC tumors and subsequent collection of drug response data on targeted, cytotoxic, and immune-modulatory agents and aim to provide critical insights into the effectiveness of various therapies paving the way for developing personalized treatment plans for patients (pts) with RCC.
Eligible pts diagnosed with suspected or confirmed RCC and scheduled for standard surgical resection of their primary tumor or metastasis are enrolled in the study. Precisely 3 days prior to their scheduled surgery, one or more IMDs are percutaneously implanted into the tumor under CT guidance.
After nephrectomy or excision of the metastasis, the microdevices, along with surrounding tumor tissue, are surgically removed en bloc. Subsequently, the tissue is processed by fixation, embedding, and sectioning.
The tumor/IMD cross-sections undergo comprehensive analysis to evaluate the effects of each spatially separate treatment using various techniques. These include immunohistochemistry to assess proliferation and pathway markers, spatial immune profiling utilizing a panel of 25 tumor microenvironment markers, and spatial transcriptomics. Following surgery, pts proceed with standard-of-care systemic treatment based on their oncologist’s recommendation.
To date, 5 pts have been enrolled in the trial, with a total of 16 IMDs successfully implanted. Enrollment is ongoing, with a planned total of 20 pts. The study’s success criteria include meeting both safety and feasibility endpoints. Safety is defined as experiencing two or fewer safety failures out of the 20 enrolled pts. Feasibility is defined as achieving successful implantation and retrieval of interpretable data from at least 16 out of the 20 pts.
Analysis of the IMDs aims to elucidate spatially segregated drug effects within the tumor microenvironment, including impacts on tumor cell death, immune cell activation, and variations in drug sensitivity among treatments and pts. These findings promise to enhance our understanding of personalized treatment approaches for RCC, potentially leading to improved outcomes for pts undergoing surgical resection.
Implantation of microdevices in RCC tumors is expected to be a useful prospective approach to treatment improvement, selection, and accelerating drug development. Trial enrollment is still ongoing.
The trial was sponsored by Wenxin Xu, Dana-Farber Cancer Institute.
Source: https://kcrs.kidneycan.org/wp-content/uploads/2024/06/KCRS24-Abstract-Book-6.27.24.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT05700461
Xu W, Bhagavatula S, Steiner C, et al. (2024). “Pilot study of an implantable microdevice for in vivo evaluation of drug response in renal cell carcinoma (NCT05700461).” Presented at KCRS 2024 (Abstract 29).
