A groundbreaking dual-targeting radiopharmaceutical therapy has demonstrated remarkable safety and efficacy in treating advanced cancers, with nearly 90% of patients experiencing tumor shrinkage or disease stabilization in a first-in-human clinical trial. The innovative treatment, which acts like a "smart missile" by simultaneously targeting two vulnerable sites on cancer cells, represents a significant advancement in precision cancer therapy.
Novel Dual-Targeting Approach
The investigational therapy, 177Lu-labeled FAPI-RGD, combines two targeting mechanisms to enhance tumor uptake and therapeutic efficacy across multiple cancer types. Unlike existing radiopharmaceutical therapies that target a single molecular biomarker, this dual-targeting strategy aims to improve treatment precision and potency.
"Radiopharmaceutical therapy is a promising new tool for anti-tumor treatment, and is already used clinically, most notably for prostate cancer and neuroendocrine tumors," said Jialing Xiang, PhD student at Peking Union Medical College Hospital in Beijing, China. "While most existing therapies target a single molecular biomarker, my colleagues and I explored a dual-targeting strategy to simultaneously engage two tumor-associated markers, with the aim of enhancing tumor uptake and therapeutic efficacy across multiple types of cancer."
Clinical Trial Results
The Phase I study enrolled nine patients with advanced adenocarcinomas, including pancreatic, pulmonary, renal, and ovarian cancers. All participants received a single treatment cycle of the investigational agent after baseline uptake was confirmed using ⁶⁸Ga-FAPI-RGD PET/CT imaging.
The treatment demonstrated exceptional tolerability, with no noticeable side effects reported across all patients. The therapy showed strong and lasting uptake in tumors, enabling delivery of high-dose targeted radiation directly to cancer cells. Most significantly, 88.9% of patients responded positively, with their cancer either shrinking or stopping its growth.
Enhanced Quality of Life
Beyond the impressive response rates, patients experienced substantial improvements in quality of life compared to previous treatments. Many reported relief from physical symptoms, including reduced pain, improved appetite, and overall enhanced well-being.
"The beauty of this drug is that it stays in tumors for days, allowing prolonged damage to cancer cells," noted Xiang. "It offers real hope for patients with advanced cancers who have exhausted other treatment options."
Mechanism of Action
The dual-targeting radiopharmaceutical works by binding to two different markers on cancer cells simultaneously, increasing the likelihood of successful tumor targeting. Once attached, the therapy delivers radiation directly to the malignant tissue while the prolonged tumor retention allows for sustained therapeutic effect over several days.
The approach addresses a key limitation of current single-target radiopharmaceutical therapies by providing multiple pathways for tumor engagement, potentially reducing the likelihood of treatment resistance and improving overall efficacy.
Future Development
The promising results from this first-in-human study have paved the way for expanded clinical development. Future prospective trials are planned to optimize dosage regimens for maximum patient benefit, with researchers expressing optimism about the therapy's potential to transform treatment options for patients with advanced cancers.
The findings were presented at the Society of Nuclear Medicine and Molecular Imaging 2025 Annual Meeting, marking a significant milestone in the evolution of targeted radiopharmaceutical therapy. The dual-targeting approach represents a new paradigm in precision oncology, offering hope for patients with limited treatment options.
