Radiopharm Theranostics (ASX: RAD; Nasdaq: RADX), headquartered in Sydney, Australia and Malvern, Pennsylvania, reported the first confirmed clinical response with its PD-L1-targeted radiotherapeutic RAD204 (¹⁷⁷Lu-RAD204), providing early evidence that the approach may retain activity in advanced solid tumors after progression on immune checkpoint inhibitors. The findings come from an ongoing first-in-human Phase I dose-escalation study and support continued escalation of a program designed to exploit PD-L1 as a tumor-targeting marker rather than as a therapeutic checkpoint.
The updated data include one RECIST-confirmed partial response in a patient enrolled in the third dose cohort, with tumor shrinkage meeting response criteria after the second treatment cycle and remaining confirmed through four cycles. The patient has remained progression-free for more than seven months. A second patient in the same cohort demonstrated an initial 7% reduction in target lesions after one treatment cycle and remains on study. Across the first three dose cohorts, Radiopharm reported no dose-limiting toxicities or treatment-related serious adverse events, allowing continued dose escalation.
The Phase I trial (NCT06305962) is evaluating escalating doses of ¹⁷⁷Lu-RAD204 in patients with metastatic solid tumors, including non-small cell and small cell lung cancer, triple-negative breast cancer, melanoma, head and neck squamous cell carcinoma, and endometrial cancer whose disease has progressed following prior immunotherapy. The primary objective is to establish a recommended Phase II dose while characterizing safety, dosimetry and pharmacokinetics. The efficacy findings remain preliminary, reflecting only two treated patients in the current cohort, and no overall response rate or mature durability data have yet been reported.
RAD204 differs fundamentally from immune checkpoint inhibitors by using PD-L1 as a delivery target rather than attempting to restore T-cell function. The nanobody binds PD-L1 expressed on tumor cells and delivers the beta-emitting radioisotope lutetium-177 directly to the tumor, enabling targeted radiation even in cancers that have already developed resistance to PD-1 or PD-L1 blockade. If successful, the strategy could allow persistent PD-L1 expression—a mechanism tumors use to evade immune attack—to instead become a therapeutic vulnerability.