DiBardino Outlines Phase 2 CONVERGE Trial Design of Radioenhancer in NSCLC

David DiBardino, MD, discussed the design of the phase 2 CONVERGE trial (NCT06667908), which is evaluating the radioenhancer NBTXR3 (JNJ-1900), a hafnium compound, in patients with locally advanced non–small cell lung cancer (NSCLC).

DiBardino described CONVERGE as a safety and efficacy signal–finding study rather than a translational effort to deliver an antitumor asset. Its end points include safety, feasibility, and efficacy vs a control arm.

He emphasized the unmet need. For patients with locally advanced NSCLC who are not eligible for surgery, standard care is concurrent chemoradiation for about 6 weeks followed by roughly a year of durvalumab (Imfinzi). Even with this regimen, the objective response rate in clinical trials is about 30%, and 2-year survival is roughly 50% to 60%. That means about 70% of patients do not have an objective response. Because the radiation dose, about 60 Gy, is near the maximum tolerable, escalating it is not a realistic way to improve efficacy.

CONVERGE instead seeks to make existing radiation work better. The hafnium compound increases reactive oxygen species and radiation-mediated cell death beyond what radiation achieves through water, the molecule it typically relies on in tumors. It can be injected into any identifiable tumor, including the primary lung lesion and mediastinal lymph nodes.

The trial has 2 parts. Part A, a 7-patient run-in that was recently presented, focused on procedural standardization, feasibility, and reproducibility. The team built the procedure manual from scratch, and success was defined as the injection being delivered to and retained in the intended location. The full study will enroll 120 patients, randomized in equal thirds to chemoradiation and durvalumab alone, the same regimen plus a single injection of a lower dose into all injectable tumors, or the same regimen plus a higher dose.

This design will allow comparison of safety signals across the 3 arms and hypothesis generation on efficacy. If the run-in confirms reproducibility, the larger study will shift from refining the procedure to evaluating those outcomes.