New lung cancer treatment targets resistant tumors

Stage 3 non-small cell lung cancer (NSCLC) often resists standard treatment, leaving many patients with tumors that don’t shrink despite aggressive chemotherapy, radiation, and immunotherapy. Even when patients complete a year of Imfinzi (durvalumab) after initial therapy, roughly 70% see no meaningful tumor reduction. Researchers are now testing a new approach: injecting a radiation-boosting compound directly into tumors to enhance the effectiveness of existing treatments.

The phase 2 CONVERGE trial is evaluating JNJ-1900 (NBTXR3), a medicine made from tiny particles of hafnium oxide. Unlike traditional radiation, which relies on water within tumors to damage cancer cells, the hafnium compound amplifies that damage, potentially making radiation more effective without increasing the dose. Patients already receive near the body’s safe radiation limit of 60 gray, so finding ways to improve outcomes without added toxicity is critical.

Why standard treatment fails for many patients

Dr. David DiBardino, an interventional pulmonologist at the University of Pennsylvania, explains that only about 30% of patients in clinical trials experience an objective response—meaning their tumors shrink by a measurable amount on scans. The remaining 70% endure treatment side effects without benefit. Radiation, while effective against NSCLC, hits a biological ceiling. “Raising the dose isn’t an option,” DiBardino says. “We’re already at the limit of what the body can handle.”

Immunotherapy, which has transformed outcomes for some patients with NSCLC and melanoma, also falls short for many. Both cancers often carry high numbers of genetic mutations, which can signal the immune system to attack tumors. Yet even with this advantage, responses remain inconsistent. “We know immunotherapy works spectacularly for certain patients,” DiBardino notes. “But why it doesn’t work for others is still unclear.”

Researchers are now exploring whether combining immunotherapy with targeted intratumoral therapies, like JNJ-1900, could bridge that gap. Early melanoma studies suggest direct tumor injections may help, though not all approaches have succeeded in larger trials. Precision in delivery appears key: some failed phase 3 trials may have struggled with inconsistent injection techniques, leading to uneven distribution of the medicine.

Lessons from melanoma and the challenges ahead

Intratumoral therapy isn’t new. Melanoma research pioneered the approach, with some injected treatments now approved as standalone or combination therapies. However, not all have translated to broader success. DiBardino points to phase 1 and 2 trials where promising early results faded in phase 3 testing. “The instructions for injecting tumors may not have been precise enough,” he says. “If the medicine doesn’t reliably reach the tumor or stays there long enough, the effect can be lost.”

What the CONVERGE trial could reveal

The CONVERGE trial builds on decades of fragmented research, testing whether hafnium oxide can make radiation more potent when delivered directly to tumors. If successful, it could offer a new tool for the 30% of patients who currently don’t benefit from standard therapy. Yet questions remain: Will the medicine stay localized? Can it be safely combined with immunotherapy? And how will it change the way lung cancer teams work together?

Prior research on intratumoral therapy in lung cancer

Intratumoral therapy has been explored in lung cancer through several dozen small pilot studies. These trials involved injecting tumors with various treatments and included diverse patient groups. The studies used basic injection methods and produced inconsistent results, which is typical for early-stage research.