How Might a Novel Radioenhancer Impact Stage III Unresectable NSCLC Care?

JNJ-1900, an investigational nanoparticle radioenhancer, represents a “fantastic opportunity” to improve the standard of care in stage III unresectable non–small cell lung cancer (NSCLC), according to Benjamin Cooper, MD.

Cooper, an associate professor in the Department of Radiation Oncology at NYU Grossman School of Medicine, site director of Radiation Oncology at Perlmutter Cancer Center 34th campus, and director of Proton Therapy Services Radiation Oncology, spoke with CancerNetwork^® about findings from the phase 2 CONVERGE trial (NCT06667908) that he presented in a poster session at the 2026 European Lung Cancer Congress. Data from the run-in portion of the study revealed that intratumoral therapy with JNJ-1900 was feasible and produced initial responses across a small cohort of patients with stage III disease. These observations supported continued investigation of the agent in part 2 of the study, which is currently enrolling patients.

During the conversation, Cooper broke down the rationale for evaluating JNJ-1900 in this treatment setting while highlighting the limitations associated with concurrent chemoradiation, the current standard of care. Additionally, he detailed updated safety and efficacy results from the trial and described the potential utility of radioenhancers in NSCLC and other disease types.

CancerNetwork: What was the rationale for assessing JNJ-1900, a novel radioenhancer, among patients with stage III unresectable NSCLC?

Cooper: At ELCC, we presented the early lead-in [data] to what is eventually going to be a randomized phase 2 trial of a novel intratumoral radioenhancer—JNJ-1900—with chemoradiation and consolidated immunotherapy for stage III unresectable NSCLC. Concurrent chemoradiation is the standard of care for patients with unresectable NSCLC. Unfortunately, only about 45% to 50% of these patients achieve an objective response, and local regional failure rates remain high. In order to try to improve our overall response rate, as well as decrease the risk of local regional failure, we are testing JNJ-1900, which is a first-in-class nanoparticle radioenhancer. This is injected intratumorally, so either through transthoracic needle or, as is the case for many of these patients, through a bronchoscopic intervention. JNJ-1900 is thought to work because it is a hafnium oxide core, which is a high electron density particle; the radiation causes more reactive oxygen species and causes more cell death in the tumor and the lymph nodes themselves. This can be beneficial to prevent either the tumor from coming back or persisting after chemoradiation.

Historically, why has local disease control remained a key challenge in stage III NSCLC?

Many patients with stage III unresectable NSCLC often have large tumors and central tumors with multiple lymph nodes involved. For this reason, the larger the tumor is, the less likely radiation and chemotherapy are to control the disease locally. This is especially true with central disease, where you can’t escalate the radiation dose as high as you would want because of the surrounding organs at risk, such as the heart and the esophagus. This is in contrast to stage I lung cancer, where stereotactic body radiotherapy [SBRT] can be given to very high doses and provides excellent local control these larger tumors. The location of these tumors makes those types of doses impossible and unsafe.

What do preliminary findings show about the early clinical efficacy of JNJ-1900 in this patient population?

The 2 cohorts that were presented at ELCC were Cohort A and Cohort B; these were 2 safety cohort of patients to see [what happens] when you inject 22% of the volume and 33% of the volume, respectively, into the lymph node. [We wanted to see] if it was safe and how these patients would respond.

In those 7 patients—3 patients got 22%, 4 patients got 33%—a majority were male patients, and the majority were former smokers. We saw an overall response rate of 71%, which was quite good at the first time point. There will be further data presented that will potentially show future time points, which we expect to show a sustained and hopefully improved overall response rate.

How does the safety profile of JNJ-1900 compare with other standard therapies? How are notable adverse effects managed?

All the injections were completed per plan, so there were no issues. Specifically, there was 1 patient who had a procedure-related adverse event. One had some hypokalemia or decreased calcium that was grade 1, so not so significant. One had some non-cardiac chest pain after the procedure. Otherwise, the [adverse] effects that we saw were very similar to the [adverse] effects we see with concurrent chemoradiation, which is mostly fatigue, esophagitis, and some issues with blood counts.

What are the next steps for evaluating JNJ-1900 in stage III NSCLC or other settings?

Part 2 [of the trial] is now open. This is a 1:1:1 randomized trial where we hope to enroll 120 patients, with 40 patients in each arm. Arm A is going to [have] 22% of the volume injected. Arm B [will receive] a slightly higher dose of the radiosensitizer, which is 33% [of the tumor volume]. Then, Arm C is going to be standard of care so we can see what the added benefit of JNJ-1900 is. Potentially, at the 2 different dose levels, there [may be] a dose response to the benefit.

What do you hope others take away from this study?

I would love for more centers to try to get this [treatment] open at their institution. It’s a fantastic opportunity to try to improve a standard of care that hasn’t budged much in the last decade or so. It’s unique in that this is a radiosensitizer that is injected intratumorally. There’s been a long history of either radiosensitizers, which make the radiation work better, or radioprotectors, which protect the normal tissues. But one of the main limitations for both strategies has been that most things that sensitize the radiation in the tumor also sensitize the radiation in the normal tissue. Patients would have increased [adverse] effects. Conversely, radioprotectors, things that would make the radiation hurt the organs at risk less, would sometimes make it so the tumors were controlled less. [JNJ-1900] has the advantage of being directed into the tumor with only a local effect in the tumor, and we may have an opportunity to use these radiosensitizers in NSCLC as well as other diseases.

Reference

Cooper BT, Bradley JD, Patel S, et al. Novel intratumoral radioenhancer (JNJ-1900) with chemoradiation and consolidative immunotherapy for stage III unresectable non-small cell lung cancer (NSCLC): early outcomes from the phase II CONVERGE study. Presented at the 2026 European Lung Cancer Congress; March 25-28, 2026; Copenhagen, Denmark. Abstract 297P.