ASCO24: J&J's radioligand trial clouded by early patient deaths

Johnson & Johnson's latest venture into the radiopharmaceutical sector has yielded noteworthy results. The company's targeted alpha therapy, JNJ-6420, has shown promising anti-tumor effects in men with metastatic castration-resistant prostate cancer (mCRPC) who have already undergone extensive treatment. These findings are based on early-stage trial data that will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting.

JNJ-6420 targets human kallikrein 2 using an actinium-225 (225Ac)-labeled antibody. The first-in-human Phase I study demonstrated both the potential efficacy and risks associated with this experimental therapy. Among 57 patients who received dose levels of 150 µCi or higher, 45.6% experienced a significant reduction in prostate-specific antigen (PSA) levels by at least half (PSA50), and 14% achieved a reduction of 90% (PSA90). Furthermore, the therapy elicited substantial and lasting biochemical and radiographic responses after just one or two doses. Out of 24 patients with measurable disease at baseline, the objective response rate was 12.5%, which included one complete response and two partial responses.

However, the promising efficacy of JNJ-6420 is tempered by significant treatment-related toxicities. Among the adverse events noted were thrombocytopenia and interstitial lung disease (ILD), with rates of 63.2% and 9%, respectively. Researchers highlighted that all ILD cases occurred at cumulative doses of 500 µCi or higher and before the implementation of pulmonary function monitoring. Overall, 61.4% of patients who received 150 µCi or more experienced Grade 3 or higher treatment-emergent adverse events. These included not only thrombocytopenia and ILD but also anemia, lymphopenia, and leukopenia. Due to these toxicities, nine out of 57 patients (15.8%) discontinued treatment.

The study also reported that four patient deaths were considered related to the treatment, raising concerns about the safety profile of JNJ-6420. These fatalities underscore the risks associated with using high-dose radiopharmaceuticals, particularly in a population that is already heavily pretreated and may have compromised health.

Despite these challenges, Johnson & Johnson's foray into the radiopharmaceutical space is part of a broader trend in the industry. The company joins other pharmaceutical giants like Eli Lilly, which recently entered into a substantial deal with Aktis Oncology valued at up to $1.1 billion. These moves highlight the growing interest and investment in radiopharmaceuticals, a field that is becoming increasingly competitive.

In summary, while JNJ-6420 has shown encouraging anti-tumor efficacy in early-stage trials, its safety profile remains a significant concern. The upcoming ASCO annual meeting will provide a platform for further discussion and analysis of these findings. The high rate of serious adverse events and treatment-related deaths will likely be focal points of these discussions. As Johnson & Johnson continues to navigate the complexities of advancing JNJ-6420, the balance between efficacy and safety will be crucial in determining the future of this promising but risky therapeutic approach.