ASCO: J&J's radioligand spurs responses, but 4 deaths mar early results

Johnson & Johnson’s radiopharmaceutical spurred “profound and durable” responses, however, four patient deaths in the early-stage trial marred the results.

JNJ-6420 is an anti-hK2 antibody-based targeted radioligand therapy that's designed to deliver a high-energy, short-range alpha-particle emitter to prostate cancer cells. The first-in-human study tested the radiopharmaceutical in patients with metastatic castration-resistant prostate cancer who have previously received at least one prior androgen receptor pathway inhibitor. The results are to be presented next week at the American Society of Clinical Oncology conference.

The goal of the phase 1 dose-escalation study was to demonstrate the drug's safety and to find a dose to move into phase 2. In one trial group, 37 patients were on a fixed dosing starting schedule, receiving between 50 μCi and up to 300 μCi. Twenty-nine patients in the other trial group were capped at a cumulative 500-μCi dose.

As of the Jan. 5 data cutoff, 64 patients had received at least one dose of JNJ-6420, with safety data being recorded for 57 patients who had received 150 μCi. Of these patients, 35, or 61%, experienced grade 3 or higher treatment-emergent adverse events (TEAEs), and 21, or 37%, had a serious TEAE. Almost all patients experienced some sort of TEAE.

There were four deaths due to TEAEs, which were associated with repeated dosing of JNJ-6420. The full data set linked two of the deaths to interstitial lung disease (ILD), one to respiratory failure related to COVID-19 and one to decreased appetite/hypotension.

ILD is a common adverse event in oncology treatment, particularly for antibody-drug conjugates. The condition causes progressive scarring of lung tissue. The deaths related to ILD occurred in patients who had received cumulative doses greater than or equal to 750 μCi.

The abstract noted cases of thrombocytopenia (low platelet count) in 63% of the reported TEAEs and ILD in 9%. The cases of ILD all occurred in patients who had received cumulative doses of greater than or equal to 500 μCi prior to the implementation of pulmonary function surveillance.

To address the risk of ILD and thrombocytopenia, the study investigators are recommending a cumulative dose cap and an adaptive dose schedule. Evaluation of adaptive dosing is ongoing.  

Other common TEAEs in the study included anemia and two conditions related to low white blood cells, lymphopenia and leukopenia. Nine patients discontinued treatment.

As for the responses, the data showed a reported PSA50 rate of 45.6%. This is a measure of prostatic-specific antigen, which is a key biomarker in prostate cancer. A PSA response is associated with prolonged overall survival.

JNJ-6420 spurred one complete response, two partial responses and three confirmed objective responses.

There were “prolonged clinical, biochemical, and radiographic responses” in patients who received doses of 150 μCi and higher, according to the abstract. Durable responses were also noted in patients who had received JNJ-6420 for as many as 112 weeks.

Big Pharma has been piling into radiopharmaceuticals, with Novartis the leader in the field thanks to two approved drugs, Pluvicto and Lutathera. But Eli Lilly is closing in, having acquired Point Biopharma for $1.4 billion last year and splashing out $60 million earlier this week to work with Aktis Oncology on therapeutic and diagnostic products against multiple targets.

AstraZeneca also got in on the game in March, buying Fusion Pharmaceuticals for $2 billion and Bristol Myers Squibb picked up RayzeBio for $4.1 billion in December 2023.