An experimental prostate cancer drug developed by Johnson & Johnson that uses a rare radioactive particle called actinium-225 led to three patients seeing their tumors shrink substantially, but four patient deaths, according to the first results from an early-stage study.
The therapy resulted in five cases of interstitial lung disease, which is inflammation and scarring in the lung, and two of those cases were fatal. The two additional patient deaths were also considered related to treatment — one patient had respiratory failure with Covid-19, and low blood pressure and a decrease in appetite were listed as treatment-emergent adverse events for the other patient.
Nearly 60% of patients in the Johnson & Johnson study also experienced low platelet counts.
The data, which are set to be presented June 3 at the American Society of Clinical Oncology’s annual meeting, will feature 75 patients who received a range of doses of the actinium-based therapy, known as JNJ-6420, in the Phase 1 study.
Mark WildgustThe clinical trial is now running with a cap on cumulative dosing at 500 microcuries of radioactivity, Mark Wildgust, J&J’s VP of global medical affairs, said in an interview with Endpoints News. The two patients who died from interstitial lung disease in the study were treated at cumulative doses above 750 microcuries, Wildgust said, while no patients who received cumulative doses less than 500 microcuries experienced interstitial lung disease.
In the budding radiopharmaceutical field, J&J is one of several companies developing actinium-based therapies, which drugmakers hope will be more potent than currently available radiopharmaceuticals, particularly in prostate cancer.
JNJ-6420 is an antibody for a marker found on prostate cancers called human kallikrein 2 that’s been tagged with actinium-225. The biopharma industry’s interest in using actinium-225 in cancer therapy was piqued by the impressive early results from a 2016 study by German researchers of an actinium-labeled treatment that targeted prostate-specific membrane antigen (PSMA), which is also found on prostate cancer cells.
Novartis, Convergent Therapeutics and Fusion Pharmaceuticals are now running early-stage studies of actinium-based prostate cancer treatments that target PSMA. AstraZeneca announced in March that it was buying Fusion for $2 billion, and Bristol Myers Squibb also acquired the actinium radiopharmaceutical company RayzeBio earlier this year..
In the 36 patients who received 250 microcuries of JNJ-6420, 16 saw their PSA levels fall by at least 50%. PSA, or prostate-specific antigen, is a blood test researchers use to gauge the presence of cancer.
Of those patients, 17 were evaluated at least once after receiving the experimental therapy, and three saw their tumors shrink by at least 30%, according to the results set to be shared at ASCO. One patient went into complete remission.
J&J highlighted the durability of the patient responses — one patient who has been in the study for nearly two years received just three doses of treatment over that time.
By comparison, Novartis’ approved prostate cancer radiopharmaceutical Pluvicto is dosed every six weeks for up to six times.
Wildgust said that Johnson & Johnson is moving forward with an adaptive dosing approach in which a patient is given another dose of JNJ-6420 only when their PSA levels rise rather than on a fixed schedule.
With that approach, the treatment is more tolerable with fewer severe side effects, according to Wildgust.
“Maybe you wait six months, maybe you wait nine months, maybe you wait a year — and then we see PSA rise, and we’ll be able to give another dose,” he said.