In early-stage trials called dose escalation studies, drug developers usually want to test progressively higher doses of their therapies.
Not Perspective Therapeutics. The radiopharma biotech announced Friday morning that it is planning to explore an even lower dose of its radioactive lead-based drug after Phase 1/2a results in 10 melanoma patients showed that those who got the low dose did better than those who got the high one.
The company said there were no dose-limiting toxicities or adverse safety events that led to drug discontinuation, which are typical reasons for companies to test lower doses in early-stage studies.
Perspective is studying an experimental treatment called [²¹²Pb]VMT01, which uses radioactive lead and is targeted at a receptor overexpressed in melanoma called MC1R.
The first cohort of the trial included three patients who received 3.0 millicurie doses of Perspective’s therapy, while the second cohort had seven patients who received 5.0 millicurie doses of the drug. Patients in each cohort received a median of five prior lines of systemic therapy, Perspective said, meaning the patients had already tried a lot of treatments.
In the cohort that got the low dose, one patient had a partial response, and the treatment staved off cancer progression for 13 months. All three patients completed all three cycles of therapy, which were given eight weeks apart. The two other patients in that cohort had stable disease at nine and 11 months from the start of treatment.
Meanwhile, in the high-dose cohort, three patients progressed after the first cycle of treatment, while four progressed after the second cycle. Perspective CEO Thijs Spoor told Endpoints News that those patients saw progression-free survival times that “seemed to track the disease, without any major change that we could see either up or down.” Typically for these patients, the median PFS ranges from two to four months.
Perspective’s shares $CATX fell about 12% on Friday morning.
The company is part of a wave of biotech companies that is testing radiopharma assets that use so-called alpha emitters, one of which is the highly sought-after isotope actinium.
Perspective now plans to test its lead-based radiopharma drug at 1.5 millicurie doses alone and in combination with Bristol Myers Squibb’s checkpoint inhibitor Opdivo. By combining the radiopharma drug with the checkpoint inhibitor, the idea is that the radiopharma drug could stimulate an immune response.
Frances JohnsonChief innovation officer Frances Johnson said that a key goal with radiation-based treatments is “to see if you can get the effect you want with as little radiation as possible,” which also explains why the safety monitoring committee recommended studying a lower dose. The company may also move to test even lower doses.
“There’s a sweet spot here,” Spoor said. “And these patients’ immune systems are so compromised. So trying to push up for monotherapy at a higher dose in patients where there’s so much going on already doesn’t seem to make as much sense, especially given the animal data when we get such extraordinary responses in combination at lower doses.”
In the study, there were four cases of grade 3 adverse events that were deemed unrelated to treatment.