Early Data on Lead-Based Radiopharma Asset Shows Lower Dose Performed Better

In early-stage clinical trials known as dose escalation studies, drug developers usually test increasingly higher doses of their therapies. However, Perspective Therapeutics is taking a different approach. The radiopharmaceutical biotech firm announced plans to investigate a lower dose of its radioactive lead-based drug after Phase 1/2a trial results in 10 melanoma patients revealed that those who received the lower dose showed better outcomes than those on the higher dose.

The company reported no dose-limiting toxicities or adverse safety events that led to discontinuation, which are common reasons for companies to test lower doses in early-stage studies.

Perspective is developing an experimental treatment called [²¹²Pb]VMT01, which employs radioactive lead and targets a receptor overexpressed in melanoma, MC1R. The initial trial cohort included three patients who received 3.0 millicurie doses of the therapy, while a second cohort of seven patients received 5.0 millicurie doses. Each patient had undergone a median of five prior lines of systemic therapy, indicating they had already tried multiple treatments.

In the low-dose cohort, one patient experienced a partial response, and the treatment halted cancer progression for 13 months. All three patients in this group completed all three therapy cycles, administered eight weeks apart. The other two patients had stable disease at nine and 11 months, respectively, from the start of the treatment.

Conversely, in the high-dose cohort, three patients showed disease progression after the first treatment cycle, and four more progressed after the second cycle. Perspective’s CEO, Thijs Spoor, noted that the progression-free survival (PFS) times in these patients "seemed to track the disease" with no significant changes observed. Typically, the median PFS for such patients ranges from two to four months.

Following the trial results, Perspective’s shares fell by approximately 12%. The company is among a group of biotech firms exploring radiopharmaceutical assets that utilize alpha emitters, including the highly coveted isotope actinium.

Perspective now intends to test its lead-based radiopharmaceutical drug at 1.5 millicurie doses, both alone and in conjunction with Bristol Myers Squibb’s checkpoint inhibitor, Opdivo. The rationale behind combining the radiopharma drug with the checkpoint inhibitor is to potentially stimulate an immune response.

Frances Johnson, the Chief Innovation Officer, explained that a primary objective with radiation-based treatments is "to see if you can get the effect you want with as little radiation as possible." This goal is consistent with the safety monitoring committee's recommendation to study a lower dose. The company may also consider testing even lower doses in the future.

“There’s a sweet spot here,” Spoor mentioned. “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 instances of grade 3 adverse events, though they were deemed unrelated to the treatment.