All three relapsed or refractory multiple myeloma patients in the final group of Cellectar Biosciences‘ Phase 1 trial of CLR 131 benefited from treatment, researchers said. Participants had received more than five previous lines of therapy for their cancer.
CLR 131 is a phospholipid-drug conjugate (PDC) being developed for the treatment of several blood cancers. The drug delivers a radioactive, toxic compound directly to cancer cells by targeting specific lipid molecules in their membrane.
Study participants were included in one of four dose groups, or cohorts, to determine the best and safest dosing regimen of CLR 131. Data from the first group had shown that a single dose of CLR 131 improved the survival of patients who had averaged 5.8 prior lines of treatment. The new findings continue to show that CLR 131 has potential in treating relapsed or refractory myeloma.
The U.S. Food and Drug Administration (FDA) has granted CLR 131 orphan drug designation for the treatment of multiple myeloma.
The Phase 1 trial (NCT02278315) is a dose-escalating study to test the safety and tolerability of CLR 131 in heavily treated multiple myeloma patients. Based on data from the last study group, the highest dose tested in the trial was deemed safe and well tolerated by the trial’s Data Monitoring Committee (DMC).
All of the patients experienced clinically relevant improvements. After 85 days of follow-up, two patients had achieved stable disease, and one had a partial response.
To further evaluate the treatment’s effectiveness, researchers used surrogate biomarkers, such as M protein and free light chain (FLC) levels. These are often elevated in multiple myeloma patients, and partial responses are defined as a reduction of at least 50% of these levels, according to the International Myeloma Working Group (IMWG).
One patient with stable disease had a 44% reduction in M protein levels. Meanwhile, the patient with a partial response had an 82% reduction in FLC levels. This patient had received seven prior lines of treatment, including stem cell transplantation and combo therapies.
“The encouraging data from Cohort 4 including the partial response and the DMC’s determination that the 31.25 mCi/m2 of CLR 131 was safe is impressive in light of the highly advanced disease and heavily pretreated patients within the cohort,” Jim Caruso, president and CEO of Cellectar Biosciences, said in a press release.
But while CLR 131 has shown promising results in this Phase 1 trial, recent preclinical data suggest that dosing patients with two or three doses might be better at improving survival and reducing tumor burden than a single dose. So, Cellectar is planning a fifth group to test multiple CLR 131 doses in this patient population.
“Given the preclinical and clinical data results we’ve seen to date, the company intends to advance the compound into a fifth cohort using a multi-dose regimen,” Caruso said.
CLR 131 also is being tested in combination with dexamethasone in a Phase 2 trial (NCT02952508) for relapsed or refractory multiple myeloma and lymphoma. The drug will be tested as a single 25.0 mCi/m2 dose, but patients may be eligible to receive a second infusion.