CLR 131 Significantly Extends Survival of Heavily Treated Multiple Myeloma Patients in Phase 1 Trial

Heavily treated multiple myeloma patients included in the first four dosing groups of Cellectar Biosciences’ Phase 1 trial lived for a median of 22 months after receiving a single dose of CLR 131, a new trial update shows.

While all patients in the study received CLR 131, impairing a direct comparison of it with other therapies, recent studies report a median overall survival of only nine to 12 months in similar patient populations receiving approved medicines.

“The median overall survival of 22 months in this heavily pretreated patient population is very encouraging. These are patients with limited therapeutic options and, unfortunately, face poor prognoses,” James Caruso, president and chief executive officer of Cellectar Biosciences, said in a press release.

CLR 131 is a phospholipid drug conjugate (PDC) being developed for the treatment of several blood cancers, pediatric cancers, and head and neck cancers. The drug delivers a radioactive, toxic compound directly to cancer cells by targeting specific lipid molecules in their membrane.

Cellectar is testing CLR 131 in multiple myeloma patients in an ongoing Phase 1 clinical trial (NCT02278315). All patients in the trial are heavily treated — having received a median of five prior therapies — and either failed to respond (refractory) or progressed after first responding (relapsed) to proteasome inhibitors and immunomodulatory medicines. In two-thirds of cases, patients were refractory to both treatment types.

Participants in the first four groups received ascending doses of CLR 131 — 12.5 mCi/m², 18.75 mCi/m², 25 mCi/m², or 31.25 mCi/m² — to determine the treatment’s safety and the best dose for further testing.

Initial results had shown that patients in group 1 lived for a median of 26.2 months, while those in groups 2 and 3 had a median overall survival of 15.4 and 10 months, respectively. Patients in group 4 had the best responses to treatment, with all experiencing either a partial reduction of disease burden or disease stabilization.

The findings, along with studies suggesting that a split dose of CLR 131 might be better at extending survival and reducing tumor burden, led researchers to open a fifth group. Those patients received a similar dose as group 4 (31.25 mCi/m²) but split into two administrations of 15.625 mCi/m² each, given one week apart.

Results presented last August showed that these patients had a higher exposure to the treatment, but reached lower peak concentrations in their blood, which will likely reduce side effects and increase CLR 131’s efficacy.

This approach was also deemed safe and well-tolerated and, in December, Cellectar opened a sixth group, where four patients will receive a 37.5 mCi/m² dose, split into two 18.75 mCi/m² injections.

“The convenience afforded by CLR 131 delivered in only one or two doses as currently administered in our ongoing hematology studies makes it a far less intrusive regimen than other treatments that must be administered at regular dosing intervals,” Caruso said. “We believe extending [the study] with a more patient-friendly dosing regimen provides both a distinctive product profile and the potential to provide beneficial patient outcomes even in later lines of therapy.”

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.

Also, Cellectar is planning two additional Phase 1 studies, one for pediatric solid tumors and lymphoma, and another for head and neck cancers in combination with radiation therapy.