Therapy for Heavily Treated Multiple Myeloma Gets Fast Track Status from FDA

Cellectar Biosciences’ candidate CLR 131 received Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma patients who have failed at least four prior lines of therapy, the company announced.

The designation is intended to speed the therapy’s development and review, and enables more frequent communication with the FDA. Treatment candidates with this status may also benefit from accelerated approval and priority review.

“Fast Track Designation furthers our efforts to expeditiously develop CLR 131 as a new, innovative therapy for patients with relapsed/refractory multiple myeloma,” James Caruso, president and CEO of Cellectar, said in a press release. “Patients with third-line or later relapsed/refractory multiple myeloma have a poor prognosis and low rates of survival as a result of limited effective treatment options.”

CLR 131 is a phospholipid drug conjugate (PDC) that delivers a radioactive toxic compound directly to cancer cells by targeting specific lipid molecules in their membrane.

The therapy is being evaluated in Phase 1 (NCT02278315) and Phase 2 (NCT02952508) studies, both recruiting participants.

The Phase 1 trial is including heavily treated patients — those enrolled have so far received a median of five prior therapies — who failed prior treatment with a proteasome inhibitor and an immunomodulatory medicine. In two-thirds of cases, patients were refractory (failed to respond) to both treatment types.

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

Early data has shown that CLR 131 leads to very promising survival outcomes, with patients in groups 1, 2, and 3 living for a median of 26.2, 15.4, and 10 months. However, while survival results are not yet available for group 4, researchers saw the best treatment responses in this group of patients, 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, prompted researchers to open two additional groups: a fifth cohort received the same dose as group 4 (31.25 mCi/m²) but split into two administrations of 15.625 mCi/m² each, given one week apart; and a sixth group where patients are given a 37.5 mCi/m² dose, split into two 18.75 mCi/m² injections.

Initial results from cohort six showed that the 37.5mCi/m² fractionated dose was safe and well- tolerated, with half of patients experiencing a partial response, and the other half a minimal response. Overall, all patients benefitted from the treatment, researchers said.

Moreover, compared to prior groups, patients in cohort 6 showed a 50% partial response rate, a 50% minimal response rate and in all of them the cancer either decreased or remained stable.

The company has since opened a seventh cohort to assess the potential benefits of a 40mCi/m² fractionated dose of CLR 131. Data from this cohort is expected by year’s end.

“We are observing a clear dose response with greater and more prolonged median reductions in surrogate efficacy markers throughout the study safety evaluation period as compared to prior cohorts, along with an improved overall drug profile with our fractionated dosing regimen,” Caruso said in another press release.

“The Data Monitoring Committee unanimously agreed the study should progress to a Cohort 7 with a higher 40 mCi/m² fractionated dose. This cohort has been initiated with data expected in [the fourth quarter of] 2019,” he said.

CLR 131 also is being tested in combination with dexamethasone in relapsed or refractory multiple myeloma and lymphoma patients in the CLOVER-1 Phase 2 trial. The therapy will be given as a single 25.0 mCi/m² dose, but patients may be eligible to receive a second infusion.

Top-line results from the first 10 myeloma patients have shown a 30% overall response rate after a single 30-minute infusion of CLR 131. These patients had been treated with an average of five lines of systemic therapies prior to receiving CLR 131.

One patient showed a very good partial response — a 90% or greater reduction in a disease marker — and two other patients had partial responses, as shown by a decrease of 50% to 89% in the disease marker. The remaining had stable disease.

“Based on data in the initial patient cohort from our ongoing CLOVER-1 trial where patients showed a 30% response rate after receiving a single 25.0 mCi/m² dose as a seventh line of therapy on average, we are optimistic that CLR 131 has the potential to provide a meaningful treatment option for these patients,” Caruso said.