Results from the CLOVER-1 phase II trial ( NCT02952508 ),investigating the efficacy of CLR 131 for the treatment of patients with refractory multiple myeloma (MM), showed an overall response rate (ORR) of 40% in triple-class refractory patients that received a total dose of ≥ 60 mCi. 1These patients were refractory to proteasome inhibitors, anti-CD38 antibodies, and immunomodulatory agents. This ORR was seen in 6 of 15 patients, from both Part A of this trial (a dose exploration) and Part B — triple-class refractory patients enrolled between March 2020 and May 2020. CLR 131 was reported to be well tolerated, and the most frequent adverse event was cytopenia. No unexpected adverse events were recorded.
This report follows the results that were announced from the phase I dose-escalation trial ( NCT02278315 ) earlier this year. 2Patients with MM who had been treated with a median of five lines of previous therapies (range, 3−17) were included in this study and achieved an ORR of 34.5%. Over half of the patients included (51%) were quad-refractory or greater. Patients were treated with three doses of CLR 131: < 50 mCi, ~ 50 mCi, or ~ 75 mCi. Hematological toxicities were the most common Grade ≥ 3 events that occurred at the highest dose level. These included thrombocytopenia (65%), neutropenia (41%), leukopenia (30%), anemia (24%), and lymphopenia (35%).
CLR 131 is a small-molecule phospholipid ether–drug conjugate that takes advantage of the uptake of phospholipid ethers by malignant cells, in order to deliver a cytotoxic radioisotope (iodine-131) selectively. CLR 131 received fast-track designation from the U.S. Food and Drug Administration last year, as reported by the Multiple Myeloma Hub here. This was followed by the announcement of an orphan drug designation from the European Commission for CLR 131 in MM. 3CLR 131 is also being investigated in relapsed/refractory diffuse large B-cell lymphoma, Waldenström’s macroglobulinemia, and other selected B-cell malignancies. 1
Watch Sikander Ailawadhi discuss CLR 131 at ASH 2019