Initial data from the phase II CLOVER-1 trial demonstrated an acceptable safety profile for CLR 131 in patients with relapsed/refractory B-cell malignancies, including multiple myeloma, Cellectar Biosciences, Inc., announced in a press release.

In the CLOVER-1 trial, the overall response rate (ORR) in the 20 patients who were evaluated was 30%, with a 75% clinical benefit rate. The median progression-free survival (PFS) was 4.5 months in these patients. These responses are promising in patients where standard therapy has an ORR of 25% in similar patient populations, according to Cellectar Biosciences.

The most common adverse events (AEs) included cytopenias, such as thrombocytopenia, anemia, neutropenia, and decrease white blood cell count. Investigators expected to see hematologic AEs, all of which were manageable and followed a predictable timeline to nadir (median 49 days) and subsequent recovery (median 16 days post nadir). More cytopenias occurred in patients with disease in the bone marrow compared with patients with no detectable disease in the bone marrow. However, all patients recovered from the cytopenias.

“The 30% ORR seen suggests that CLR 131 treatment at the single 25 mCi/m2bolus dose may have activity in these heavily pretreated patients,” James Caruso, president and chief executive officer of Cellectar Biosciences, said in a press release. “We recently presented data at [the 2019 American Society of Hematology Annual Meeting and Exposition] on 19 patients with relapsed, refractory multiple myeloma, which showed improved efficacy and safety with fractionated doses versus the single bolus dose, and patients receiving a fractionated dose of 37.5mCi showed a 50% ORR. As background, recently approved drugs for this indication have demonstrated approximate ORRs of 25% in a similar patient population and up to 29% as a third line treatment. We plan to provide additional data in patients who are receiving higher fractionated doses of CLR 131 in January.”

CLOVER-1 is an open-label, multicenter study evaluating CLR 131 in patients with relapsed/refractory B-cell hematologic cancers across 10 cancer centers in the United States. The cancers being investigated include multiple myeloma, chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), lymphoplasmacytic leukemia (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

The trial was designed to determine a safe and effective dose of CLR 131 to be used in a pivotal study in patients with select hematologic malignancies. Of the 20 patients evaluated in the trial, 10 had relapsed/refractory multiple myeloma and 10 had relapsed/refractory B-cell lymphoma.

Of the 20 patients, 13 were male and 7 female. The median age was 71 years (range, 52-82), and the median number of prior lines of systemic therapy was 6 in the patients with multiple myeloma and 4 in the patients with lymphoma. Additionally, 8 patients had a prior autologous stem cell transplantation.

Investigators aim to enroll up to 80 patients. The primary end point of CLOVER-1 is clinical benefit rate, with secondary end points including ORR, PFS, overall survival, and other markers of efficacy. The study is evaluating a fractioned dose of 37.575mCi/m2of CLR 131 administered in 2 30-minute infusions of 18.75mCi/m2 of CLR 131 on days 1 and 7 (± 1), with the option for a second dose cycle 75 to 180 days after.

To be included in the trial, patients have to have a diagnosis of CLL/SLL, LPL, MZL, MCL, histologically or cytologically confirmed myeloma, or a histologically confirmed DLBCL. Patients had to be at least 18 years of age with a life expectancy ≥6 months and an ECOG performance status ≤2. Their platelet counts had to be ≥100,000/µL and their white blood cells ≥3,000/ µL.

Some exclusion criteria for the CLOVER-1 trial include the presence of ongoing grade ≥2 toxicities, prior external-beam radiotherapy resulting in greater than 20% of total bone marrow receiving >20 Gy, prior total body or hemi-body irradiation, ongoing chronic immunosuppressive therapy, and clinically significant bleeding within 6 months.

CLR 131 is a small molecular radiotherapeutic Phospholipid Drug Conjugate (PDC). The PDC delivers cytotoxic radiation directly to the cancer cells and cancer stem cells. The FDA previouslygranted CLR 131 an Orphan Drug Designation for the treatment of patients with multiple myelomain 2014. In 2018, Orphan Drug Designation and Rare Pediatric Disease Designation was granted to the agent for patients with neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma, and osteosarcoma.

Reference:

Cellectar Announces Data From 20 Patients Receiving a Single 25mCi/M2 Bolus Dose of CLR 131 in the Phase 2 CLOVER-1 Study [press release]. Florham Park, NJ: Cellectar Biosciences, Inc; December 16, 2019. https://bit.ly/35wQaMH. Accessed December 17, 2019.