Introduction: CLR 131 (I-131-CLR1404) is a novel targeted radiotherapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Based on preclinical and clinical experience and the radiosensitivity of MM, CLR 131 is being examined in relapsed or refractory B-cell malignancies through an open-label, phase 2 trial, CLOVER-1 (NCT02952508); initial results in pts with LPL/WM are reported here.

Procedures: The primary objective of this study is to determine the efficacy and safety of CLR 131 in select B-cell malignancies. Eligibility criteria include adult pts with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Wadenstrom's macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or diffuse large B-cell lymphoma (DLBCL). Pts with LPL/WM must have received at least two prior treatment regimens unless ineligible to receive standard agents and have measurable disease: either a nodal lesion > 15 mm, an extranodal lesion > 10 mm, or measurable IgM. Prior external beam radiation therapy is allowed (< 20% of total marrow irradiated). CLR 131 is administered intravenously up to 30 minutes at total body doses (TBD) of <50 mCi, ~50 mCi, and ~75 mCi. Adverse events (AEs) are graded by NCI-CTCAE v4.03; responses are assessed by the 2012 WM Criteria for Response Assessment.

Results: Four pts with LPL/WM have been enrolled in the study with data presented as of 1 Mar 2020. The median age was 70 (range 54-81) and included 2 females and 2 males who had a median of two prior regimens (range 1-5). The overall response rate was 100%, including one pt with a complete response, one pt with a partial response, and one pt with a minimal response; one pt remains under evaluation. The primary treatment-emergent AEs across all doses in pts with LPL/WM included neutropenia, thrombocytopenia, nausea, fatigue, anemia, and decreased white blood cell count, in line with experience to date with CLR 131 in other B-cell malignancies. Median time to resolution of cytopenias was 21 days. One pt received two cycles of CLR 131 with a TBD of ~100 mCi. The pt was determined to be a partial response 43 days post initial dose and a complete response at approximately 200 days; this was confirmed radiologically 406 days post initial dose. The duration of response for this pt is currently at 25 months and is ongoing. One pt received ~ 50 mCi CLR 131 and saw an 89% decrease in IgM at 64 days post infusion. One pt received ~ 75 mCi CLR 131 and had a 45% decrease in IgM at 64 days post infusion. One pt received two cycles of CLR 131 with a TBD of ~150 mCi, experiencing a 48% reduction in IgM to date and has not yet completed the evaluation period.

Conclusions: CLR 131 is a unique, first-in-class targeted radiotherapeutic in development for multiple B-cell hematologic malignancies. The observed positive signals of efficacy and safety from this preliminary data in relapsed or refractory LPL/WM pts is encouraging and will be further explored.

Citation Format: Sikander Ailawadhi, Jarrod Longcor, Kate Oliver, Igor D. Grachev. CLR 131 demonstrates 100% overall response rate in relapsed or refractory lymphoplasmacytic lymphoma (LPL)/Waldenstrom's macroglobulinemia (WM): initial results from ongoing phase 2 trial, CLOVER-1 study [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-25.