Abstract CD37 is an internalizing transmembrane antigen highly expressed on most B-cell malignancies, and is a promising therapeutic target. Betalutin® is a novel CD37-binding murine IgG1 antibody (HH1) labelled with the beta-emitter lutetium-177, in a ready-to-use formulation currently in Phase 1/2 clinical development. Following the completion of recruitment into Arms 1 & 2 of this phase I/II study, efficacy and safety data from patients (pts) receiving Betalutin are reported. Methods: Patients with relapsed incurable NHL of follicular grade I-IIIA, marginal zone, mantle cell, lymphoplasmacytic and small lymphocytic subtypes and with platelet counts ? 150 x109/l were eligible for inclusion in the study. Pts received rituximab (375 mg/m2) on day 1 and 8 to deplete normal B cells. On day 29 pre-dosing with 50mg HH1 (cold CD37 antibody) was administered before Betalutin injection (Arm 1 and phase 2). In Arm 2 Betalutin was administered without HH1 pre-dosing on day 29. The starting doses for Arm 1 and 2 were 10 MBq/kg and 15 MBq/kg respectively. Response was assessed by FDG PET/CT scans. Results: A total of 18 evaluable pts were enrolled into Arm 1/phase II (n = 15) and Arm 2 (n = 3) with a median age of 68 years and either follicular lymphoma (n = 17), or mantle cell lymphoma (n = 1). The number of prior therapies ranged from 1 to 8. An additional, 3 pts have been enrolled in the phase 2 part of the study, data from these pts will also be presented. The most common toxicities observed were hematologic with all DLTs being reversible and manageable. In Arm 1, at 20 MBq/kg (n = 3), G 3/4 neutropenia and/or thrombocytopenia were observed in all pts. Platelet transfusions were given to 2 pts. At 15 MBq/kg (n = 6), 2 DLTs were observed: one G 3 thrombocytopenia lasting >14 days and one G 4 neutropenia/ thrombocytopenia lasting >7 days. Both DLTs recovered without intervention. In Arm 2 with 15 MBq/kg (n = 2) G4 thrombocytopenia was observed in both pts and one patient also had G4 neutropenia lasting >7 days. This pt was hospitalised due to sepsis. No DLTs have been reported at 10 MBq/kg in either arm. Eleven serious adverse events (SAEs) were reported by 8 pts: Atrial fibrillation (n = 2) was the only SAE occurring in more than one pt (at 15 MBq/kg in Arm 1). No secondary malignancies or other long-term events were observed. The overall tumor response rate observed in 17 evaluable pts was 65%, comprising 4/17 complete responses, 7/17 partial responses, 3/17 stable disease and 3/17 progressive disease. In addition, one pt had a confirmed transformed lymphoma at 3 months. One pt is still in remission 3 years after treatment. Conclusions: Betalutin, a single dose, ready-to-use formulation, has a predictable and manageable safety profile. Most AEs were haematological, all transient and reversible. Promising efficacy and durable responses were observed. Betalutin has the potential to be a novel, safe and effective therapy for B-cell malignancies. Citation Format: Arne Kolstad, Ulf Madsbu, Matthew Beasley, Michael Bayne, Caroline Stokke, Tore Bach-Gansmo, Ayca Muftuler Løndalen, Jon Erik Holtedahl, Mona Elisabeth Revheim, Øyvind Bruland, Jostein Dahle, Laurie Baylor Curtis, Åse Østengen, Simon Turner, Nils Bolstad, Roy H. Larsen, Signe Spetalen, Martin Erlanson, Stine Nygaard Rudå, Harald Holte. Efficacy and safety results of Betalutin® (177Lu-DOTA-HH1) in a phase I/II study of patients with non-hodgkin B-cell lymphoma (NHL). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-252.