177 Lu-Lilotomab Satetraxetan, a Novel CD37-Targeted Antibody-Radionuclide Conjugate in Relapsed Non-Hodgkin's Lymphoma (NHL): Updated Results of an Ongoing Phase I/II Study (LYMRIT 37-01)
The incidence of indolent NHL (iNHL) is increasing, with approximately 63,000 new cases per year in the US. The highest unmet medical need is for rituximab (RTX)-refractory patients (pts), with inferior 5 year overall survival rates for RTX-refractory follicular lymphoma (FL) vs all FL pts (58% vs 8...
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| Published in: | Blood 2017-12, Vol.130, p.2769-2769 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
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| Summary: | The incidence of indolent NHL (iNHL) is increasing, with approximately 63,000 new cases per year in the US. The highest unmet medical need is for rituximab (RTX)-refractory patients (pts), with inferior 5 year overall survival rates for RTX-refractory follicular lymphoma (FL) vs all FL pts (58% vs 87.7%) (Abdollahi S et al. Blood 2008; www.seer.cancer.gov). Many pts develop resistance to RTX or RTX-containing regimens, thus targets other than CD20 are important. CD37 is highly expressed (>90%) in most B-cell NHL, providing an alternative target to CD20. Lutetium (177Lu) lilotomab satetraxetan (Betalutin®) is a novel beta-emitting anti-CD37 antibody radionuclide conjugate (ARC) in a ready-to-use formulation that is being evaluated in a phase I/II, open-label, dose-escalation study (LYMRIT 37-01) to determine the safety and preliminary efficacy of Betalutin® monotherapy in pts with relapsed/refractory NHL, and establish a recommended phase II dose (RP2D). Lilotomab (cold antibody) pre-dosing was determined to be essential to optimize Betalutin® biodistribution and safety, and dosimetry data indicate less bone marrow (bm) uptake of Betalutin® with lilotomab pre-dosing with no impact on tumor absorbed dose (Blakkisrud et al. J Nucl Med 2017). Arms 1 and 4 are evaluating 2 different lilotomab pre-doses (Arm 1 - 40 mg; Arm 4 -100mg/m2) with escalating doses of Betalutin®. We provide here an update on safety/efficacy for the 2 arms.
Methods: Pts with histologically confirmed iNHL (FL grade I-IIIA, mantle cell (MCL), marginal zone (MZL), SLL) with ≥1 prior therapies, 150 x 109/L, no prior SCT/RIT, and a life expectancy of ≥3 months were enrolled into 1 of 4 dose-escalation arms (part 1) to determine the optimal lilotomab pre-dose and Betalutin® regimen for further evaluation in an expanded phase II cohort (part 2). All pts received pre-treatment with RTX. Responses were assessed using Cheson IWG response criteria (including CT and PET-CT scans) beginning at week 12.
Results: As of 3 July 2017, 61 pts have been enrolled at 12 centers (55 pts are evaluable for safety having completed 12 weeks of follow-up;55 pts for efficacy). NHL subtypes were FL (n=40; 73%), MCL (n=7; 13%), and MZL (n=8; 14%). Median age was 69; 39 (71%) were ≥ 65. The median no. of prior therapies was 3 (range 1-8); 40 pts (73%) received ≥2 prior therapies, and 31 pts (56%) received ≥2 prior RTX courses. The most common grade (G) 3/4 AEs were hematologic (neu |
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| ISSN: | 0006-4971 1528-0020 |