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Clinical Trial
. 2020 Sep 8;4(17):4091-4101.
doi: 10.1182/bloodadvances.2020002583.

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Arne Kolstad  1 , Tim Illidge  2 , Nils Bolstad  3 , Signe Spetalen  4 , Ulf Madsbu  5 , Caroline Stokke  6 , Johan Blakkisrud  6 , Ayca Løndalen  7 , Noelle O'Rourke  8 , Matthew Beasley  9 , Wojciech Jurczak  10 , Unn-Merete Fagerli  11 , Michal Kaščák  12 , Mike Bayne  13 , Aleš Obr  14 , Jostein Dahle  15 , Lisa Rojkjaer  15 , Veronique Pascal  15 , Harald Holte  1
Affiliations
Clinical Trial

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Arne Kolstad et al. Blood Adv. .

Abstract

For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

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Conflict of interest statement

Conflict-of-interest disclosure: A.K. declares advisory board participation for Nordic Nanovector ASA. T.I. declares advisory board participation for Nordic Nanovector ASA, Roche, and Takeda. S.S. declares lecture honoraria from Novartis and Sanofi Genzyme. W.J. declares research funding/grants from Nordic Nanovector ASA. U.-M.F. declares advisory board participation for Takeda and Roche. H.H. declares advisory board participation for Nordic Nanovector ASA, Novartis, Roche, Gilead, and Takeda and lecture honoraria from Novartis. J.D. and V.P. are employees of Nordic Nanovector ASA and owners of performance share units. J.D. also declares ownership of shares. L.R. was an employee of Nordic Nanovector ASA at the time of this study. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Dose-escalation and expansion cohorts. Shaded doses selected for dose expansion. D, day.
Figure 2.
Figure 2.
SPECT, dosimetry, and PK comparison by study arm.
Figure 3.
Figure 3.
Effect of different phase 1 regimens on mean neutrophil and platelet counts. Horizontal dotted lines show cut-offs for grade 3 and 4 neutropenia (A) and thrombocytopenia (B).
Figure 4.
Figure 4.
Best percentage change in tumor size from baseline for evaluable patients in phases 1 and 2a.
Figure 5.
Figure 5.
Duration of response and progression-free survival. (A) Kaplan-Meier estimate of DoR. (B) Kaplan-Meier estimate of PFS.
See this image and copyright information in PMC

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