Enrollment of patients with relapsed or refractory follicular lymphoma in a phase 2 LYMRIT 37-01 PARADIGME study of third-line Lu lilotomab satetraxetan has increased accrual to 2-5 patients per month.
Enrollment of patients with relapsed or refractory follicular lymphoma (FL) in the phase 2 LYMRIT 37-01 PARADIGME study (NCT01796171) of third-line 177Lu lilotomab satetraxetan (Betalutin) in relapsed non-Hodgkin lymphomas (NHLs) has occurred at a rate of 2 to 5 patients per month, which is a significant increase noted by the developer, Nordic Nanovector ASA, in a press release.1
The company had expected that restrictions due to coronavirus disease 2019 (COVID-19) would be reduced over time and allow study operations to improve. Based on the enrollment rates that the trial is currently showing, Nordic Nanovector believes they could accrue about 7 patients per month by late spring. In total, 73 patients have been enrolled as of February 17, 2021.
LYMRIT 37-01 PARADIGME is a 3-part, 6-arm clinical trial that is investigating the maximum-tolerated dose of 177Lu lilotomab satetraxetan in phase 1 of the study and tumor responses in phase 2a and 2b, as primary end points. The study arms explore 177Lu lilotomab satetraxetan at starting doses of either 10 MBq/kg, 15 MBq/kg, or 20 MBq/kg. The agent is administered bi-weekly with or without pre-dosing of either rituximab (Rituxan) or lilotomab.
Eligible patients for the study are those aged 18 years or older with histologically confirmed follicular grade 1-3A, marginal zone, small lymphocytic, lymphoplasmacytic, or mantle cell lymphoma. WHO performance status must be 0-1 in patients prior to joining the study. Patients are also required to have a life expectancy ≥3 months, <25% tumor cells in bone marrow biopsy, and measurable disease by radiological methods.
Phase 1 data for LYMRIT 37-01 PARADIGME were presented during the 2020 American Society of Hematology (ASH) Annual Meeting. Investigators found that 177Lu lilotomab satetraxetan may be a good alternative treatment approach in relapsed/refractory NHL, especially for patients with comorbidities who cannot tolerate certain other treatments.2
In the FL cohort of 57 patients, dose-limiting toxicities (DLTs) ultimately caused the closure of arms 2 and 3. These DLTs were hematologic in nature. Few DLTs experienced in the remaining treatment arms and overall, 2 regimens were chosen for dose expansion in phase 2a study. The first regimen was lilotomab 40 mg in combination with 177Lu-lilotomab satetraxetan 15 MBq/kg in arm 1 and lilotomab 100 mg/m2 plus 177Lu-lilotomab satetraxetan 20 MBq/kg in arm 4.
More than 2% of patients in the study experienced rug-related treatment-emergent adverse events (AEs), which were mainly hematologic AEs. The AEs that were non-hematologic were most commonly nausea (15.8%), upper respiratory tract infections (10.5%), and urinary tract infections (10.5%).
Serious AEs occurred in 14 patients. The serious AEs observed in the study were thrombocytopenia, atrial fibrillation, lymphoma progression, and sepsis. Notably, no febrile neutropenia was observed. Events of special interest include the development of chronic myelomonocytic leukemia, which was observed in 1 of 2 patients.
Interim efficacy results were also presented during the ASH Annual Meeting. It was shown that at a median follow-up of 24.5 months (range, 0.4-60.7), the ORR in the FL population was 65%, which included complete responses (CRs) in 30%, partial responses in 35%, and stable disease in 18%. Overall response data was evaluated in patients with FL who received 2 prior therapies or more, and the ORR in this subgroup was 70% with CRs in 32%.
In terms of survival, the FL population had a median PFS of 9.1 months (95% CI, 6.0-17.3) in patients with FL.
Based on the safety and efficacy data observed with 177Lu-lilotomab satetraxetan Nordic Nanovector ASA and discussions with the FDA, the trial will be proceeding with a smaller study population of 120 patients total rather than 130 for a future filing.
1. Nordic Nanovector sees significant improvement in patient recruitment rate in PARADIGME, its single-arm phase 2 pivotal trial with Betalutin® in r/r follicular lymphoma. News release. Nordic Nanovector. February 18, 2021. Accessed February 22, 2021.
2. Kolstad A, Illidge T, Bolstad N, et al. Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2020; 4 (17): 4091–4101. doi: 10.1182/bloodadvances.2020002583