COVID-19 Delta Variant Slows Enrollment in Follicular lymphoma Trial

Enrollment in the phase 2b PARADIGME trial (NCT01796171) of ¹⁷⁷Lu lilotomab satetraxetan (Betalutin) in patients with follicular lymphoma has continued despite the surge of the COVID-19 Delta variant, according to a press release by Nordic Nanovector.¹

By August 3, 2021, trial enrollment stood at 93 participants, up from 83 patients in May of 2021. While enrollment is up, it is lower than expected due to the Delta variant’s impact on the company’s ability to screen patients.

The study has an estimated enrollment of 204 participants and an estimated completion date of September 2026. Primary end points include maximum tolerated dose, tumor response rates, and overall response rates.²

The study has 2 parts and 6 arms. Part A has 5 arms. Arm A is now closed to enrollment. In arm 1 of part A, patients received 10MBq/kg in escalated doses with lilotomab pre-dosing. In arm 2, patients received 15MBq/kg in escalated doses without pre-dosing. In arm 3, patients received 15MBq/kg of the agent with rituximab (Rituxan) pre-dosing. In arm 4, patients received 15MBq/Kg in escalated doses with a higher dose of lilotomab pre-dosing. In arm 5, patients received 20MBq/kg with an intermediate dose of lilotomab pre-dosing regimen. In arm 1 of part B, which is open to enrollment, the study agent will be dosed at different levels.

In order to participate in the study, patients must be 18 years of age or older, have a pre-study WHO performance status of 0 or 1, a life expectancy of 3 months or more, <25% tumor cells in bone marrow biopsy, and measurable disease. Patients with known central nervous system metastases, previous treatment with radioimmunotherapy, or test positive for hepatitis B, are not eligible to participate. 

Data from the phase 1 portion of the study, which were presented during the 2020 American Society of Hematology Annual Meeting, found that the study agent is a good alternative for patients who cannot tolerate other treatments.

In total, 57 patients were included in the follicular lymphoma cohort. Dose-limiting toxicities, which were hematologic in nature, closed arms 2 and 3. Non-hematologic AEs include nausea (15.8), upper respiratory tract infection (10.5%), and urinary tract infections (10.5%).

The overall response rate (ORR) in the follicular lymphoma cohort was 65%, with a complete response (CR) of 30%. Partial responses were seen in 35% of patients with and 18% of patients saw stable disease. In follicular lymphoma patients with 2 or more prior therapies, the ORR was 70% with a CR rate of 32%. The median progression-free survival was 9.1 months.

The study is currently recruiting in Arkansas, California, Florida, Illinois, Kentucky, Louisiana, New York, North Carolina, Oregon, Pennsylvania, and Texas.

_REFERENCES:

_{1.Nordic Nanovector provides update on PARADIGME, its phase 2b pivotal trial with Betalutin® in R/R follicular lymphoma. News release. Nordic Nanovector. August 3, 2021. Accessed August 23, 2021. https://bit.ly/3jgJZ8Z.}

_{2.A Phase I/II study of Betalutin for treatment of relapsed non-Hodgkin lymphoma (LYMRIT-37-01). ClinicalTrials.Gov. Accessed August 23, 2021. https://bit.ly/3sE683O.}