Rituximab Added to 177-Lu Lilotomab Satetraxetan Induces High Response Rate in R/R FL

Preliminary data from a phase 1b trial show a small cohort of patients with follicular lymphoma (FL) who are treated with lutetium (177-Lu) lilotomab satetraxetan (Betalutin) plus rituximab (Rituxan) in the second-line setting demonstrated a high rate of complete responses, according to the company responsible for developing the radioimmunotherapy, Nordic Nanovector ASA.¹

In the ongoing, open-label, single-arm, multi-center, dose-escalation Archer-1 trial (NCT03806179), all 7 evaluable patients achieved at least a partial response to therapy including 5 complete responses. All responses remain ongoing, 5 of which have lasted at least 2 years since administration of 177-Lu lilotomab satetraxetan.

The primary end point of the trial is to evaluate the safety and tolerability of the combination per CTCAE version 4.03 with a secondary end point of preliminary antitumor activity per Cheson 2014. The starting doses included 40 mg of lilotomab and 10 MBq/kg of 177-Lu lilotomab satetraxetan which was escalated to 10 MBq/kg in the second cohort. Patients were treated with weekly rituximab at 375 mg/m2on days 7, 14, 21, and 28 and those who did not progress received the anti-CD20 agent as maintenance for up to 2 years.

To be eligible for the trial, patients must have an ECOG performance status of 2 or less, histologically confirmed diagnosis of FL, at least 1 but not more than 3 prior regimens, at least 1 measurable lesion by CT/MRI, normal organ and bone marrow function, and a life expectancy of at least 3 months.

“We are encouraged by the results in this small phase 1 study in second-line FL patients. Both the overall safety of this combination and the preliminary signs of efficacy are promising,” Peter Braun, Nordic Nanovector CEO, said in a press release. “We look at this study as an additional building block in our overall strategy to develop Betalutin for difficult to treat hematological tumors. Our near-term focus remains very much on completing PARADIGME in [third-line] FL and delivering top line 3-month data by the end of 2021.”

Prior data from a phase 1/2 study (NCT01796171) of 177-Lu lilotomab satetraxetan with or without pre-dose lilotomab in patients with relapsed non-Hodgkin lymphoma, including FL, were published in Blood Advances in September 2020.² For patients with FL who received 2 or more lines of prior therapy (n = 37), the overall response rate was 70% including 32% complete responses. For patients with FL who had previously received rituximab with 2 or more prior lines (n = 21), those rates were 67% and 24%, respectively. Prior to 177-Lu lilotomab satetraxetan administration, patients were pretreated with rituximab and lilotomab to improve tumor targeting.

In 74 patients with relapsed/refractory indolent non-Hodgkin lymphoma, the most common adverse events (AE) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%), with grade 1/2 nausea (15.8%) as the most frequent nonhematologic AE.

177-Lu lilotomab satetraxetan is a next-generation single-dose CD37-directed agent, consisting of lilotomab, a monoclonal antibody with activity against CD37, and the chelator satetraxetan which conjugates the β-emitting isotope 177Lu.

References

1. Nordic Nanovector Announces Update from Archer-1 Phase 1b Trial of Betalutin® in combination with rituximab in 2L Follicular Lymphoma. News release. Nordic Nanovector. May 25, 2021. Accessed May 25, 2021. https://bit.ly/3fh9YuO

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