Phase II safety and preliminary efficacy of amulirafusp alfa (IMM0306) in combination with lenalidomide in patients with relapsed or refractory CD20-positive follicular lymphoma.

7051 Background: Amulirafusp alfa (IMM0306) consists of anti-CD20 monoclonal antibody fused with the CD47 binding domain of SIRPα. It exerts potent anti-cancer efficacy by activating both macrophages and NK cells via blockading of CD47-SIRPα interaction and FcɣR engagement. Lenalidomide was approved for relapsed or refractory (R/R) indolent non-Hodgkin's lymphoma (iNHL). Here, we report results from a Phase II study of 34 patients with R/R CD20-positive follicular lymphoma (FL) (NCT05771883). Methods: Eligible patients with grade 1-3a FL received amulirafusp alfa 1.6 mg/kg intravenously once a week with lenalidomide 20 mg orally once a day on Days 1 to 21 in each 28-day cycle until disease progression or intolerable toxicity. Safety was evaluated by CTCAE 5.0, tumor assessments performed every 8 weeks by Lugano 2014. Results: Until Dec 26, 2024, 34 patients with R/R FL were enrolled. Median age was 54, 20 (58.8%) were males, and 32 (94.1%) had stage III-IV disease. The median number of prior line therapy was 2. All patients received previous anti-CD20 therapy. Among 22 efficacy-evaluable patients, 10 CR, 8 PR, 2 SD and 2 PD were observed. The CRR and ORR were 45.5% and 81.8%, respectively. Of the 4 efficacy-evaluable patients who did not achieve response, 2 SD patients were both CD20 therapy refractory, 1 PD patient had histologic transformation and 1 PD patient were lenalidomide-resistant (had taken lenalidomide continuously for about 4 years). The most common treatment related adverse events (TRAEs) (≥ 20%) were PLT decreased (70.6%), WBC decreased (58.8%), anemia (52.9%), ANC decreased (52.9%), lymphocyte decreased (52.9%), infusion-related reactions (35.3%) and hypoalbuminaemia (23.5%). Grade ≥3 TRAEs occurred in 22 (64.7%) patients, the most common ≥ grade 3 TRAEs (≥ 10%) were ANC decreased (29.4%), lymphocyte decreased (26.5%), PLT decreased (23.5%) and WBC decreased (11.8%). 5 (14.7%) patients experienced serious TRAE. 1 (2.9%) patient had a dose reduction of amulirafusp alfa, 5 (14.7%) patients had dose reductions of lenalidomide due to TRAEs. 1 (2.9%) patient experienced TRAE leading to the study drug discontinuation (Grade 4 Type I hypersensitivity, recovered with sequelae within 1 month). No patient experienced TRAE leading to death. There were no significant differences between amulirafusp alfa monotherapy and combination with lenalidomide in terms of PK exposure and ADA incidence rate. Pharmacodynamics analysis demonstrated amulirafusp alfa combine lenalidomide effectively depleted CD19 + B cell in peripheral blood and achieved sustained long-term B cell depletion. Conclusions: Amulirafusp alfa in combination with lenalidomide showed a preliminary anti-tumor activity and a well-tolerated safety profile in patients with R/R FL. This phase Ib/Ⅱ study is still ongoing. Clinical trial information: NCT05771883 .