Phase Ib/IIa Study of Amulirafusp Alfa (IMM0306) in Combination with Lenalidomide in Patients with Relapsed or Refractory CD20-Positive B-Cell Non-Hodgkin's Lymphoma

Introduction: Amulirafusp alfa (IMM0306) is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα added on the N-terminus of both heavy chains. It exerts potent cancer killing efficacy by activating both macrophages and NK cells via blockade 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 preliminary results from a Phase Ib study of IMM0306 in combination with lenalidomide in patients with R/R CD20-positive B-cell NHL.

Methods: This is an open-label, multicenter phase Ib/IIa study (NCT05771883). In phase Ib dose escalation part followed a standard "3+3" design, assessing 2 dose levels of IMM0306 (1.6 mg/kg, 2.0 mg/kg) intravenously administered once a week with 20 mg lenalidomide orally once a day on Days 1-21 of a 28-day cycle until disease progression or intolerable toxicity. Safety was evaluated per CTCAE version 5.0, tumor assessments performed every 8 weeks by Lugano 2014.

Results: As of Jun 24, 2024, 11 patients (9 follicular lymphoma [FL] and 2 marginal zone lymphoma [MZL]) were enrolled. Median age was 50.3 years old with 8 (72.7%) males. The median number of prior line of therapy was 1. All patients received previous anti-CD20 treatment. Preliminary efficacy was based on investigator's assessment with an overall response rate (ORR) of 90.9% (10/11), with 3 patients achieved complete response (CR) (27.3%, all FL) and 7 achieved partial response (PR) (63.6%, 5 FL, 2 MZL). Two DLTs (grade 4 PLT decreased without bleeding) were observed at 2.0 mg/kg IMM0306 in combination with 20 mg lenalidomide dose level, but none at 1.6 mg/kg IMM0306 in combination with 20 mg lenalidomide dose level. Based on the totality of data, 1.6 mg/kg IMM0306 in combination with 20 mg lenalidomide was selected as recommended Phase II dose (RP2D) for R/R FL and MZL. The most common treatment related adverse events (TRAEs) (≥20%) were WBC decreased (72.7%), lymphocyte decreased (63.6%), ANC decreased (63.6%), anemia (54.5%), bilirubin increased (45.5%), PLT decreased (27.3%), Anti-erythrocyte antibody positive (27.3%) and infusion-related reactions (27.3%). Grade ≥3 TRAEs occurred in 10 patients, including lymphocyte decreased (63.6%), ANC decreased (27.3%), WBC decreased (18.2%), PLT decreased (18.2%), pneumonia (9.1%) and pneumonia mycoplasma (9.1%). One patient experienced treatment related serious adverse event (Grade 4 PLT decreased). No patient experienced TRAEs leading to the study drug discontinuation or death. Two patients had a dose reduction of IMM0306, and 4 patients had dose reductions of lenalidomide due to TRAEs. As of July 5, 2024, the data from the phase IIa part (dose expansion showed promising preliminary efficacy. All 6 response-evaluable R/R FL patients who had failed ≥1 prior systemic therapy achieved 100% ORR (6/6) and 66.7% CR (4/6).

Conclusions: 1.6 mg/kg IMM0306 in combination with 20 mg lenalidomide was well-tolerated and with a promising preliminary anti-tumor activity in patients with R/R FL and MZL. This phase Ib/IIa study is ongoing.