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Phase 2 study to investigate the efficacy and safety of IMC‐001, anti‐PD‐L1 antibody, in patients with relapsed or refractory extranodal NK/T cell lymphoma, nasal type: DISTINKT Study

Year: 2023

Type: article

Abstract: Introduction: IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 to enhance T cell activation and retains Fc effector function to stimulate antibody-dependent cell-mediated cytotoxicity. The preclinical results of IMC-001 are comparable to the data of approved PD-1/PD-L1 targeting drugs. Preliminary clinical data in the literature suggest that certain cancers studied in the IMC-001 program, such as extranodal natural killer (NK)/T cell lymphoma (ENKTL), nasal type, are responsive to PD-L1 inhibition. We present efficacy and safety of the phase 2 study of IMC-001 in patients with relapsed or refractory extranodal NK/T cell lymphoma (R/R ENKTL), nasal type. Methods: Patients with histologically confirmed ENKTL who failed to at least one prior systemic therapy including asparaginase-based regimen were enrolled. Patients received IMC-001 20 mg/kg intravenously every two weeks for up to 2 years until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate (ORR) determined by centralized independent review per the Lugano criteria with LYRIC modification for lymphoma. Tumor assessments were performed every 12 weeks using PET-CT/CT. Safety was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: Between October 2020 and February 2023, 15 patients were enrolled. The median age was 59 years (range 46–79), and 13 patients (87%) were male. All patients had a good ECOG performance status of 0–1. Nine patients (60%) were an extranasal type. The median number of prior systemic therapy was 2 (range 1–4). Ten patients (67%) received radiotherapy. Of the 10 efficacy-evaluable patients, 6 patients had a complete response (CR) and an ORR of 60%. A total 6 patients with CR, most of whom received long-term treatment (the median duration of 39 cycles, range 3–52). Most treatment-emergent adverse events (TEAEs) were grade 1–2, and the common TEAEs were fatigue (20%), rash (20%), hypothyroidism (13%), abdominal pain (13%), headache (13%), pruritus (13%), and covid-19 (13%). Grade 2 infusion-related reactions (IRR), grade 3 uveitis, grade 2 hypothyroidism, and grade 2 fatigue suspected to related to IMC-001 were observed in 1 patient each. No TEAEs or serious TEAEs that resulted in death. No long-term toxicity was observed in 4 patients treated for more than 1 year. Conclusions: PD-L1 blockade with IMC-001 is highly effective in patients with R/R ENKTL failing L-asparaginase containing regimens. IMC-001 has a good safety profile without long-term toxicity. We will present updated data for efficacy and safety. (Clinical Trial Identification: NCT04414163) Keywords: Aggressive T-cell non-Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. J. Oh Employment or leadership position: Employee S. Y. Lee Employment or leadership position: Employee H. T. Kim Employment or leadership position: Chief Executive Officer

Source: Hematological Oncology

DOI: 10.1002/hon.3164_433