A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients With Metastatic Solid Tumors

• Published in: The oncologist (Dayton, Ohio) Vol. 28; no. 4; pp. 364 - e217
• Main Authors: Gatti-Mays, Margaret E, Tschernia, Nicholas P, Strauss, Julius, Madan, Ravi A, Karzai, Fatima H, Bilusic, Marijo, Redman, Jason, Sater, Houssein Abdul, Floudas, Charalampos S, Toney, Nicole J, Donahue, Renee N, Jochems, Caroline, Marté, Jennifer L, Francis, Deneise, McMahon, Sheri, Lamping, Elizabeth, Cordes, Lisa, Schlom, Jeffrey, Gulley, James L
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 06.04.2023
• Subjects: Aspartate; Blood cell count; Cancer; Care and treatment; Clinical Trial Results; Clinical trials; Development and progression; Diagnosis; Dosage and administration; Drug therapy; Humans; Influenza; Interleukin-12 - therapeutic use; Metastasis; Monoclonal antibodies; Neoplasms - drug therapy; Neoplasms - pathology; Neoplasms, Second Primary; Product development; Recombinant Fusion Proteins - therapeutic use; Recombinant proteins; State Medicine; Testing; United States; Maryland; NHS-IL12; malignant mesenchymal tumors; malignant epithelial tumors; immunocytokine
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyac244

Abstract Background NHS-IL12 is a first-in-class, recombinant fusion protein composed of the human monoclonal antibody NHS76 (binds exposed DNA/histones at sites of intratumoral necrosis) fused to 2 IL-12 heterodimers. The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of NHS-IL12 monotherapy given subcutaneously (SC) every 4 weeks was previously reported. The study was expanded to include a high-exposure cohort with NHS-IL12 SC every 2 weeks (q2w). Methods This single-arm, phase I trial evaluated NHS-IL12 12 µg/kg SC q2w or 16.8µg/kg SC q2w in patients with metastatic solid tumors. The primary endpoint was safety. Results Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. There was 1 DLT (Grade 3 aspartate transaminase/alanine transaminase [AST/ALT] elevation). Other grade 3 toxicities included: flu-like symptoms 1/13 (8%), decreased absolute lymphocyte count (ALC) 1/13 (8%), decreased white blood cell count (WBC) 1/13 (8%), but most adverse events reported were low grade and self-limiting grade. Fifty percent of evaluable patients (6/12) experienced stable disease (SD) with 42% (5/12) developing progressive disease (PD) at the first restaging. Conclusion Biweekly NHS-IL12 was well tolerated in this small phase I study. Additional studies incorporating NHS-IL12 with other immunomodulating agents are underway. (ClinicalTrials.gov Identifier: NCT01417546). Results of a previously reported phase I trial showed that monthly NHS-IL12 had an acceptable safety profile. This trial was expanded to include a biweekly high exposure cohort where patients with advanced cancers received NHS-IL12 every 2 weeks. Results are reported here.