Phase Ib trial of IRX-2 plus durvalumab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

• Published in: Oral oncology Vol. 154; p. 106866
• Main Authors: Park, Robin, Li, Jiannong, Slebos, Robbert J.C., Chaudhary, Ritu, Poole, Maria I., Ferraris, Carina, Farinhas, Joaquim, Hernandez-Prera, Juan, Kirtane, Kedar, Teer, Jamie K., Song, Xiaofei, Hall, MacLean S., Tasoulas, Jason, Amelio, Antonio L., Chung, Christine H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2024
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B7-H1 Antigen - metabolism; Cytokines; Durvalumab; Female; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Head and neck squamous cell carcinoma; Humans; IRX-2; Lymphocytes, Tumor-Infiltrating - immunology; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local - drug therapy; Programmed death ligand-1; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - pathology; Tumor infiltrating lymphocytes; Tumor Microenvironment; Head and neck squamous cell carcinoma; Tumor infiltrating lymphocytes; Programmed death ligand-1; Durvalumab; IRX-2
• ISSN: 1368-8375; 1879-0593; 1879-0593
• DOI: 10.1016/j.oraloncology.2024.106866

•Combined IRX-2 and durvalumab has manageable toxicities.•Combined IRX-2 and durvalumab increased PD-L1 expression and increased number of tumor-infiltrating lymphocytes when pre- and on-treatment tumors were compared.•Durable response was observed in one patient with a variant of unknown significance in ARID1A that was predicted to bind her HLA-I alleles with a higher affinity than the reference peptide. IRX-2 is a multi-cytokine immune-activating agent with anti-tumor activity in non-metastatic head and neck squamous cell carcinoma (HNSCC). Here, we evaluated combined IRX-2 and durvalumab in patients with recurrent and/or metastatic HNSCC. This was a phase Ib trial consisting of dose escalation and expansion. Primary endpoints were safety and biomarkers to assess the immune response in the tumor microenvironment including significant increases in PD-L1 expression and CD8 + tumor infiltrating lymphocytes (TIL) comparing pre- and on-treatment tumor biopsies. Secondary endpoints were objective response rates (ORR) and survival outcomes. Sixteen patients were evaluable for response, and nine patients were evaluable for biomarkers. Thirteen patients (68 %) had exposure to prior anti-PD-1 therapy. No dose-limiting or grade ≥ 3 treatment-related adverse events were observed. On-treatment biopsies showed significantly increased PD-L1 (p = 0.005), CD3+ (p = 0.020), CD4+ (p = 0.022), and CD8 + T cells (p = 0.017) compared to pre-treatment. Median overall survival and progression-free survival (PFS) were 6.18 months (95 % CI, 2.66–8.61) and 2.53 months (95 % CI, 1.81–4.04), respectively. One patient had an objective response (ORR, 5.3 %) with an ongoing PFS of > 25 months. Disease control rate was 42 %. The responder harbored an ARID1A variant of unknown significance (VUS) that was predicted to bind her HLA-I alleles with a higher affinity than the reference peptide. IRX-2 and durvalumab were safe and elicited the evidence of immune activation in the tumor microenvironment determined by increased PD-L1 expression and CD8+ TILs. Clinical Trial Registration Number: NCT03381183.