Abstract CT540: A phase 1 trial of cytokine-induced memory-like (CIML) natural killer (NK) cell therapy with IL-15 superagonist in advanced head and neck cancer: Part 1 results
Authors: Hanna Glenn J. , Coleman Kimberly , Birch Grace , Redd Robert A. , Alonso Alejandro , Bednarz Samantha , Daley Heather , Hernandez Rodriguez Diego E. , Shaw Kit L. , Haddad Robert I. , Uppaluri Ravindra , Ritz Jerome , Nikiforow Sarah , Soiffer Robert J. , Romee Rizwan 
Published: June 2022

Abstract
Purpose: Outcomes for patients with recurrent, incurable or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) refractory to platinum and immunotherapy are poor. Cellular therapies are emerging treatments with potential utility in epithelial cancers. This proof-of-concept trial investigates an allogeneic cytokine-induced, memory-like (CIML) NK cell infusion with IL-15 superagonist (sa) after lymphodepleting (LD) chemotherapy in advanced SCCHN.
Patients and methods: This phase 1 single-center trial enrolled patients (pts) with R/M SCCHN regardless of human papillomavirus (HPV) status who had prior platinum and immunotherapy. Pts received LD fludarabine (25 mg/m2) and cyclophosphamide (60 mg/m2/kg) on days -6 to -2 prior to haploidentical CIML NK cell infusion on day 0 (5-10 x 106 viable cells/kg=dose level 0) followed by N-803 (IL-15sa, 15 mcg/kg subcutaneously) starting on day +1 every 21-days for 4-doses. Part 1 treated 3 pts at dose level 0; &lt;2 DLTs triggered an additional 3 pts. Part 2 will treat an additional 6 pts with lead-in ipilimumab (day -7). Primary objective: safety, maximum tolerated dose of CIML NK cells. Secondary objectives: objective response rate, progression-free survival (PFS), overall survival (OS), and phenotypic expansion and function of adoptively transferred NK cells.
Results: From 9/8/20 to 9/7/21, 6 pts enrolled to Part 1. One DLT was observed at dose level 0. Among 6 pts, median age: 59; 5/6 (83%) were men; 5/6 (83%) had oropharyngeal primaries (4 HPV+) with a median 6 prior lines of therapy for R/M disease (range: 4-8). R/M disease sites: lung, bone, skin, liver. 5/6 (83%) had offspring donors. Grade (G) 3-4 hematologic adverse events were common (6/6, 100%). One patient died of G5 febrile neutropenia and infection. Median days hospitalized: 14 (range: 9-37). Mild cytokine release syndrome was observed in 5/6 (83%) (median peak ferritin: 2248, CRP: 168); 3/5 required anti-IL6 therapy; no neurotoxicity was noted. There were no dose adjustments or discontinuation of therapy. One (17%) partial response (PR) was observed lasting 6.5 months; 4 (67%) pts had stable disease (SD), and 1 (17%) had progression. Tumor regression was observed in 3/6 (50%) pts at day +30. At a median follow-up of 9.5 months, median PFS: 3.4 months (95%CI 2.6-6.5); median OS: 4.7 months (95%CI 3.4-11.8). CIML NK cells showed large expansion in the peripheral blood (PB) at day +7 in all pts; mean increase: 66% (6-fold; standard deviation [SD] 10.5), to constitute 80% (SD 12.1) of PB lymphocytes. In pts with tumor regression at day +30 compared to those without, the % of PB NK cells remained high at day +28 (mean: 78 vs. 11%). PB NK cells remained &gt;50% at day +42 in the pt with a PR.
Conclusion: Allogeneic CIML NK cells can induce tumor regression associated with persistent CIML NK cell expansion among advanced SCCHN pts. In Part 1 we demonstrate safety and feasibility with the expected risks of LD conditioning. These findings have important implications for the development of cellular therapies in solid tumors.
Citation Format: Glenn J. Hanna, Kimberly Coleman, Grace Birch, Robert A. Redd, Alejandro Alonso, Samantha Bednarz, Heather Daley, Diego E. Hernandez Rodriguez, Kit L. Shaw, Robert I. Haddad, Ravindra Uppaluri, Jerome Ritz, Sarah Nikiforow, Robert J. Soiffer, Rizwan Romee. A phase 1 trial of cytokine-induced memory-like (CIML) natural killer (NK) cell therapy with IL-15 superagonist in advanced head and neck cancer: Part 1 results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT540.