See Manual of Preparation of approved ancillary supplies. 14.2.5 Administration Pr ocedures See S ection 3.2. 14.2.6 Incompatibilities Not available. 14.3 NHS -IL12 (IND # 019267) 14.3.1 Source / Acquisition and Accountability NHS -IL12 is manufactured and supplied by EMD Serono. NHS -IL12 will be provided to the clinical trial site by the manufacturer. The investigator or designee (e.g., pharmacist) will maintain an ongoing inventory of the investigational product supply according to standard site procedures. The investigational product will be dispensed at the direction of an investigator for administration to a study participant enrolled on the clinical trial. Disposal of expired or unused product will be returned to the manufacturer or disposed of according to standard site procedures based on agreement between the manufacturer and the site. 14.3.2 Toxicity Subjects (n=59) were treated subcutaneously with NHS -IL12 in a single ascending dose cohort followed by a multiple ascending dose cohort (n=37 with every 4 -week dosing). The primary objective of this trial was to determine MTD as defined by the number of DLTs. None of the subjects treated with single or multiple doses up to 12.0 µg/kg experienced a DLT. At 16.8 µg/kg, 1/6 subjects had a DLT (grade 3 increase in alanine transaminase [ALT]). At 21.8 µg/kg, 2/6 subjects had a DLT (grade 3 increase in aspartate transaminase [AST] and ALT; grade 3 increase in lipase without clinical signs of pancreatitis). MTD was 16.8 µg/kg. The most frequently observed treatment -related adverse event (TRAE) was decreased lymphocyte count (27/59 subjects; 45.8%). Other TRAEs included decreased white blood cells (WBCs) (24/59; 40.7%), fever and elevated AST (21 each; 35.6%), elevated ALT (20; 3.9%), and anemia and flu- like symptoms (18 each; 30.5%) (Table 2; Supplemental Figure 5). Among the cohort receiving 16.8 µg/kg, the most f requently reported TRAEs were elevated AST (75%), decreased WBCs and elevated ALT (68.8% each), and decreased lymphocyte count and fever (62.5% each). At least one grade ≥ 3 TRAE was seen in 12/59 subjects (20.3%). These included decreased lymphocyte count (5; 8.5%), decreased neutrophil count (4; 6.8%), elevated ALT (3; 5.1%), decreased WBCs (2; 3.4%), and hypokalemia, hyperhidrosis, elevated alkaline phosphatase, AST, and lipase (1 each; 1.7%). All grade ≥ 3 TRAEs were transient; only hyperhidrosis was symptomatic. One grade 4 TRAE was observed (asymptomatic decreased lymphocyte count); no grade 5 TRAE was observed. 14.3.3 Formulation and P rep aration NHS -IL12 is formulated as a 1.5 mg/mL solution and is supplied by the Sponsor in single -use glass vials with a rubber stopper and sealed with an aluminum Flip Off® crimp seal closure. 90 Abbreviated Title: Combo Immunotx in HPV Cancers Version Date: 05.12.2023 The contents of the NHS -IL12 vials are sterile and nonpyrogenic, and do not contain bacteriostatic preservatives. Any spills that occur should be cleaned up using the facility’s standard cleanup procedures for biologic products.