Shipped from label (Where the package is shipping from) 8. Contact the courier to arrange for a pick-up, if a standard pick- up time is not established for your site or if this was not done in advance. 9. Attach the courier air bill to the top of the box. The shipment should be sent overnight to: Supply and Logistics Agenus Inc. 3 Forbes Road Lexington, MA 02421 United States Tel: +1 (781) 674-4486 supply&logistics@agenusbio.com 119 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 16.7 HSPPC-96 Intradermal Injection Instructions 120 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 HSPPC-96 Intradermal Injection Instructions The route of administration is intradermal injection. Using a 25 g needle or equivalent, inject into 1 site or into 2 adjacent sites (0.2 mL each) a few centimeters apart. Appropriate sites for vaccination include the anterior deltoid regions, subclavicular region bilaterally, and medial inguinal regions of the upper thighs (please see the figure below). Intradermal injections are administered into the outer layers of the skin. The needle should be inserted at a 10-15 degree angle so that it just punctures the skin’s surface. Insert the needle about 0.3 cm below the epidermis and stop when the needle’s tiup is under the skin. You should feel some resistance as you make the injection and a wheal should form as you complete the injection. If the needle tip moves freely, you have inserted the needle too deeply. At this point, withdraw needle slightly and check again for resistance. The appearance of a wheal indicates that the vaccine has entered the area between the intradermal tissues. If a wheal does not appear, withdraw the needle and repeat the procedure in another site a few centimeters apart. Do not administer HSPPC-96 to areas distal to lymph node basins that have been resected or in areas just distal to a surgical scar. Rotate the injection sites so injections are not repeated at the same site forat 2 consecutive administrations and utilize all potential sites for the patient before repeating injections at a previously used injection site. Syringes with slip-tip detachable needles or luer hubs with greater than 0.1 mL dead space should not be utilized. 121 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 122 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 16.8 INFUSION REACTION TREATMENT GUIDELINES NCI CTCAE Grade Treatment Premedication at subsequent dosing Grade 1 Mild reaction; infusion interruption not indicated; intervention not indicatedIncrease monitoring of vital signs as medically indicated until the subject is deemed medically stable in the opinion of the investigator.None Grade 2 Requires infusion interruption but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for < =24 hrsStop Infusion and monitor symptoms. Additional appropriate medical therapy may include but is not limited to: IV fluids Antihistamines NSAIDS Acetaminophen Narcotics Increase monitoring of vital signs as medically indicated until the subject is deemed medically stable in the opinion of the investigator. If symptoms resolve within one hour of stopping drug infusion, the infusion may be restarted at 50% of the original infusion rate (e.g., from 100 mL/hr to 50 mL/hr). Otherwise dosing will be held until symptoms resolve and the subject should be premedicated for the next scheduled dose. Subjects who develop Grade 2 toxicity despite adequate premedication should be permanently discontinued from further trial treatment administration.Subject may be premedicated 1.5h (± 30 minutes) prior to infusion of pembrolizumab with: Diphenhydramine 50 mg po (or equivalent dose of antihistamine). Acetaminophen 500-1000 mg po (or equivalent dose of antipyretic). 123 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 NCI CTCAE Grade Treatment Premedication at subsequent dosing Grades 3 or 4 Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae (e.g., renal impairment, pulmonary infiltrates) Grade 4: Life-threatening; pressor or ventilatory support indicatedStop Infusion. Additional appropriate medical therapy may include but is not limited to: IV fluids Antihistamines NSAIDS Acetaminophen Narcotics Oxygen Pressors Corticosteroids Epinephrine Increase monitoring of vital signs as medically indicated until the subject is deemed medically stable in the opinion of the investigator. Hospitalization may be indicated.