KIROVAX 003 Date: August 22, 2018- Version 00 7 CONFIDENTIAL Page 1 of 47 Phase I/II Study of Low Dose Cyclophosphamide, Tumor Associated Peptide Antigen -Pulsed Dendritic Cell Therapy and Imiquimod , in patients with Progressive and/or Refractory Solid Malignancies. Protocol Number: KIROVAX-003 Date: August 22, 2018 Version: 007 IND Number: 12612 Sponsor: Kiromic , Inc 7707 Fannin Street, Suite 140 Houston, TX 77054 USA Phone: (832) 968-4888 Fax: (866) 419-6193 Confidentiality Statement This document and the information contained herein or attached hereto (“Confidential Material”) is confidential and proprietary to Kiromic (Polaris). The Confidential Material should only be viewed by those individuals or companies that have been given prior authorization to do so by Kiromic (“Authorized Users”). The Confidential Material should not be made available in any form to any person or company, other than the Authorized User and their respective employees or associates on a need -to-know basis, without the prior written consent from Kiromic. KIROVAX 003 Date: August 22, 2018- Version 00 7 CONFIDENTIAL Page 2 of 47 Kiromic Signature Page Signature of Kiromic Study Chair dd mmm yyyy Scott Dahlbeck, MD, PharmD , Chief Medical Officer Printed Name of Kiromic Study Chair and Title By my signature, I indicate I have reviewed this protocol and find its content to be acceptable. 22 Aug 2018 KIROVAX 003 Date: August 22, 2018- Version 00 7 CONFIDENTIAL Page 3 of 47 Principal Investigator Signature Page Signature of Site Principal Investigator dd mmm yyyy Printed Name of Site Principal Investigator Institution Name: _______________________________________ By my signature, I agree to personally supervise the conduct of this study at my study site and to ensure its conduct is in compliance with the protocol, informed consent, Institutional Review Board (IRB)/Ethics Committee (EC) procedures, the Declaration of Helsinki, ICH Good Clinical Practices Guidelines, and local regulations governing the conduct of clinical studies. KIROVAX 003 Date: August 22, 2018- Version 00 7 CONFIDENTIAL Page 4 of 47 TABLE OF CONTENTS ABSTRACT ................................................................................................................................................... 7 1.0 BACKGROUND AND SIGNI FICANCE ................................................................................................... 8 2.0 HYPOTHESIS AND OBJEC TIVES ........................................................................................................ 15 2.1 Hypothesis ................................................................................................................................... 15 2.2 Primary Objective: Phase I .......................................................................................................... 15 2.3 Secondary Objectives: Phase II ................................................................................................... 15 3.0 STUDY DESIGN ................................................................................................................................. 15 3.1 Study Po pulation ......................................................................................................................... 15 3.1.1 Number and Characteristics of Patients Enrolled .............................................................. 15 3.2 Eligibility Criteria ......................................................................................................................... 16 3.2.1 Inclusion Criteria ................................................................................................................ 16 3.2.2 Exclusion Criteria ............................................................................................................... 17 3.3 Withdrawal Criteria ..................................................................................................................... 18 3.3.1 Reasons for Withdrawal of Patients from Study ................................................................. 18 3.3.2 Follow-up of Withdrawn Patients ........................................................................................... 18 3.4 Patient Replacement ................................................................................................................... 18 3.4.1 Reasons for Replacement .................................................................................................... 18 3.5 Study Schedule ............................................................................................................................ 19 3.5.1 Summ ary of Pre -treatment Evaluations .............................................................................. 19 3.5.2 Sum mary of Treatment Visits and Procedures .................................................................... 19 3.6 Safety Endpoints ......................................................................................................................... 20 3.6.1 Rules Based on Dose Limiting Toxicity .............................................................................. 20 3.6.2 Definition of Adverse Event and Adverse Reaction ............................................................ 20 3.6.3 Causality ............................................................................................................................. 20 3.6.4 Recording of Adverse Events (AE) ...................................................................................... 22 3.6.5 Follow- up of Adverse Events .............................................................................................. 23 3.6.6 Adverse Event Monitoring .................................................................................................. 23 3.6.7 Defin ition of Dose -Limiting Toxicity (DLT) ....................................................................... 23 3.7 Immune Efficacy Endpoint .......................................................................................................... 24 3.7.1 Immune Efficacy (IE) Rules ................................................................................................ 24 3.8 Reasons for Discontinuation of Study ......................................................................................... 25 3.9 Potential Risks and Benefits ........................................................................................................ 25 KIROVAX 003 Date: August 22, 2018- Version 00 7 CONFIDENTIAL Page 5 of 47 3.9.1 Known Toxicities Associated with DC Vaccination ............................................................... 25 4.0 METHODS AND ASSESSME NTS .......................................................................................................