MC# 19-13 - A Phase I Open-label Study of ASP9801, an Oncolytic Virus, Administered by Intratumoral (IT) Injection in Patients with Advanced/Metastatic Solid Tumors
Disease Type(s): Solid Tumor
Drug Classification(s): Viral Therapy, Immunotherapy
Mechanism of Action
ASP9801 is a genetically engineered oncolytic vaccinia virus to be administered by intratumoral injection that expresses both interleukin 7 (IL-7) and interleukin 12 (IL-12).
In this study, the sponsor and investigators want to learn:
- How much of ASP9801 can be given with an acceptable level of side effects
- About the safety and tolerability of ASP9801
- How much of ASP9801 is absorbed into the blood and how fast it is removed
- If research tests can be used in the future to predict who may benefit from the ASP9801
- How proteins that indicate the status of your disease are affected with use ASP9801
- If ASP9801 prevents or delays tumor growth or shrinks an existing tumor
- Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulation (e.g., Health Insurance Portability and Accountability Authorization for United States sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Subject must have histologically- or cytologically-confirmed diagnosis of advanced or metastatic solid tumor(s).
- Subject has measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. At least 1 lesion must be suitable for IT injection. Lesions for injection must be ≥ 10 mm and ≤ 60 mm in longest diameter.
- Subject has progressed on or is not eligible for available standard therapy.
- Subject is age ≥ 18 years.
- Subject has a predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
- Subject has at least 2 sites of disease suitable for biopsy and is willing and able to undergo required tumor biopsies according to the treating institution’s guidelines at screening and during study treatment.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- A female subject is eligible to participate if she is not pregnant [see Appendix 12.3, Contraception Requirements] and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in OR
- WOCBP who agrees to follow the contraceptive guidance as defined in throughout the treatment period and for at least 180 days after the final study IP administration.
- Female subject must agree not to breastfeed starting at screening, and throughout the study period and 180 days after the final study IP administration.
- Female subject must not donate ova starting at screening, and throughout the study period and for 180 days after the final study IP administration.
- Male subject must agree to remain abstinent or use a condom throughout the study period and for 180 days after the final study IP administration.
- Male subject with female partner(s) of childbearing potential must agree to use contraception as detailed in during the treatment period and for at least 180 days after the final study IP administration.
- Male subject must not donate sperm during the treatment period and for at least 180 days after the final study IP administration.
- Subject must be willing and able to comply with the study requirements including prohibited concomitant medication restrictions.
- Subject agrees not to participate in another interventional study while receiving study IP.
- Subject has the ability to understand and the willingness to sign a written informed consent document.
- Subject has ongoing toxicity ≥ CTCAE grade 2 attributable to prior antineoplastic therapies considered clinically significant in the opinion of the investigator.
- Subject who has had major surgery ≤ 4 weeks of screening.
- Subject is concurrently participating in another interventional study or has received an investigational product ≤ 30 days or 5 half-lives prior to first IP administration.
- Subject with symptomatic or untreated central nervous system metastases or leptomeningeal disease. Subjects with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to screening) and off steroids for at least 2 weeks prior to first IP administration.
- Subject with active or prior autoimmune or inflammatory disorders requiring systemic therapy within past 2 years (including inflammatory skin conditions or severe eczema, inflammatory bowel disease (e.g., colitis or Crohn’s disease), diverticulitis (with the exception of diverticulosis), celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.
- The following are exceptions to this criterion:
- Subject with vitiligo or alopecia
- Subject with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Subject with another malignancy that currently requires treatment.
- Subject with tumors encasing major vascular structures such as the carotid artery, tumors adjacent to vital neurovascular structures or tumors in locations that are at high risk for AEs or otherwise not considered appropriate for IT injection.
- Subject with inadequate organ and marrow functions meeting any of the below criteria:
- Leukocytes < 3000/µL
- Absolute neutrophil count < 1500/µL
- Platelets < 100,000/µL
- Hemoglobin (Hgb) < 9 g/dL
- International normalized ratio (INR) > 1.5 × ULN and/or activated partial thromboplastin time (aPTT) > 1.5 × institutional normal limits, except for patients in Group B (Visceral Lesions) escalation and expansion groups where INR and aPTT must be normal
- TBL > 1.5 × institutional normal limits (subjects with known Gilbert syndrome who are excluded if TBL > 3.0 × institutional normal limits or direct bilirubin 1.5 × institutional normal limits)
- AST and ALT > 3.0 × institutional normal limits. Subjects with tumors in the liver
- AST and ALT > 5 × institutional normal limits
- Albumin < 3.4 g/dL
- Creatinine > 1.5 × institutional normal limits
- Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of first administration of study IP. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, any form of substance abuse or psychiatric illness/social situations that would limit compliance with study visits or requirements or a condition that in the opinion of the investigator could invalidate communication with the investigator.
- Subject is known to be positive for human immunodeficiency virus, hepatitis B surface antigen, hepatitis B core immunoglobulin or immunoglobulin G (IgG) antibody or hepatitis C (IgG or RNA test) indicating acute or chronic infection.
- Subject has a history of moderate to severe ascites, clinically significant and/or rapidly accumulating ascites, bleeding esophageal varices, hepatic encephalopathy or pericardial and/or pleural effusions related to liver insufficiency within 6 months of screening. Mild ascites that does not preclude safe IT injection of ASP9801 is allowed at the discretion of the treating physician.
- Subject has a clinically significant abnormal electrocardiogram (ECG) at screening in the investigator’s opinion.
- Subject has symptomatic cardiovascular disease within the preceding 12 months unless cardiology consultation and clearance has been obtained for study participation, including but not limited to the following: significant coronary artery disease (e.g., requiring angioplasty or stenting), acute myocardial infarction or unstable angina pectoris < 3 months prior to screening, uncontrolled hypertension, clinically significant arrhythmia or congestive heart failure (New York Heart Association grade ≥ 2).
- Subject has medical conditions, per the investigator’s judgment, that predispose the subject to untoward medical risk in the event of volume loading (e.g., intravenous fluid bolus infusion), tachycardia or hypotension during or following treatment with ASP9801.
- Subject has a known or suspected hypersensitivity to ASP9801 or any components of the formulation used, including prior adverse reaction to vaccinia (e.g., as smallpox vaccine).
- Subject has had previous exposure with ASP9801.
- Dallas, TX - Mary Crowley Cancer Research - Medical City