A Study of an Intratumoral Oncolytic Virus in Patients With Advanced Metastatic Solid Tumors

A Phase 1, Open-label Study of ASP9801, an Oncolytic Virus, Administered by Intratumoral Injection in Patients With Advanced/Metastatic Solid Tumors

Sponsors

Lead Sponsor: Astellas Pharma Global Development, Inc.

Source Astellas Pharma Inc
Brief Summary

The purpose of this study is to assess the safety and tolerability of ASP9801 and to determine the recommended phase 2 dose (RP2D). The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of ASP9801.

Detailed Description

The study consists of two parts: dose escalation and recommended phase 2 dose expansion. Each part of the study will include two separate groups of participants. Group A will include participants who will have cutaneous/subcutaneous tumors injected, and group B will include participants who will have visceral tumors injected. The study will consist of the following periods: screening, initial treatment period (two 28 day cycles), optional extended treatment period (continued 28 day cycles) and a follow up period (safety and survival follow up).

Overall Status Recruiting
Start Date 2019-08-08
Completion Date 2024-10-31
Primary Completion Date 2024-10-31
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Dose Limiting Toxicities (DLT) - dose escalation part Up to 28 days
Safety and tolerability assessed by Adverse Events (AEs) Up to 12 months
Number of participants with laboratory value abnormalities and/or adverse events Up to 12 months
Number of participants with vital sign abnormalities and /or adverse events Up to 12 months
Safety assessed by 12- lead electrocardiograms (ECGs) adverse events Up to 12 months
Secondary Outcome
Measure Time Frame
Percent change from baseline in antitumor activity of ASP9801 Up to 12 months
Objective Response Rate Up to 12 months
ASP9801 viral DNA in blood Up to 12 months
Viral shedding of ASP9801 in saliva Up to 12 months
Viral shedding of ASP9801 in urine Up to 12 months
Viral shedding of ASP9801 in skin (cutaneous/subcutaneous only) Up to 12 months
Enrollment 105
Condition
Intervention

Intervention Type: Biological

Intervention Name: ASP9801

Description: Administered by intratumoral injection

Eligibility

Criteria:

Inclusion Criteria: - 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 intratumoral (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 has a predicted life expectancy ≥ 12 weeks. - 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 and at least 1 of the following conditions applies: - Not a woman of childbearing potential (WOCBP) OR - WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study investigational product (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 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. Exclusion Criteria: - Subject has ongoing toxicity ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2 attributable to prior antineoplastic therapies considered clinically significant. - 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 whichever is shorter, 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 adverse events (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 - Total Bilirubin (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) - Aspartate aminotransferase (AST) and Alanine transaminase (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 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 ribonucleic acid (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. - Subject has a clinically significant abnormal electrocardiogram (ECG) at screening. - 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 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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Astellas Pharma Global Development, Inc.
Overall Contact

Last Name: Astellas Pharma Global Development

Phone: 800-888-7704

Email: [email protected]

Location
Facility: Status:
University of Arizona - Arizona Cancer Center | Tucson, Arizona, 85719, United States Recruiting
The Angeles Clinic and Research Institute | Los Angeles, California, 90025, United States Recruiting
Henry Ford Hospital | Detroit, Michigan, 48202, United States Recruiting
Nebraska Methodist Hospital | Omaha, Nebraska, 68130, United States Recruiting
UNC Healthcare | Chapel Hill, North Carolina, 27514, United States Recruiting
University of Toledo Medical Center | Toledo, Ohio, 43614, United States Withdrawn
University of Pittsburgh Medical Center | Pittsburgh, Pennsylvania, 15260, United States Recruiting
Greenville Health System Cancer Institute | Greenville, South Carolina, 27605, United States Recruiting
Mary Crowley Cancer Research Center | Dallas, Texas, 75251, United States Recruiting
The University of Texas - MD Anderson Cancer Center | Houston, Texas, 77030, United States Recruiting
UVA Cancer Center | Charlottesville, Virginia, 22903, United States Recruiting
Seattle Cancer Care Alliance | Seattle, Washington, 98109, United States Recruiting
Location Countries

United States

Verification Date

2021-05-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Dose Escalation - cutaneous or subcutaneous lesions

Type: Experimental

Description: Participants will receive ASP9801 on days 1 and 15 of 28 day cycles to determine the recommended phase 2 dose. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.

Label: Dose Escalation - visceral lesions

Type: Experimental

Description: Participants will receive ASP9801 on days 1 and 15 of 28 day cycles to determine the recommended phase 2 dose. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.

Label: Dose Expansion - cutaneous or subcutaneous lesions

Type: Experimental

Description: Participants will receive ASP9801 on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.

Label: Dose Expansion - visceral lesions

Type: Experimental

Description: Participants will receive ASP9801 on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.

Patient Data Yes
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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