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 as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced/Metastatic Solid Tumors
3 other identifiers
interventional
72
1 country
17
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 as a single agent, as well as in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) checkpoint inhibitor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2019
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 14, 2019
CompletedFirst Posted
Study publicly available on registry
May 17, 2019
CompletedStudy Start
First participant enrolled
September 3, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 19, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 19, 2024
CompletedApril 22, 2025
April 1, 2025
4.6 years
May 14, 2019
April 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Dose Limiting Toxicities (DLT) - dose escalation part
Incidence of dose limiting toxicities
Up to 28 days
Safety and tolerability assessed by Adverse Events (AEs)
An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP.
Up to 12 months
Number of participants with laboratory value abnormalities and/or adverse events
Number of participants with potentially clinically significant laboratory values.
Up to 12 months
Number of participants with vital sign abnormalities and /or adverse events
Number of participants with potentially clinically significant vital sign values.
Up to 12 months
Safety assessed by 12- lead electrocardiograms (ECGs) adverse events
12-lead ECGs will be read and assessed locally. Any clinically significant adverse changes on the ECG will be reported as Adverse Events.
Up to 12 months
Secondary Outcomes (8)
Percent change from baseline in antitumor activity of ASP9801
Up to 12 months
Objective Response Rate per imRECIST
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
- +3 more secondary outcomes
Study Arms (8)
Dose Escalation - cutaneous or subcutaneous lesions
EXPERIMENTALParticipants will receive ASP9801 (1x10\^7 pfu/mL) 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.
Dose Escalation - visceral lesions
EXPERIMENTALParticipants will receive ASP9801 (1x10\^8 pfu/mL) 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.
Dose Expansion (Monotherapy) - cutaneous or subcutaneous lesions
EXPERIMENTALParticipants will receive ASP9801 (1x10\^8 pfu/mL) 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.
Dose Expansion (Monotherapy) - visceral lesions
EXPERIMENTALParticipants will receive ASP9801 (5x10\^8 pfu/mL) 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.
Dose Expansion (Monotherapy Induction) - cutaneous or subcutaneous lesions
EXPERIMENTALParticipants will receive ASP9801 (5x10\^8 pfu/mL) on days 1, 8, 15 and 22 of the first 28 day cycle. Participants will receive ASP9801 on days 1 and 15 on the second 28 day cycle 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.
Dose Expansion (Combination Therapy) - cutaneous or subcutaneous lesions
EXPERIMENTALParticipants will receive ASP9801 (1x10\^8 pfu/mL) on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. Participants will also receive pembrolizumab starting on day 1 and once every 6 weeks. 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.
Dose Expansion (Combination Induction Therapy) - cutaneous or subcutaneous lesions
EXPERIMENTALParticipants will receive ASP9801 (5x10\^8 pfu/mL) on days 1, 8, 15 and 22 of first 28 day cycle at the dose recommended by the dose escalation phase. Participants will also receive pembrolizumab starting on day 1 and once every 6 weeks. Participants will receive ASP9801 on days 1 and 15 on the second 28 day cycle 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.
Dose Expansion (Combination Therapy) - visceral lesions
EXPERIMENTALParticipants will receive ASP9801 (5x10\^8 pfu/mL) on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. Participants will also receive pembrolizumab starting on day 1 and once every 6 weeks. 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.
Interventions
Administered by intratumoral injection
Administered by Intravenous Infusion
Eligibility Criteria
You may qualify if:
- 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 had disease progression after, been intolerant to, or has refused all available therapies that are known to confer clinical benefit. Note: There is no limit to the number of prior treatment regimens.
- 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 as documented by negative pregnancy test within 72 hours prior to treatment 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.
- +2 more criteria
You may not qualify if:
- Subject has ongoing toxicity ≥ National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) grade 2 attributable to prior antineoplastic therapies considered clinically significant.
- Subject who has had major surgery ≤ 4 weeks of screening. Subjects must have recovered from prior procedures and/or any complications from surgery prior to starting study treatment.
- 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 (CNS) metastases or leptomeningeal disease. Subjects with treated symptomatic brain metastases should be neurologically stable (without evidence of progression by imaging for at least 4 weeks prior to screening and any neurologic symptoms have returned to baseline) and off steroids for at least 2 weeks prior to first IP administration. Subjects with carcinomatous meningitis are excluded regardless of clinical stability.
- 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 only 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. Subjects with such tumors that have other injectable tumors would be eligible.
- 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
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Astellas Pharma Global Development, Inc.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (17)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
University of Arizona - Arizona Cancer Center
Tucson, Arizona, 85719, United States
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
The University of Chicago Medical Center
Chicago, Illinois, 60637, United States
University of Kentucky, Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Cancer Institute
Louisville, Kentucky, 40241, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68130, United States
Roswell Park Cancer Institute - Medical Oncology
Buffalo, New York, 14263, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15260, United States
Mary Crowley Cancer Research Center
Dallas, Texas, 75251, United States
The University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030, United States
UVA Cancer Center
Charlottesville, Virginia, 22903, United States
VCU Massey Cancer Center
Richmond, Virginia, 23298, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Global Development, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2019
First Posted
May 17, 2019
Study Start
September 3, 2019
Primary Completion
April 19, 2024
Study Completion
April 19, 2024
Last Updated
April 22, 2025
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.