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

  • End date
    Oct 31, 2024
  • participants needed
  • sponsor
    Astellas Pharma Global Development, Inc.
Updated on 25 October 2022
measurable disease
solid tumor
solid neoplasm


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.


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. In dose escalation part only ASP9801 will be assessed. In dose expansion part along with ASP9801 (monotherapy) ASP9801 + Pembrolizumab (combination therapy) will be assessed. 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).

Condition Metastatic Cancer, Solid Tumors, Advanced Cancer
Treatment Pembrolizumab, ASP9801
Clinical Study IdentifierNCT03954067
SponsorAstellas Pharma Global Development, Inc.
Last Modified on25 October 2022


Yes No Not Sure

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 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
Female subject must not donate ova starting at screening, and throughout the study period and for 180 days after the final study IP administration
study period and 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 ≥ 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 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
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
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
Leukocytes < 3000/μL
Absolute neutrophil count < 1500/μL
Platelets < 100,000/μL
Hemoglobin (Hgb) < 9 g/dL (Criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Subjects can be on stable dose of erythropoietin [≥ approximately 3 months])
International normalized ratio (INR) > 1.5 × ULN and/or activated partial thromboplastin time (aPTT) > 1.5 × institutional normal limits, except for subjects 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) > 2.5 × institutional normal limits. Subjects with tumors in the liver AST and ALT > 5 × institutional normal limits
Albumin < 3.0 g/dL
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
Creatinine > 1.5 × institutional normal limits
Subject has an uncontrolled intercurrent illness including, but not limited to, 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 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 is 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 clinically significant abnormal electrocardiogram (ECG) at screening
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 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 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
Subject has an active infection requiring systemic therapy
Subject with known history of active Bacillus Tuberculosis
Subject has received prior therapy with an anti-PD-1, anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4, OX 40, CD137) and was discontinued from that treatment due to an immune-related adverse event
Subject has received prior radiation therapy within 2 weeks of start of study treatment. Subject must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease
Subject has received a live vaccine within 30 days prior to the first dose of study drug
Examples of live vaccines include, but are not limited to, the following: measles, mumps
rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette-Guérin and
typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus
vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live
attenuated vaccines and are not allowed
Subject has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its
excipients, or history of ≥ grade 2 infusion reactions that were not prevented by
adequate premedication
Subject has a history of (non-infectious) pneumonitis that required steroids or has
current pneumonitis
Subject has had an allogeneic tissue/solid organ transplant
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