| Eligibility |
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
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 = 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
- 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
- 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,
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 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.
- 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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