A Study of Talimogene Laherparepvec (T-VEC) in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma

Inclusion Criteria:

- Male or female age ≥ 18 years at the time of informed consent

- Be willing and able to provide written informed consent/assent for the trial

- Be willing to comply with treatment protocol

- Subjects must have a histologically confirmed metastatic and/or locally advanced
sarcoma

- Subjects must have at least 1 injectable cutaneous, subcutaneous soft tissue or nodal
lesion ≥ 10 mm in longest diameter. Of note, bone lesions are not eligible for
injection unless there is a soft tissue component that is amenable to injection.
Injectable lesions must not be chosen from a previously irradiated field unless there
has been radiographically and/or pathologically documented tumor progression in that
lesion prior to enrollment

- Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy,
immunotherapy, targeted or biological therapy) for their sarcoma. An exception to this
criterion will be made for patients with sarcoma histological subtypes for which there
is no known standard systemic therapy (e.g., chondrosarcoma). Prior adjuvant therapy
will not count provided it was completed more than 6 months previously

- Subjects must have measurable disease (at least one target lesion) as defined by
RECIST 1.1. Target lesions must not be chosen from a previously irradiated field
unless there has been radiographically and/or pathologically documented tumor
progression in that lesion prior to enrollment

- Adequate performance status: ECOG 0 or 1/KPS 100-70%

- Adequate organ function determined within 3 weeks of treatment initiation, defined as
follows:

- I. Hemoglobin ≥ 8.0 g/dl

- II. Absolute neutrophil count ≥ 1,000/mm^3 (1.0 x 10^9/L)

- III. Platelet count ≥ 75,000/mm3 (75 x 109/L)

- IV. Serum bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total
bilirubin level > 1.5 x ULN

- V. Aspartate aminotransferase (AST) ≤ 2.5 x ULN OR ≤ 5 x ULN for subjects with liver
metastases

- VI. Alanine aminotransferase (ALT) ≤ 2.5 x ULN OR ≤ 5 x ULN for subjects with liver
metastases

- VII. Alkaline Phosphatase < 5 x ULN

- VIII. Albumin ≥2.5mg/dL

- IX. Serum creatinine ≤ 1.5 x ULN or a measured or calculateda* creatinine clearance ≥
60mL/min for subject with creatinine levels > 1.5 x institutional ULN (Note:
Creatinine clearance need not be determined if the baseline serum creatinine is within
normal limits. GFR can also be used in place of creatinine or CrCl) X. International
Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants XI. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless
subject is receiving anticoagulant therapy as long as PT and PTT is within therapeutic
range of intended use of anticoagulants

*aCreatinine clearance should be calculated per institutional standard

- Female subject of childbearing potential should have a negative serum pregnancy
testing at screening visit and within 72 hours prior to the first dose of study
medication

Exclusion Criteria:

- Uncontrolled intercurrent illness including active infection requiring systemic
therapy or symptomatic congestive heart failure within 6 months

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability

- Evidence of clinically significant immunosuppression such as the following:

- Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

- Concurrent opportunistic infection

- Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
doses > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment.
However, in the setting of non-immune mediated indications for use,
chronic/active low dose steroid use may be permitted at the discretion of the
principal investigator

- Known history of human immunodeficiency virus (HIV) disease

- History or evidence of symptomatic autoimmune disease (e.g., pneumonitis,
glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive
drugs or biological agents used for treatment of autoimmune diseases) in past 2 years
prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin
for diabetes or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency) is not considered a form of systemic treatment for autoimmune
disease

- Active herpetic skin lesions or prior complications of herpetic infection

- Require intermittent or chronic treatment with an intravenous or oral antiherpetic
drug (e.g., acyclovir), other than intermittent topical use

- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected)

- Received live vaccine within 28 days prior to enrollment. Note: Seasonal influenza
vaccines for injection are generally inactivated flu vaccines and are allowed; however
intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are
not allowed

- Has a known history of active TB (Bacillus Tuberculosis)

- Female subject is pregnant or breast-feeding, or planning to become pregnant or male
subject is planning to father a child within the projected duration of the trial,
starting with the pre-screening or screening visit, during study treatment and through
3 months after the last dose of talimogene laherparepvec or 4 months after the last
dose of pembrolizumab, whichever is later

- Male and female subjects of childbearing potential who are unwilling to use acceptable
method(s) of effective contraception during study treatment and through 3 months after
the last dose of talimogene laherparepvec and 4 months after the last dose of
pemrolizumab. (Note: Women not of childbearing potential are defined as: Any female
who is post-menopausal [age > 55 years with cessation of menses for 12 or more months
or less than 55 years but not spontaneous menses for at least 2 years or less than 55
years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g.,
spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels
(luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or
postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of
"postmenopausal range" for the laboratory involved] or who have had a hysterectomy,
bilateral salpingectomy, or bilateral oophorectomy)

- Sexually active subjects and their partners unwilling to use male or female latex
condom to avoid potential viral transmission during sexual contact while on treatment
and within 30days after treatment with talimogene laherparepvec

- Subject who is unwilling to minimize exposure with his/her blood or other body fluids
to individuals who are at higher risks for HSV-1 induced complications such as
immunosuppressed individuals, individuals known to have HIV infection, pregnant women,
or children under the age of 1 year, during talimogene laherparepvec treatment and
through 30 days after the last dose of talimogene laherparepvec

- Known previous history of sensitivity to talimogene laherparepvec or any of its
components to be administered during dosing (e.g. sorbitol, myo-inositol)

- Hypersensitivity to pembrolizumab or any of its excipients

- Prior therapy with talimogene laherparepvec, tumor vaccine

- Prior chemotherapy, radiotherapy, biological cancer therapy, targeted small molecule
therapy or major surgery within 21 days prior to study Day 1 or who has not recovered
(i.e., to CTCAE ≤ grade 1 or at baseline) from adverse events due to previously
administered therapy. Note: Subjects with ≤ grade 2 neuropathy and alopecia are an
exception to this criterion and may qualify for the study. Note: If subject received
major surgery, they must have recovered adequately from the toxicity and/or
complications from the intervention prior to starting therapy

- Is currently participating and receiving study therapy with another investigational
device or study drug or has participated in a study of an investigational agent and
received study therapy or used an investigational device within 3 weeks of the first
dose of treatment

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

- The presence of any other concurrent active malignancy