| Eligibility |
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
- Adequate performance status: ECOG 0 or 1/KPS 100-70%
- 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). Any patient that refuses
standard chemotherapy for the treatment of their disease is also considered eligible.
Prior adjuvant therapy will not count provided it was completed more than 6 months
previously.
- Presence of measureable disease per RECIST v1.1.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.
- All subjects must agree to pre-treatment tumor biopsy. Subjects in whom biopsy is
technically not feasible or in whom would result in unacceptable risk, in the opinion
of the investigator, may be exempted from the biopsy requirement with discussion with
the principal investigator.
- Adequate organ function determined within 21 days of treatment initiation
- Hematological
- Absolute neutrophil count (ANC) =1,000 /mcL
- Platelets =75,000 / mcL
- Hemoglobin =8 g/dL or =5.0 mmol/L
- Renal
°Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be
used in place of creatinine or CrCl) =1.5 X upper limit of normal (ULN) OR
=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN aCreatinine
clearance should be calculated per institutional standard.
- Hepatic
- Serum total bilirubin = 1.5 X ULN OR Direct bilirubin = ULN for subjects with
total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) = 2.5 X ULN OR = 5 X ULN for subjects with liver
metastases
- Albumin = 2.5 mg/dL
- Coagulation
- International Normalized Ratio 52 or Prothrombin Time =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
- Activated Partial Thromboplastin Time (aPTT) =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
- Women of childbearing potential must have a negative serum pregnancy test at screening
and = 72 hours prior to day 1 of study treatment.
- Male and female subjects of childbearing potential must be willing to use an adequate
method of contraception as outlined in Section 11.7, for the course of the study
through 120 days after the last dose of study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
Exclusion Criteria:
- Uncontrolled intercurrent illness including current 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 steroid use,
chronic/active low dose steroid use may be permitted at the discretion of the
principal investigator. The dose of steroid allowed in this setting is also at
the discretion of the principal investigator. (Use of inhaled or topical steroids
is permitted.)
- 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.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) disease
- Has known active Hepatitis B (e.g., Hepatitis B Virus PCR is detected) or Hepatitis C
(e.g., HCV RNA [qualitative] is detected).
- Patients who have received a live vaccine within 30 days of the start date of the
planned study therapy. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. 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)
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 2 weeks of the first dose of treatment.
- Has had a prior chemotherapy, immunotherapy, biological therapy, targeted small
molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has
not recovered (i.e., = Grade 1 or at baseline) from adverse events due to previously
administered agent.
- Note: Subjects with = Grade 2 neuropathy, alopecia or hypothyroidism 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
events due to a previously administered agent.
- Presence of a gastrointestinal condition that may affect drug absorption
- Known allergy or reaction to any component of either study drug formulation
- Women who are pregnant or breast feeding
- Subjects expecting to conceive or father children within the projected duration of the
trial, starting with the pre-screening or screening visit through 120 days after the
last dose of study treatment(s).
- Inability to comply with protocol required procedures
- Subjects receiving Monoamine Oxidase Inhibitors (MAOIs) or drug which has significant
MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before
screening.
- Any history of Serotonin Syndrome (SS) after receiving serotonergic drugs.
- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's
opinion, is clinically meaningful. Screening QTc interval 480 milliseconds is
excluded. In the event that a single QTc is = 480 milliseconds, the subject may enroll
if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an
intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval
may be used in place of the QTc with the approval of the principal investigator. The
JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left
bundle branch block are excluded.
Note: QTc prolongation due to pacemaker may enroll if the JTc is normal.
- Use of any UGT1A9 inhibitor from screening through follow-up period, including the
following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid.
- History of prior therapy with an IDO1 inhibitor in combination with an
anti-PD-1/anti-PD-L1 agent/any other drug specifically targeting checkpoint pathways.
Patients who have received prior therapy with single agent anti-PD-1/anti-PD-L1
therapy or single agent IDO1 inhibitor will be eligible for this study.
- Presence of any other concurrent active malignancy
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