This is a multi-center, open-label, single-arm study that in Phase 1b will determine the
maximum tolerated dose (MTD)/ recommended phase 2 dose (RP2D) and safety of L-Annamycin and
in Phase 2 will explore the efficacy of L- Annamycin as a single agent for the treatment of
subjects with STS with lung metastases for which chemotherapy is considered appropriate.
1. The subject has a pathologically confirmed diagnosis of STS and documented lung
metastases that are considered eligible for chemotherapy and not eligible for
potentially curative surgical resection of pulmonary-only metastatic disease.
2. The subject had prior anthracycline therapy (cumulative dose of ≤450 mg/m2) for their
disease and has shown progression of disease prior to study entry.
3. The subject must have measurable disease in the lung, defined as at a minimum, 1
lesion that can be accurately measured in at least one dimension of >10 mm. Subjects
with extra-pulmonary disease are eligible.
4. The subject has an estimated life expectancy of greater than 3 months.
5. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. The subject is ≥18 years old at the time of signing informed consent.
7. At least 2 weeks must have passed following treatment for their disease with
chemotherapy, investigational therapy, targeted agents, biological agents, immune
modulators, or radiotherapy, and any toxicities must have resolved to ≤ grade 1 or
previous baseline levels no more than 4 weeks after completing therapy (except
alopecia and polyneuropathy).
8. The subject must have adequate laboratory results including the following:
1. Absolute neutrophil count ≥ 1500/mL and platelets ≥100,000/mL
2. Hemoglobin ≥ 8.0 g/dL
3. Adequate renal function (The Cockcroft-Gault equation will be used to estimate
creatinine clearance. This equation is as follows: Creatinine clearance in
milliliters per minute = [140-age] x body weight [kg]/72 x plasma creatinine
[mg/dL]; multiplied by 0.85 for women. By using this equation, adequate renal
function will be deemed to be a creatinine clearance of greater than 60
4. Bilirubin ≤1.5 x upper limit of normal (ULN) (unless due to Gilbert's syndrome)
5. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and/or
alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 × ULN (≤ 5 x
ULN in subjects with liver metastases)
9. The subject is able to understand and sign the informed consent document, can
communicate with the Investigator, and can understand and comply with the requirements
of the protocol.
10. All subjects (men and women) agree to practice effective contraception during the
entire study period and after discontinuing study drug, unless documentation of
1. Sexually active, fertile women must use 2 effective forms of contraception
(abstinence, intrauterine device, oral contraceptive, or double barrier device)
from the time of informed consent and until at least 6 months after discontinuing
2. Sexually active men and their sexual partners must use effective contraceptive
methods from the time of informed consent until at least 6 months after
discontinuing study drug
1. The subject has any condition that, in the opinion of the Investigator, places the
subject at unacceptable risk if they were to participate in the study.
2. The subject has left ventricular ejection fraction (LVEF) <50%, valvular heart
disease, or severe hypertension not controlled by medical therapy. Cardiac subjects
with a New York Heart Association classification of 3 or 4 will be excluded, as will
those with recent (≤ 6 months) myocardial infarction, unstable angina, or symptomatic
congestive heart failure.
3. The subject has a baseline QT/QTc interval >480 msec, a history of additional risk
factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of
Long QT Syndrome) and use of concomitant medications that significantly prolong the
4. The subject has clinically relevant serious comorbid medical conditions including, but
not limited to active infection, known positive status for human immunodeficiency
virus or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations
that would limit compliance with study requirements.
5. The subject is pregnant, lactating, or not using adequate contraception.
6. The subject has a known allergy to study drug or excipients.
7. The subject is required to use moderate or strong inhibitors and inducers of
Cytochrome P450 family enzymes CYP3A and CYP2B and transporters that cannot be held 3
days before treatment and on the day of treatment.