Trial of Single Protein Encapsulated Doxorubicin, SPEDOX-6 in Advanced Malignancies

Inclusion Criteria:

• Subjects ≥ 18 years at the first screening examination/visit.

• Subjects with advanced histologically or cytologically confirmed solid tumors (seebelow) refractory to or relapse from at least two previous therapies.

• Tumor types expected to express lower levels of FcRn relative to normal tissueincluding: STS, TNBC, cervical cancer, NSCLC, ovarian cancer, and KRAS mutatedpancreatic ductal adenocarcinoma without requirement for testing FcRn level.

• Disease that is considered measurable by RECIST v1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

• Life expectancy of at least 12 weeks.

• Human Immunodeficiency Virus (HIV)-positive trial participants should be onestablished antiretroviral therapy (ART) for at least four weeks and have an HIVviral load less than 400 copies/mL prior to enrollment.

• Left ventricular ejection fraction > 50%.

• Adequate organ function: (Hb ≥10 g/dL, ANC ≥1,000/µL3, and platelets

≥100,000/µL3), serum bilirubin ≤.5x the institutional upper limit of normal (ULN) (unless known Gilbert's disease), Aspartate Aminotransferase (AST) and AlanineAminotransferase (ALT) ≤3x ULN, and creatinine clearance >50 mL/min as assessed byCockcroft-Gault equation.

• For patients with known Gilbert's disease, serum unconjugated bilirubin must be < 4mg/dL.

• Patient must have washed out of prior chemotherapy (at least 3 weeks from last endof therapy), radiotherapy (at least 4 weeks from last end of therapy), immunotherapy (at least 4 weeks from last end of therapy), other targeted therapies (at least 4weeks from last end of therapy), or surgery (at least 4 weeks).

• Recovery from toxicities of prior therapy. Toxicities should have recovered to CTCAEgrade ≤ 1 or baseline with exception of alopecia.

• Females of reproductive potential must have had a negative pregnancy test performedwithin 7 days prior to the start of treatment. Additionally, female subjects ofreproductive potential should agree to use effective acceptable forms ofcontraception: surgical sterilization (tubal ligation); total abstinence from sexualintercourse with the opposite sex; established hormonal birth control (e.g., oral,transdermal, injection, or implant) plus a barrier method or a double barrier method (intrauterine device, spermicide, or a diaphragm plus condom) for at least 1 monthprior to Cycle 1 Day 1 and agreement to use such a method during study participationand for an additional 6 months after the last dose of SPEDOX-6.

• For males of reproductive potential: vasectomy or highly effective contraception (e.g., condoms, abstinence) during the study and for an additional 6 months afterthe last dose of SPEDOX-6.

Exclusion Criteria:

• Patients with cancers with known driver mutations for which there are known andeffective targeted therapies that have not received those therapies, but are ableto. If a patient has received appropriate targeted treatment for their mutations andprogressed, or those treatments are contraindicated, they will be consideredpotentially eligible.

• Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6months before study entry.

• Untreated metastases to the Central Nervous System (CNS).

• Have received any prior doxorubicin or anthracycline equivalent.

• Previous radiation to the mediastinal or pericardial area.

• A known allergy to albumin.

• HIV infection with CD4+ count < 350 cells/µL or Acquired Immunodeficiency (AIDS)-defining opportunistic infection in previous 12 months.

• Pregnant (positive serum or urine pregnancy test) or lactating.

• Previous treatment with an investigational agent or the non-approved use of a drugor device withing 4 weeks of study entry.

• Uncontrolled diabetes mellitus.

• Patients who require concomitant use of strong inhibitors or inducers of CYP3A4,CYP2D6 or P-glycoprotein (P-gp).