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

• Spedox-6 (Drug): Given Intravenously (IV)
• Pegfilgrastim (Drug): Given Subcutaneous Injection or IV
• Filgrastim (Drug): Given Subcutaneous Injection or IV

Primary outcomes

• Overall Response Rate (ORR) by RECIST v1.1 [2 Years]: Sum of Complete Response (CR) and Partial Response (PR) by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR
• Disease Control Rate (DCR) by RECIST v1.1 [2 Years]: Disease Control Rate (DCR) defined as Sum of Stable Disease (SD) + Partial Response (PR) + Complete Response (CR) by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD is defined as an increase of at least 20% in the sum of the longest diameters of the target lesions, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD) is defined as a tumor that has neither shrunk sufficiently to qualify as a partial response (PR) nor increased sufficiently to qualify as progressive disease (PD).
• Complete Response Rate by RECIST v1.1 [2 years]: Complete Response Rate assessed by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is defined as the disappearance of all target lesions.
• Partial Response Rate by RECIST v1.1 [2 years]: Partial Response rate assessed by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions

Secondary outcomes

• Stable Disease Rate by RECIST v1.1 [2 years]: Stable Disease Rate by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD is defined as an increase of at least 20% in the sum of the longest diameters of the target lesions, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD) is defined as a tumor that has neither shrunk sufficiently to qualify as a partial response (PR) nor increased sufficiently to qualify as progressive disease (PD).
• Percentage of Responders by RECIST v1.1 [2 years]: Sum of Complete Response (CR) + Partial Response (PR) to determine Percentage of Responders by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Complete Response (CR) is defined as the disappearance of all target lesions. Percentage of Responders (POR) = CR + PR
• Overall Survival [2 years]: Survival rate of subjects who received at least one dose of Spedox-6.
• Progression Free Survival [2 years]: Survival rate of subjects who received at least one dose of Spedox-6 without Progression of their disease.
• Number of Patients with Grade 3 non-hematological toxicities by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [2 years]: Number of Patients who received at least one dose of Spedox-6 with Grade 3 non-hematological toxicities (excluding alopecia) by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 with the following exceptions: Grade 3 nausea/vomiting or diarrhea <72 hours with adequate antiemetic and other supportive care; Grade 3 fatigue <1 week; Grade 3 electrolyte abnormality that lasts up to 72 hours, is not clinically complicated and resolves spontaneously or responds to conventional medical interventions.
• Number of patients with Grade 4 non-hematologic (non-laboratory) by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [2 years]: Number of patients who received at least one dose of Spedox-6 with Grade 4 non-hematologic (non-laboratory) toxicity of any duration per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Number of patients with Grade 3 or Grade 4 febrile neutropenia by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [2 years]: Number of patients who received at least one dose of Spedox-6 with Grade 3 or Grade 4 febrile neutropenia of any duration per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Number of patients with Grade 3 Thrombocytopenia in Combination with Grade 3 or greater blood and lymphatic system disorder by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [2 years]: Number of patients who received at least one dose of Spedox-6 with Grade 3 Thrombocytopenia in Combination with Grade 3 or greater blood and lymphatic system disorder per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Number of patients with Grade 3 AST or ALT increase that is associated with a Grade 2 or greater Rise in Bilirubin by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [2 years]: Number of patients who received at least one dose of Spedox-6 with Grade 3 AST or ALT increase that is associated with a Grade 2 or greater Rise in Bilirubin per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Other outcomes

• Correlation between Tumor FcRn Expression (IHC Score) and Objective Response (per RECIST v1.1) [2 years]: E valuate the correlation between tumor neonatal Fc receptor (FcRn) expression, as measured by immunohistochemistry (IHC) H-score, and objective tumor response, defined per RECIST v1.1 criteria (Complete Response or Partial Response).
• Correlation between Tumor FcRn Expression (IHC Score) and Disease Control (CR + PR + SD per RECIST v1.1) [2 years]: To evaluate the correlation between tumor neonatal Fc receptor (FcRn) expression, as assessed by immunohistochemistry (IHC) H-score, and disease control, defined as the proportion of patients achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Subjects ≥ 18 years at the first screening examination/visit.
* Subjects with advanced histologically or cytologically confirmed solid tumors (see below) refractory to or relapse from at least two previous therapies.
* Tumor types expected to express lower levels of FcRn relative to normal tissue including: STS, TNBC, cervical cancer, NSCLC, ovarian cancer, and KRAS mutated pancreatic 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 on established antiretroviral therapy (ART) for at least four weeks and have an HIV viral 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 Alanine Aminotransferase (ALT) ≤3x ULN, and creatinine clearance >50 mL/min as assessed by Cockcroft-Gault equation.
* For patients with known Gilbert's disease, serum unconjugated bilirubin must be < 4 mg/dL.
* Patient must have washed out of prior chemotherapy (at least 3 weeks from last end of 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 4 weeks from last end of therapy), or surgery (at least 4 weeks).
* Recovery from toxicities of prior therapy. Toxicities should have recovered to CTCAE grade ≤ 1 or baseline with exception of alopecia.
* Females of reproductive potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment. Additionally, female subjects of reproductive potential should agree to use effective acceptable forms of contraception: surgical sterilization (tubal ligation); total abstinence from sexual intercourse 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 month prior to Cycle 1 Day 1 and agreement to use such a method during study participation and 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 after the last dose of SPEDOX-6.

Exclusion Criteria:

* Patients with cancers with known driver mutations for which there are known and effective targeted therapies that have not received those therapies, but are able to. If a patient has received appropriate targeted treatment for their mutations and progressed, or those treatments are contraindicated, they will be considered potentially eligible.
* Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months 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 drug or 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).

• Warren Chow, MD, Principal investigator, Chao Family Comprehensive Cancer Center