APX005M and Doxorubicin in Advanced Sarcoma

Inclusion Criteria 1. Histologically confirmed advanced soft tissue sarcoma for which doxorubicin treatment is considered appropriate. Patients with well-differentiated liposarcoma who have histologic evidence of a dedifferentiated component are eligible. Kaposi sarcoma and gastrointestinal stromal tumor (GIST) are not eligible. Protocol Amendment 4 restricts further enrollment to participants with the following sarcoma subtypes. A total of 10 patients will be enrolled with each of the following sarcoma subtypes for the entire study, inclusive of patients enrolled prior to Amendment 4: * Dedifferentiated liposarcoma * Leiomyosarcoma * Myxofibrosarcoma/undifferentiated pleomorphic sarcoma 2. Disease must be locally advanced and unresectable or metastatic (that is, considered not amenable to curative surgery or radiation). 3. Patients must have measurable disease by RECIST criteria version 1.1. 4. Patients must demonstrate an ECOG performance status of 0 or 1 and be considered an appropriate candidate for anthracycline chemotherapy. There is no limit on prior lines of systemic therapy received. Treatment naïve patients may be enrolled. 5. Acceptable laboratory parameters: * Absolute neutrophil count (ANC) ≥ 1,500/mm3 * Hemoglobin ≥ 9 g/dL * Platelets ≥ 100,000/mm3 * Creatinine ≤ 1.5 times upper limit of normal OR Calculated creatinine clearance \> 45 mL/min * Total bilirubin ≤ upper limit of normal * AST/ALT ≤ 1.5 times upper limit of normal 6. Patients must have normal left ventricular systolic function, as demonstrated by a transthoracic echocardiogram or MUGA scan at screening, showing a normal left ventricular ejection fraction as defined by the laboratory performing the test. 7. Women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of study drug administration. 8. Ability to understand and willingness to sign a written informed consent document. 9. After the safety lead-in phase is complete, the next consecutive 10 patients enrolled on the study must have a site of tumor tissue which is amenable to image-guided biopsy by interventional radiology with at most minimal risk to the patient. These 10 patients will be required to undergo tumor biopsy at screening and while on-treatment. Exclusion Criteria 1. Patients must not have received treatment with any chemotherapy, immunotherapy, radiotherapy or an investigational agent for malignancy within the 21 days preceding registration. Patients may not have received treatment with a small molecule targeted anti-cancer agent within 14 days preceding study registration, provided this represents at least 7 half-lives for that agent. Furthermore, toxic effects from any prior therapy (except alopecia) must have resolved to ≤ grade 1 by NCI CTCAE v 5.0 or to the patient's baseline by registration. 2. Patients may not be receiving any other investigational agent for any purpose. 3. Patients may not have received prior treatment with: * any anthracycline chemotherapy * CD40 agonist 4. Patients may not have received prior radiotherapy of the mediastinal or pericardial area or whole pelvis radiation. 5. Patients may not have active, known or suspected autoimmune disease with the exceptions of well-controlled: asthma or allergic rhinitis, vitiligo, type 1 diabetes mellitus, psoriasis, or hypothyroidism. 6. Patients may not be receiving chronic systemic steroid therapy in excess of physiologic/ replacement doses (prednisone ≤ 10 mg/day is acceptable), or on any other form of immunosuppressive medication for 14 days prior to registration. 7. Patients with symptomatic brain metastases may not be enrolled. Those subjects with untreated brain metastases ≤ 1 cm who are asymptomatic and for whom there are no plans for surgery, radiation or corticosteroid use may be considered eligible at the discretion of the principal investigator. Subjects with brain metastases that have been treated and are stable for at least 30 days are eligible if asymptomatic and not receiving corticosteroids. Screening for brain metastases is not required and should not be routinely pursued given their uncommon incidence in sarcoma. 8. Patients may not have: * uncontrolled intercurrent illness including, but not limited to congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, uncontrolled diabetes mellitus or uncontrolled psychiatric illness that would limit compliance with study requirements in the opinion of the investigator. * unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months of registration. * any thromboembolic event within 1 month prior to registration * any active coagulopathy * any clinically serious, active infection requiring treatment with antibiotics within 14 days prior to registration * major surgery within 28 days of registration. 9. Patients may not have history of another primary cancer, with the exception of: * curatively treated non-melanomatous skin cancer, * curatively treated cervical carcinoma in-situ, * other primary cancers treated with curative intent, no known active disease and no treatment administered within 2 years prior to registration. * other cancers considered indolent and for which no treatment is anticipated, in the opinion of the principal investigator 10. Patients may not be pregnant or nursing. 11. Patients may not have known HIV or hepatitis A, B or C infection; however, screening tests for these infections are not required.