This phase II clinical trial will evaluate the safety and efficacy of adding APX005M (a CD40
agonistic monoclonal antibody) to doxorubicin for the treatment of patients with advanced
soft tissue sarcoma. The investigators believe that doxorubicin, which is currently the
standard of care for most advanced sarcomas, could work better when combined with APX005M,
which is a type of immunotherapy.
Doxorubicin, a chemotherapy, is currently considered standard-of-care treatment for most
advanced soft tissue sarcomas. This study will assess the safety and efficacy of combining
APX005M, a novel immunomodulatory drug, together with standard of care doxorubicin, for the
treatment of patients with advanced soft tissue sarcoma. APX005M is an agonistic monoclonal
antibody targeting the CD40 receptor and may have favorable effects on certain types of
immune cells in sarcoma tumors, particularly macrophages.
The primary objective is to determine the objective response rate. Secondary objectives
include further evaluation of safety and efficacy. A subset of patients will undergo tumor
biopsies at baseline and while on study treatment to help understand how the drug combination
works and to evaluate how the composition of immune cells in the tumor changes after the
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.
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 >
- 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.
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.