APX005M and Doxorubicin in Advanced Sarcoma

NCT03719430 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAS0095
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Soft Tissue Sarcoma

Keywords

Leiomyosarcoma; Liposarcoma; Pleomorphic sarcoma; Synovial sarcoma; Malignant peripheral nerve sheath tumor; Spindle cell sarcoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The percentage of patients achieving a partial or complete response as measured by imaging assessments from study treatment

  6 months

Secondary Outcomes (4)

• Recommended Dose Combination for APX005M and Doxorubicin and Combination Treatment

  6 months

• Evaluation of Side Effects from APXO05M and Doxorubicin Treatment

  18 months

• Progression Free Survival

  18 months

• Objective Response Rate (ORR)

  1 year

Other Outcomes (2)

• Changes in Immune Cell Infiltrates in Baseline and On-Study Biopsies

  18 months

• Expression of CD40 in Baseline Study Biopsies

  18 months

Study Arms (1)

Doxorubicin/APX005M

EXPERIMENTAL

Patients will be treated with doxorubicin and APX005M in 21 day cycles. All patients receive the same treatment (there is no "placebo" arm). After completing 8 cycles of study treatment, patients without evidence of disease progression or unacceptable toxicity may continue treatment with APX005M alone. Doxorubicin will not be continued beyond cycle 8 due to the risk for cardiac toxicity from cumulative dosing.

Drug: Doxorubicin; Drug: APX005M

Interventions

Doxorubicin DRUG

Doxorubicin is an anthracycline antibiotic with antineoplastic activity 75 mg/m2 IV day 1 (21 day cycles)

Also known as: ADRIAMYCIN

Doxorubicin/APX005M

APX005M DRUG

APX005M is a CD40 agonistic monoclonal antibody 0.3 mg/kg IV day 1 (21 day cycles)

Also known as: APX-005M

Doxorubicin/APX005M

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Disease must be locally advanced and unresectable or metastatic (that is, considered not amenable to curative surgery or radiation).
• Patients must have measurable disease by RECIST criteria version 1.1.
• 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.
• 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
• 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.

You may not qualify if:

• 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.
• Patients may not be receiving any other investigational agent for any purpose.
• Patients may not have received prior treatment with:
• any anthracycline chemotherapy
• CD40 agonist
• Patients may not have received prior radiotherapy of the mediastinal or pericardial area or whole pelvis radiation.
• 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.
• 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.
• 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.
• 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

Sponsors & Collaborators

• Alexander Z. Wei, MD: lead
• Apexigen America, Inc.: collaborator

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Columbia University Irving Medical Center/NYP

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Sarcoma; Leiomyosarcoma; Liposarcoma; Sarcoma, Synovial; Neurofibrosarcoma

Interventions

Doxorubicin; sotigalimab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Neoplasms, Adipose Tissue; Neoplasms, Connective Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Alexander Wei, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 25, 2018
• Study Start: March 20, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)