APX005M and Doxorubicin in Advanced Sarcoma

Phase 2

Active, not recruiting

• Conditions: Soft Tissue Sarcoma
• Interventions: Drug: Doxorubicin; Drug: APX005M

• Registration Number: NCT03719430
• Lead Sponsor: Alexander Z. Wei, MD

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.

Detailed Description

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 treatment.

Study Timeline

• Study First Submitted: 2018-10-22
• Study First Submitted QC: 2018-10-23
• Study First Posted: 2018-10-25
• Study Start: 2019-03-20
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Doxorubicin/APX005M	APX005M	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.
Doxorubicin/APX005M	Doxorubicin	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	6 months	The percentage of patients achieving a partial or complete response as measured by imaging assessments from study treatment

Secondary Outcome Measures

Name	Time	Method
Recommended Dose Combination for APX005M and Doxorubicin and Combination Treatment	6 months	A safety-lead in phase will be conducted during which a small number of patients will be treated and monitored closely for certain side effects. If these side effects are seen, the dose of doxorubicin will be adjusted and the study treatment reassessed among another small number of patients. The purpose of the safety lead-in phase is to establish a safe and tolerable dose combination ("the recommended dose") which will be used during the remainder of the study.
Evaluation of Side Effects from APXO05M and Doxorubicin Treatment	18 months	Patients on the study will be assessed at regular intervals during clinical visits and through laboratory testing to monitor side effects from the study treatment.
Progression Free Survival	18 months	The mean time to either disease progression or death, whichever comes first, for patients on the study
Objective Response Rate (ORR)	1 year	Objective response rate in patients with dedifferentiated liposarcoma, leiomyosarcoma, and myxofibrosarcoma/undifferentiated pleomorphic sarcoma. The confirmed ORR per RECIST version 1.1. criteria will be evaluated in the group of patients with these 3 sarcoma subtypes and within each of these subtypes.

Trial Locations

Locations (3)

City of Hope; 🇺🇸 Duarte, California, United States

Washington University School of Medicine - Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Columbia University Irving Medical Center/NYP; 🇺🇸 New York, New York, United States