A PHASE IB/II STUDY TO EVALUATE SAFETY AND EFFICACY OF BEXMARILIMAB IN COMBINATION WITH DOXORUBICIN IN METASTATIC SOFT-TISSUE SARCOMA

NCT07460986 | Not Yet Recruiting Phase 1

• 1 other identifier: MedOPP0799
• Study Type: interventional
• Target: 278
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial will Study a type of sarcoma defined metastatic soft-tissue sarcoma (STS). Participants will be treated with bexmarilimab, a CLEVER-1 antibody plus doxorubicin, a chemotherapy. The main purpose of the Study is to analyze the safety (to find out how safe or toxic a treatment is to appropriately manage the risks) and efficacy (to find out how effective a treatment is) of bexmarilimab combined with doxorubicin in participants who have STS.

Conditions

Sarcoma of Soft Tissue

Keywords

Soft Tissue Sarcoma, Clever-1, Bexmarilimab

Outcome Measures

Primary Outcomes (2)

• Phase Ib: MTD and RP2D

  The MTD and RP2D of bexmarilimab when used in combination with doxorubicin will be reported based upon evaluation of dose-limiting toxicities (DLTs) and adverse events (AEs) and other available data from secondary endpoints.

  Up to 14 months

• Phase II: PFS

  PFS, defined as the period from treatment randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the Investigator using RECIST v1.1.

  Up to 36 months

Secondary Outcomes (9)

• Phase Ib: 6-months PFS

  6 months

• ORR

  Up to 36 months

• CBR

  Up to 36 months

• TTR

  Up to 36 months

• DoR

  Up to 36 months

Study Arms (4)

Phase II: Arm A

EXPERIMENTAL

Participants will be randomized based on histological subtype, age (≥ 60 years old vs \<60 years old) and ECOG status (0 vs 1) to receive RP2D of bexmarilimab plus doxorubicin (arm A) for 6 cycles. Then, participants will receive RP2D of bexmarilimab monotherapy (arm A) until unacceptable toxicity, disease progression, death, discontinuation from the Study treatment for any other reason, whichever occurs first.

Drug: bexmarilimab; Drug: Doxorubicin

Phase II: Arm B

ACTIVE COMPARATOR

Participants will be randomized based on histological subtype, age (≥ 60 years old vs \<60 years old) and ECOG status (0 vs 1) to receive doxorubicin monotherapy (arm B).

Drug: Doxorubicin

Phase Ib: Dose escalation

EXPERIMENTAL

Participants will receive 3 different doses (1 mg/kg, 3 mg/kg or 6 mg/kg) of bexmarilimab administered as IV infusion on day 1 (D1) of each 21-day cycle plus 75 mg/m2 doxorubicin administered as IV infusion on D1 of 21-day cycle in order to find the RP2D for bexmarilimab when administered in combination with doxorubicin.

Drug: bexmarilimab; Drug: Doxorubicin

Phase Ib: Dose expansion

EXPERIMENTAL

Participants will be randomized based on histological subtype to receive receive 2 different doses (based on dose escalation data) of bexmarilimab plus doxorubicin for 6 cycles. Then, participants will receive RP2D of bexmarilimab monotherapy until unacceptable toxicity, disease progression, death, discontinuation from the Study treatment for any other reason, whichever occurs first.

Drug: bexmarilimab; Drug: Doxorubicin

Interventions

bexmarilimab DRUG

RP2D of bexmarilimab administered as IV infusion on D1 of 21-day cycle for 6 cycles.

Phase II: Arm A; Phase Ib: Dose escalation; Phase Ib: Dose expansion

Doxorubicin DRUG

75 mg/m2 doxorubicin administered as IV infusion on D1 of 21-day cycle for 6 cycles.

Phase II: Arm A; Phase II: Arm B; Phase Ib: Dose escalation; Phase Ib: Dose expansion

Eligibility Criteria

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

You may qualify if:

• Participant, or legal representative (if applicable), must be capable to understand the purpose of the Study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
• Female or male participants ≥ 18 years of age at the time of signing ICF.
• For phase Ib (dose escalation):
• Histologically documented metastatic STS with no more than 3 lines of treatment.
• Participant has not received doxorubicin, but doxorubicin could be indicated for metastatic disease as per institutional guidelines.
• For phase Ib (dose expansion) and for phase II:
• Metastatic STS with any of the following histologies: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), dedifferentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), leiomiosarcoma (LMS) with no prior treatment in the advanced setting. Capped to 33% of participants with UPS/MFS, 33% of participants with DDLPS/MLPS, and 33% of participants with LMS.
• Measurable disease according to RECIST v.1.1.
• Participant has adequate bone marrow, liver, and renal function:
• Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within 7 days before first Study treatment dose): Absolute neutrophil count (ANC) ≥ 1,000/mm3, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9.0 g/dL.
• Hepatic: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 ×ULN if Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 ×ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 ×ULN in participants with no liver metastasis and 5.0 ×ULN in participants with liver metastasis; partial thromboplastin \[PT\]-INR/activated partial thromboplastin time \[PTT\] \<1.5×ULN (≤ 2.0×ULN for participants on anticoagulation prophylactic regimen).
• Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min/1.73 m2 based on Cockcroft-Gault glomerular filtration rate estimation for participants with creatinine levels above institutional normal.
• Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 (v.6.0) (except for alopecia or other toxicities not considered a safety risk for the participant at investigator's discretion).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Minimum life expectancy of ≥ 12 weeks at screening.

You may not qualify if:

• Participation in another clinical trial, interventional or observational, until the Study's safety visit. Note: participation in retrospective studies or data analysis is allowed.
• Treatment with approved or investigational cancer therapy within 14 days prior to initiation of Study drug.
• Prior treatment with anthracyclines for localized or advanced disease.
• Prior treatment with immunocheckpoint inhibitors for localized or advanced disease.
• For phase Ib (dose expansion) and phase II: participant has received prior treatment in the advanced setting.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before randomization to rule out brain metastasis.
• Participants diagnosed with bone sarcomas, locally-aggressive sarcomas, GIST or Kaposi sarcoma.
• Have a concurrent malignancy or malignancy within 5 years of Study enrollment with the exception of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
• Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.
• Major surgical procedure or significant traumatic injury within 14 days before the first dose of Study treatment or anticipation of need for major surgery within the course of the Study treatment.
• The patient requires systemic corticosteroid (≥10 mg/day prednisone or equivalent) or other immunosuppressive treatment. Topical, nasal, inhaled, and ophthalmic corticosteroids are allowed.
• Has an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including, but not confined, to any of the following:
• History and/or signs of active coronary artery disease/ischemia with or without angina pectoris, documented myocardial infarction, or symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] Class II-IV) within six months prior to Study entry.
• Symptomatic pericarditis.
• Left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).

Sponsors & Collaborators

• MedSIR: lead
• Faron Pharmaceuticals Ltd: collaborator

MeSH Terms

Conditions

Sarcoma

Interventions

bexmarilimab; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 10, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03