Bintrafusp Alfa and Doxorubicin Hydrochloride in Treating Patients With Advanced Sarcoma

NCT04874311 | Recruiting Phase 2 DMC

• 2 other identifiers: IB 2020-052020-005703-39
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 8

Brief Summary

This study encompasses two multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trials to assess the antitumor activity of bintrafusp alfa in association with doxorubicin

Conditions

Advanced Soft-tissue Sarcoma; Metastatic Soft-tissue Sarcoma

Keywords

tertiary lymphoid structure; soft-tissue sarcoma; advanced/metastatic; immunotherapy

Outcome Measures

Primary Outcomes (2)

• Assessment of the antitumor activity of combined administration of standard doxorubicin and double immune modulation with Bintrafusp alfa in terms of 6-month progression-free rate, in STS patients with an inflammed tumor

  Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.

  6 months

• Assessment of the antitumor activity of combined administration of standard doxorubicin and double immune modulation with Bintrafusp alfa in terms of 6-month progression-free rate, in STS patients with a cold tumor

  Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.

  6 months

Secondary Outcomes (11)

• 6-month objective response rate (ORR) independently for patients with an inflammed tumor

  6 months

• 6-month objective response rate (ORR) independently for patients with a cold tumor

  6 months

• Best overall response for patients with an inflammed tumor

  throughout the treatment period, an expected average of 6 months

• Best overall response for patients with a cold tumor

  throughout the treatment period, an expected average of 6 months

• 1-year progression-free survival for patients with an inflammed tumor

  1 year

Other Outcomes (4)

• Tumor immune cells levels independently for each population

  baseline, cycle 2 day 1, and progression (each cycle is 21 days)

• Blood cytokines levels independently for each population

  baseline, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)

• Blood lymphocytes levels independently for each population

  baseline, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)

Study Arms (4)

Experimental Arm A: treatment by bintrafusp alfa combined with doxorubicin

EXPERIMENTAL

Soft-tissue sarcoma patients with an inflammed tumor will be treated with bintrafusp alfa combined with doxorubicin for 6 cycles, followed by bintrafusp alfa maintenance

Drug: Bintrafusp alfa; Drug: Doxorubicin

Standard Arm B: treatment by doxorubicin

OTHER

Soft-tissue sarcoma patients with an inflammed tumor will be treated with doxorubicin for 6 cycles

Drug: Doxorubicin

Experimental Arm C: treatment by bintrafusp alfa combined with doxorubicin

EXPERIMENTAL

Soft-tissue sarcoma patients with a cold tumor will be treated with bintrafusp alfa combined with doxorubicin for 6 cycles, followed by bintrafusp alfa maintenance

Drug: Bintrafusp alfa; Drug: Doxorubicin

Standard Arm D: treatment by doxorubicin

OTHER

Soft-tissue sarcoma patients with a cold tumor will be treated with doxorubicin for 6 cycles

Drug: Doxorubicin

Interventions

Bintrafusp alfa DRUG

Bintrafusp alfa will be administered by intravenous infusion on day 1 every 3 weeks at a fixed dose of 2400 mg.

Experimental Arm A: treatment by bintrafusp alfa combined with doxorubicin; Experimental Arm C: treatment by bintrafusp alfa combined with doxorubicin

Doxorubicin DRUG

Doxorubicin will be administered by intravenous infusion on day 1 every 3 weeks at a fixed dose of 75 mg/m² for a maximum of 6 cycles

Experimental Arm A: treatment by bintrafusp alfa combined with doxorubicin; Experimental Arm C: treatment by bintrafusp alfa combined with doxorubicin; Standard Arm B: treatment by doxorubicin; Standard Arm D: treatment by doxorubicin

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed soft-tissue sarcoma with unknown translocation (including the following histologies but not limited to undifferentiated pleomorphic sarcomas, dedifferentiated liposaromas or leiomyosarcomas). Diagnosis must be reviewed or confirmed by the RRePS Network (Réseau de référence en pathologie des sarcomes et des viscères) as recommended by the French NCI (Institut National du Cancer, Inca).
• Metastatic or unresectable locally advanced disease,
• No previous systemic treatment for advanced/metastatic disease,
• For TLS status: available archived FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample or tumor material newly obtained by biopsy. Except if TLS analysis have been already performed by Biopathological platform at Bergonié Institute, presence or absence of TLS should be confirmed by central review based on FFPE tumor tissue sample (archived or newly obtained by biopsy for research purpose),
• Age ≥ 18 years,
• ECOG ≤ 1,
• Life expectancy \> 3 months,
• Patients must have measurable disease defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension as \> 10 mm with spiral CT scan.,
• Patient must comply with the collection of tumor biopsies and biomarkers study. Tumors must be accessible for biopsy,
• Adequate hematological, renal, metabolic and hepatic function
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization. Serum or urine pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication,
• Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for at least two months after discontinuation of treatment for women and four months for men.
• No prior or concurrent malignant disease diagnosed or treated in the last 3 years except for superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in \> 1 year,
• Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia and vitiligo of any grade and non-painful peripheral neuropathy grade ≤ 2) according to to NCI-CTCAE, version 5.0,
• Voluntarily signed and dated written informed consent prior to any study specific procedure,

You may not qualify if:

• Previous treatment with doxorubicin, daunorubicin, epirubicin, idarubicin and/or any other anthracyclines or anthracediones at the maximum cumulative dose or any approved or investigational treatment targeting PD1, PD-L1 or TGFB1,
• Known central nervous system malignancy (CNS),
• Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding,
• Participation to a study involving a medical or therapeutic intervention in the last 30 days,
• Previous enrolment in the present study,
• Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
• Known hypersensitivity to any involved study drug or any of its formulation components,
• Any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma,
• Individuals deprived of liberty or placed under legal guardianship,
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTcF) ≥ 470 msec, obtained from three consecutive ECGs,
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG,
• LVEF ≤ 50% per CTCAE v5 by MUGA or echocardiogram
• Any factors increasing the risk of QTc prolongation or arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years old or any concomitant medication known to prolong the QT interval,
• Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, uncontrolled hypertension, congestive heart failure NYHA Grade ≥2, ventricular arrhythmias requiring continuous therapy, supraventricular arrhythmias including atrial fibrillation, which are uncontrolled, haemorrhagic or thrombotic stroke, including transient ischaemic attacks, cerebral vascular accident/stroke or any other central nervous system bleeding

Sponsors & Collaborators

• Institut Bergonié: lead
• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (8)

Institut Bergonie

Bordeaux, 33000, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

NOT YET RECRUITING

Centre Léon Bérard

Lyon, 69000, France

RECRUITING

Institut Paoli Calmette

Marseille, 13000, France

NOT YET RECRUITING

Institut Curie

Paris, 75000, France

NOT YET RECRUITING

CHU Poitiers

Poitiers, 86000, France

RECRUITING

IUCT Oncopole

Toulouse, 31000, France

WITHDRAWN

Institut Gustave Roussy

Villejuif, 94805, France

WITHDRAWN

MeSH Terms

Conditions

Sarcoma; Tertiary Lymphoid Structures; Neoplasm Metastasis

Interventions

bintrafusp alfa protein, human; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Pathologic Processes

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Antoine ITALIANO, MD, PhD

CONTACT

+33556333333; a.italiano@bordeaux.unicancer.fr

Simone MATHOULIN-PELISSIER, MD, PhD

CONTACT

s.mathoulin@bordeaux.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: May 5, 2021
• Study Start: March 1, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 13, 2025

Record last verified: 2025-08

Locations

FR (8)