Neoadjuvant Chemotherapy and Retifanlimab in Patients With Selected Sarcomas (TORNADO)

NCT04968106 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: IB 2021-012021-001085-37
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of retifanlimab (INCMGA00012) in association with neoadjuvant chemotherapy

Conditions

Resectable Sarcoma

Keywords

sarcoma; neoadjuvant chemotherapy; mature tertiary lymphoid structures; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• Assessment of the antitumor activity of retifanlimab when prescribed in association with neoadjuvant chemotherapy (doxorubicin+ifosfamide)

  Antitumor activity will be assessed in terms of histological response based on surgical sample

  5 months after treatment onset

Secondary Outcomes (5)

• 1-year progression-free survival

  1 year

• 3-year progression-free survival

  3 years

• 1-year overall survival

  1 year

• 3-year overall survival

  3 years

• Safety profile independently for each arm: Common Terminology Criteria for Adverse event version 5

  Throughout the treatment period, an expected average of 6 months

Study Arms (2)

Standard Arm A: treatment by neoadjuvant chemotherapy

OTHER

Treatment by doxorubicin and ifosfamide followed by surgery

Drug: Doxorubicin; Drug: Ifosfamide

Experimental Arm B: treatement by neoadjuvant chemotherapy and retifanlimab

EXPERIMENTAL

Treatment by doxorubicin, ifosfamide and retifanlimab followed by surgery

Drug: Doxorubicin; Drug: Ifosfamide; Drug: INCMGA00012

Interventions

Doxorubicin DRUG

Doxorubicin will administered by intravenous infusion on day 1 every 3 weeks (75 mg/m²) up to 3 cycles

Experimental Arm B: treatement by neoadjuvant chemotherapy and retifanlimab; Standard Arm A: treatment by neoadjuvant chemotherapy

Ifosfamide DRUG

Ifosfamide will be administered by intravenous infusion over 3 days every 3 weeks (9 g/m²) up to 3 cycles

Experimental Arm B: treatement by neoadjuvant chemotherapy and retifanlimab; Standard Arm A: treatment by neoadjuvant chemotherapy

INCMGA00012 DRUG

Retifanlimab will be administered by intravenous infusion on day 1every 3 weeks (375 mg) up to 3 cycles

Also known as: Retifanlimab

Experimental Arm B: treatement by neoadjuvant chemotherapy and retifanlimab

Eligibility Criteria

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

You may qualify if:

• Patients with grade 2 or grade 3 soft-tissue sarcoma (limb, trunk wall, retroperitoneum) histologically confirmed and reviewed by the RRePS Network
• For TLS status determination: available archived FFPE tumor tissue sample.
• Presence of mature tertiary lymphoid structures. Except if presence of TLS have been already confirmed by Biopathological platform at Bergonié Institute, presence of TLS should be confirmed by central review based on FFPE tumor tissue sample (archived or newly obtained by biopsy for research purpose).
• Non-metastatic and resectable disease,
• At least one lesion that can be biopsied for research purpose,
• No prior treatment for the disease under study,
• Age ≥ 18 years,
• ECOG ≤ 1,
• Life expectancy \> 3 months,
• Patients must have measurable disease defined as per RECIST v1.1
• Adequate hematological, renal, metabolic and hepatic function
• Left ventricular ejection fraction ≥ 50% assessed by ECHO or MUGA within 6 months from study entry,
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry. .
• Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for one year after discontinuation of treatment for women and 4 months for men.
• No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, concomitant endometrial carcinoma stage IA grade 1, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,

You may not qualify if:

• Previous treatment for retroperitoneal sarcoma including surgery, chemotherapy or radiotherapy
• Previous treatments with doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines or anthracenediones at the maximum cumulative dose,
• Known hypersensitivity to any involved study drug or any of its formulation components,
• Has an active or ongoing infection requiring systemic therapy,
• Known central nervous system malignancy (CNS),
• Women who are pregnant or breast feeding,
• Has known active hepatitis B or hepatitis C,
• Has a known history of Human Immunodeficiency Virus (HIV),
• Previous enrolment in the present study,
• Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
• Has received a live attenuated vaccine or a live vaccine within 30 days prior to the first dose of trial treatment, Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction or stroke/transient ischemic attack within the 6 months prior to study entry.
• Uncontrolled angina within the 3 months prior to study entry.
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes, or poorly controlled atrial fibrillation).

Sponsors & Collaborators

• Institut Bergonié: lead
• Incyte Biosciences International Sàrl: collaborator

Study Sites (3)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Curie

Paris, France

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin; Ifosfamide

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; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Model Details: This is a multicenter, prospective, open-labeled, 2-arm, non-comparative randomized (1:1) phase II trial. Patients will be randomized between arm A (neodjuvant chemotherapy by doxorubicin + ifosfamide) and arm B (neodjuvant chemotherapy by doxorubicin + ifosfamide and retifanlimab) with one patient randomized in arm A for one patient randomized in arm B

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 20, 2021
• Study Start: December 7, 2022
• Primary Completion: August 6, 2025
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)