Combination of Nivolumab Plus Relatlimab in Patients With Advanced or Metastatic Soft-tissue Sarcoma: a Proof-of-concept Randomized Phase II Study

NCT04095208 | Completed Phase 2 DMC

• 3 other identifiers: IB 2019-032019-002332-81CA224-085
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter study assessing the efficacy of nivolumab in association with relatlimab.

Conditions

Soft Tissue Sarcoma Adult; Advanced Cancer

Keywords

soft-tissue sarcoma; tertiary lymphoid structure; immunotherapy; oncology; metastatic

Outcome Measures

Primary Outcomes (1)

• Assessment of the antitumor activity of nivolumab in association with relatlimab independently for each arm

  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), based on RECIST 1.1

  6 months

Secondary Outcomes (11)

• Best overall response, independently for each arm

  throughout the treatment period, an expected average of 6 months

• 1-year progression-free survival, independently for each arm

  1 year

• 2-year progression-free survival, independently for each arm

  2 years

• 1-year overall survival, independently for each arm

  1 year

• 2-year overall survival, independently for each arm

  2 years

Study Arms (2)

Experimental: Randomized phase II trial - Arm A

EXPERIMENTAL

Combination of nivolumab and relatlimab.

Drug: Association of Nivolumab + Relatlimab

Experimental: Randomized phase II trial - Arm B

EXPERIMENTAL

Treatment by nivolumab alone.

Drug: Nivolumab

Interventions

Association of Nivolumab + Relatlimab DRUG

A treatment cycle consists of 4 weeks. Nivolumab will be administered as a 30-minutes intravenous infusion, on Days 1 and 15 of each cycle (every 2 weeks) - \[240 mg\]. Relatlimab will be administered as a 60-minutes intravenous infusion, on Days 1 and 15 of each cycle (every 2 weeks) - \[80 mg\].

Experimental: Randomized phase II trial - Arm A

Nivolumab DRUG

A treatment cycle consists of 4 weeks. Nivolumab will be administered as a 30-minutes intravenous infusion, on Days 1 and 15 of each cycle (every 2 weeks) - \[240 mg\].

Experimental: Randomized phase II trial - Arm B

Eligibility Criteria

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

You may qualify if:

• Histology: participant with soft tissue sarcoma histologically confirmed and reviewed by the RRePS Network as recommended by the French NCI (Inca),
• Presence of mature tertiary lymphoid structures (TLS). 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 (Formalin-Fixed Paraffin-Embedded) tumor tissue sample (archived or newly obtained by biopsy for research purpose). Note that the presence of TLS could be determined by central analysis if not available before,
• Deleted MSA5
• For research purpose, have provided tissue of a tumor lesion from \< 3 months old archival tissue sample (both frozen or FFPE) obtained on locally advanced disease, or metastasis, with no subsequent treatment since or presence of tumor lesion that can be biopsied,
• Advanced non resectable / metastatic disease,
• At least one tumor site that can be biopsied for research purpose,
• Previous treatment: no more than 2 previous lines of systemic therapy for advanced or metastatic disease
• Participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1,
• Life expectancy \> 3 months,
• No symptomatic central nervous system disease,
• No chronic use of glucocorticoids higher than 10 mg/day prednisone equivalent,
• Adequate hematological, renal, metabolic and hepatic function:
• Hemoglobin \> 9 g/dl (patients may have received prior red blood cell \[RBC\] transfusion, if clinically indicated); leucocytes ≥ 2 G/l, absolute neutrophil count (ANC) \> 1.5 G/l and platelet count \> 100 G/l, lymphocyte count \> 0.5 G/l

You may not qualify if:

• Previous treatment with an PD1/PDL1, LAG-3
• Previous enrolment in the present study,
• Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
• Women who are pregnant or breast feeding,
• Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
• Known hypersensitivity to any involved study drug or of its formulation components,
• Participation to a study involving a medical or therapeutic intervention in the last 30 days,
• Uncontrolled cardiac arrhythmia or hypertension, as per investigator discretion,
• 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).
• Corrected QT (QTc) prolongation \> 480 msec.
• History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled venous thrombus).
• Cardiovascular disease-related requirement for daily supplemental oxygen.

Sponsors & Collaborators

• Institut Bergonié: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Léon Bérard

Lyon, 69000, France

Location

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Nantes, 44805, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Sarcoma; Tertiary Lymphoid Structures; Neoplasms; Neoplasm Metastasis

Interventions

relatlimab; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: Parallel assignment

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 19, 2019
• Study Start: February 27, 2020
• Primary Completion: September 29, 2024
• Study Completion: March 29, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

FR (5)