Combination of Pembrolizumab and Cabozantinib in Patients With Advanced Sarcomas

NCT05182164 | Recruiting Phase 2 DMC

• 1 other identifier: IB2020-02
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 10

Brief Summary

Phase II trial with three independent strata to independently assess the effects of the association of pembrolizumab and cabozantinib in advanced sarcomas.

Conditions

Soft Tissue Sarcoma Adult; Advanced Soft-tissue Sarcoma; Ewing Sarcoma; Osteosarcoma; Undifferentiated Pleomorphic Sarcoma

Keywords

soft-tissue sarcoma; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• Assessment of the efficacy of pembrolizumab and cabozantinib (independently for each stratum)

  Efficacy will be assessed in terms of non-progression rate at 6 months and is defined as the proportion of patients with complete response (CR), or partial response (PR), or stable disease (SD) at 6 months from the start of the treatment, based on RECIST 1.1 criteria.

  6 months

Secondary Outcomes (9)

• Best overall response, independently for each stratum

  Throughout the treatment period, an expected average of 6 months

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

  1 year

• 1-year overall survival, independently for each stratum

  1 year

• Safety profile, independently for each stratum: Common Terminology Criteria for Adverse Events version 5

  Throughout the treatment period, an expected average of 6 months

• 6-months non-progression rate according to iRECIST

  6 months

Study Arms (3)

Stratum 1: advanced undifferentiated pleomorphic sarcoma

EXPERIMENTAL

Patients with advanced undifferentiated pleomorphic sarcoma will be treated by the combination of pembrolizumab + cabozantinib

Drug: Association of pembrolizumab + cabozantinib

Stratum 2: advanced osteosarcoma

EXPERIMENTAL

Patients with advanced osteosarcoma will be treated by the combination of pembrolizumab + cabozantinib

Drug: Association of pembrolizumab + cabozantinib

Stratum 3: advanced Ewing sarcoma

EXPERIMENTAL

Patients with advanced Ewing sarcoma will be treated by the combination of pembrolizumab + cabozantinib

Drug: Association of pembrolizumab + cabozantinib

Interventions

Association of pembrolizumab + cabozantinib DRUG

A treatment cycle consists of 3 weeks. Pembrolizumab will be administered intraveinously on day 1 every 3 weeks (200 mg). Cabozantinib will be administered per os, once daily (40 mg), and given on a continuous basis.

Stratum 1: advanced undifferentiated pleomorphic sarcoma; Stratum 2: advanced osteosarcoma; Stratum 3: advanced Ewing sarcoma

Eligibility Criteria

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

You may qualify if:

• Histology: undifferentiated pleomorphic sarcoma (stratum 1), bone osteosarcoma (stratum 2), bone or extraskeletal or Ewing sarcoma (stratum 3),
• Advanced non resectable / metastatic disease,
• Recurrent disease or progression after standard therapy,
• Documented progression according to RECIST criteria.
• Have provided tissue of a tumor lesion from \< 3 months old archival tissue sample obtained on locally advanced disease, or metastatis with no subsequent treatment since or from a newly obtained core or excisional biopsy,
• No more of three previous lines of systemic therapy for advanced disease,
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group ≤ 1,
• Measurable disease according to RECIST v1.1 outside any previously irradiated field. At least one site of disease must be uni-dimensionally ≥ 10 mm,
• Life expectancy \> 3 months,
• 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,
• No symptomatic central nervous system disease,
• No chronic use of glucocorticoids.
• Adequate hematological, renal, metabolic and hepatic function,
• No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,

You may not qualify if:

• Previous treatment with Pembrolizumab or Cabozantinib,
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumabor any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways),
• Evidence of progressive or symptomatic central nervous system or leptomeningeal metastases,
• Men or women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding, men or women who are planning to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment,
• Participation to a study involving a medical or therapeutic intervention in the last 21 days,
• Previous enrolment in the present study,
• Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
• Patient unable to swallow,
• Known hypersensitivity to any involved study drug or of its formulation components,
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy is not considered a form of systemic treatment and is allowed.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment,
• History of idiopathic pulmonary fibrosis, history of non-infectious pneumonitis that required steroids, current pneumonitis/interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted,
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
• Has a known history of HIV infection and/or of active TB (Bacillus Tuberculosis),
• Treatment with anticoagulants such as anti-Vitamin K, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel),

Sponsors & Collaborators

• Institut Bergonié: lead
• Ipsen: collaborator
• MSD France: collaborator

Study Sites (10)

Institut Bergonie

Bordeaux, 33076, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

NOT YET RECRUITING

Centre Leon Berard

Lyon, 69008, France

NOT YET RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

Hôpital La Timone

Marseille, 13385, France

RECRUITING

Institut Curie

Paris, 75248, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, 44805, France

RECRUITING

IUCT Oncopole

Toulouse, 31059, France

NOT YET RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing; Osteosarcoma; Histiocytoma, Malignant Fibrous; Sarcoma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Histiocytoma; Neoplasms, Fibrous Tissue

Central Study Contacts

Maud TOULMONDE, MD

CONTACT

+33556333333; m.toulmonde@bordeaux.unicancer.fr

Simone MATHOULIN-PELISSIER, MD, PhD

CONTACT

s.mathoulin@bordeaux.unicancer.fr

Study Design

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

Model Details: 3 independent sigle-arm, multicenter, phase II trials, based on 2-stage Simon's optimal design

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 10, 2022
• Study Start: April 25, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Locations

FR (10)