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Sarcoma,Soft TissuePhase 1/2COTESARCNCT04216953

MEK Inhibitor and a PDL1 Inhibitor Patients With Locally Advanced and/or Metastatic Soft Tissue Sarcoma

A Phase 1/2 study testing Cobimetinib and Atezolizumab in people with Sarcoma,Soft Tissue, run by Centre Leon Berard at 6 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The proposed study conducted in adult and pediatric patients aims to evaluate the safety and clinical activity of atezolizumab + cobimetinib in advanced/metastatic soft tissue sarcomas (up to 80 patients). Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Sarcoma,Soft Tissue
What is being tested?
Cobimetinib and Atezolizumab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
229 participants
Where
6 sitesFrance
Study dates
12 Feb 2020to 17 Mar 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • I1. Male or female patients aged of at least :
  • 12 years on day of signing informed consent.
  • I2. Histologically-confirmed diagnosis of soft tissue sarcomas, confirmed by a pathologist from RRePS Network, among the 2 cohorts:
  • Rhabdomyosarcomas (RMS).
  • Malign Peripheral Nerve Sheath Tumors (MPNST). I3. Availability of a representative formalin-fixed paraffin-embedded (FFPE) primary and/or metastatic tumor tissue with an associated pathology report for molecular prescreening i.e. either an archival block or a dedicated freshly collected de novo tumor biopsy.
  • I4. Documented MAPK pathway status and known Tumor Mutational Burden (TMB) before C1D1.
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  • I5. Previous treatment with anthracycline-based chemotherapy (in the neoadjuvant, adjuvant or metastatic setting). Note: this criteria not mandatory for rhabdomyosarcoma.
  • I6. Previous treatment by at least one line of chemotherapy in the advanced/metastatic setting before C1D1.
  • I7. Documented radiological disease progression as per RECIST V1.1 before C1D1.
  • I8. At least one measurable lesion according to RECIST v1.1 before C1D1.
  • I9. Mandatory for adult patients only - Presence of at least one tumor lesion visible by medical imaging and accessible to repeatable percutaneous sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of 4 cores using a 16-gauge diameter needle or larger.
  • I10. Performance status:
  • Karnofsky performance status for pediatric patients ≥12 years of age ≥ 70%;
  • PS ECOG for adult patients: 0 or 1.
  • I11. Life expectancy of at least 16 weeks.
  • I12. Demonstrate adequate organ function based on screening laboratory tests performed within 7 days prior C1D1: Absolute neutrophil count ≥1.5 10 exp. 9/L; Platelets ≥100 10 exp. 9/L; Hemoglobin ≥9 g/dL; Serum creatinine OR Creatinine clearance according to CKD-EPI for adult and C-KID formula for pediatric patients ≤1.5 X ULN OR ≥ 30 mL/min/1.73m2 for patient with creatinine levels > 1.5 ULN; Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN; ASAT and ALAT and ALP ≤ 3 X ULN; INR and Activated Partial Thromboplastin Time (aPTT)≤1.5 X ULN; Troponin T or I negative (< ULN).
  • I13. Resolution (i.e. ≤ Grade 1 with the exception of alopecia all grades and Grade 2 for neuropathy, lab values presented in criteria I12.) of any toxicities related to previous anti-cancer treatment.
  • I14. Women patient of child-bearing potential must have a negative serum pregnancy test before C1D1 and must agree to use effective forms of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drugs.
  • I15. Sexually active and fertile men must agree to use contraceptive measures up to 5 months after the last study drugs.
  • I16. Written informed consent from patient, parents if applicable/legal representative, before any study-specific screening procedures, and willingness to comply to study visits and procedures.
  • I17. Patients must be covered by a medical insurance.

Who cannot join

  • NI1. Soft tissue sarcoma disease considered curable with surgery or radiotherapy.
  • NI2. Prior treatment with cobimetinib or other MEK inhibitors. NI3. Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapeutic antibodies.
  • NI4. Patients with history of severe allergic or other hypersensitivity reactions to:
  • Chimeric or humanized antibodies or fusion proteins,
  • Biopharmaceuticals produced in Chinese hamster ovary cells, or
  • Any component of the atezolizumab formulation.
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  • Any component of Cobimetinib formulation.
  • NI5. History of malabsorption syndrome or other condition that would interfere with the absorption of oral medications.
  • NI6. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
  • Note: Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
  • Measurable disease, per RECIST v1.1, must be present outside the CNS.
  • No history of intracranial hemorrhage or spinal cord hemorrhage.
  • Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
  • No stereotactic radiotherapy within 7 days prior to initiation of study treatments, whole-brain radiotherapy within 14 days prior to initiation of study treatment, neurosurgical resection within 28 days prior to initiation of study treatments.
  • No evidence of interim progression between completion of CNS-directed therapy and initiation of study treatments.
  • No ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
  • NI7. History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration.
  • NI8. Left ventricular ejection fraction (LVEF) < institutional lower limit of normal (according to age) or < 50%.
  • NI9. History of congenital long QT syndrome or corrected QT interval (QTc) > 450 ms.
  • NI10. Patients using, or requirement to use while on the study, or not respecting the minimal wash-out period of medications listed below:
  • Any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, or immunotherapy: 2 weeks; any investigational agents: 4 weeks; Radiotherapy: 3 weeks; major surgical procedure, open biopsy, or significant traumatic injury: 4 weeks; abdominal surgery, abdominal interventions or significant abdominal traumatic injury : 60 days; live vaccines : 4 weeks; systemic immunostimulatory agents, including but not limited to IFN-α, IFN-γ, or IL-2 : 4 weeks; immunosuppressive medications with the exceptions of intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid: 2 weeks; P-gp inhibitors : None; Strong or moderate inhibitors of CYP3A4 : None; Strong CYP3A4 inducers: None; oral or IV antibiotics : 2 weeks.
  • NI11. Patients with a malignancy other than STS within 5 years prior to C1D1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
  • NI12. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
  • patients with a history of autoimmune-related hypothyroidism who are on stable thyroid replacement hormone therapy,
  • patients with controlled Type 1 diabetes mellitus,
  • patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are eligible provided that they meet the following conditions:
  • rash must cover less than 10% of body surface area (BSA).
  • disease is well controlled at baseline and only requiring low potency topical steroids.
  • no acute exacerbations of underlying condition within the previous 12 months requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids.
  • NI13. Patients with HIV, active B or C hepatitis infection, or any other active infection.
  • Active hepatitis C i.e. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at screening.
  • NI14. Patients with active tuberculosis. NI15. Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past.
  • NI16. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
  • NI17. Patients with a high-risk of hemorrhage or history of coagulopathy. NI18. Pregnant or breastfeeding women. N19. Patients with a history of immune-mediated pericardial disorder (including pericarditis) related to immune-stimulatory anticancer agents

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

France6 sites

  • Institut de Cancérologie de l'Ouest

    Angers, 49055

  • Centre Oscar Lambret

    Lille, 59020

  • Centre Léon Bérard

    Lyon, 69008

  • Hôpital de la Timone

    Marseille, 13385

  • Institut Curie

    Paris

  • Institut Gustave Roussy

    Villejuif, 94800

Other trials in France

About this study

Official title: A Multicentre, Open-label, Phase I-II Study Evaluating the Combination of a MEK Inhibitor and a PDL1 Inhibitor in Pediatric and Adult Patients With Locally Advanced and/or Metastatic Soft Tissue Sarcoma.

The proposed study conducted in adult and pediatric patients aims to evaluate the safety and clinical activity of atezolizumab + cobimetinib in advanced/metastatic soft tissue sarcomas (up to 80 patients).

Read the detailed description

The hypothesis of the proposed combination is as follows: cobimetinib via MEK1/2 inhibition could modify the tumor microenvironment and improve the response of T cells against tumor cells. Therefore, the addition of cobimetinib to atezolizumab may improve immune recognition and result in improved anti-tumour activity.

The combination of cobimetinib and atezolizumab showed clinical activity in a Phase I trial in patients with metastatic colorectal cancer (Atezolizumab 840 mg every 2 weeks and Cobimetinib 60 mg/d) with a disease control rate of 31%. Atezolizumab and cobimetinib are currently being tested in pediatrics in the iMatrix clinical trial with no major safety concerns to date.

A molecular screening step is mandatory for all patients enrolled in this trial in order to document MAPK pathway status and Tumor Mutational Burden (TMB) using FoundationOne test (FOne Heme).

Being tested
Cobimetinib, Atezolizumab
Keywords
MEK Inhibitor, PDL1 inhibitor
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobimetinibDrug

    Also called GDC-0973

    Adults: 20mg film coated tablet

    Paediatrics:

    1. powder for oral suspension containing 250mg of cobimetinib ii) for pediatric patients ≥12 years-old and with a BW ≥60kg : 20mg film coated tablet same as adults

  • AtezolizumabDrug

    Also called RO5541267

    20-mL glass vial containing 1200 mg of atezolizumab.

Study groups in NCT04216953
Study groupRoleWhat they receive
Atezolizumab + CobimetinibExperimentalAtezolimumab : * Adult Patient and patients ≥12 years-old with a BW ≥60kg: 840mg, Q2W * Pediatric Patient including patients ≥12 years-old with a BW <60kg: 15mg/kg, Q2W with a maximum of 840mg. Cobimetinib : * Pediatric patients ≥ 12 and a BW < 60kg:1mg/kg. Pediatric patients ≥ 12 and with a BW ≥ 60kg: 60mg/d. * Adult Patients: 60mg/d D1 to D21 over a 28-day cycle.
Receives: Drug: Cobimetinib; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase II part

    The Progression Free rate after 16 weeks of treatment is defined as the rate of patients with a complete response or a partial response or a stable disease as per RECIST V1.1.

    Measured: 16 weeks

Secondary outcomes (3)

  1. Objective response rate

    The objective response rate at 8 (16) weeks is defined as the proportion of patients with a complete response or a partial response after 8 (16) weeks of treatment.

    Measured: at 8 weeks and 16 weeks

  2. Duration of response

    Duration of response is defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the date of documented progression or death in the absence of disease progression.

    Measured: Time interval from the date of first occurrence of a documented objective response until the date of documented progression or death in the absence of disease progression up to 3 month.

  3. Progression-free survival

    Progression-free survival (PFS) is defined as the time from the first day of study treatment to the date of the first documented tumor progression or death due to any cause, whichever occurs first.

    Measured: Time from the first day of study treatment to the date of the first documented tumor progression or death up to 3 month.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2020
  2. Study start12 Feb 2020
  3. Primary completion1 Dec 2024
  4. Study completion17 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
229 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04216953
Sponsor's protocol ID
ET 19-036 COTESARC
Acronym
COTESARC
Status last verified
Apr 2026
First submitted
18 Dec 2019
Last updated
23 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cobimetinib and Atezolizumab in people with Sarcoma,Soft Tissue, run by Centre Leon Berard at 6 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase II part (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04216953.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.

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