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

NCT04216953 | Completed Phase 1 DMC

• 1 other identifier: ET 19-036 COTESARC
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 6

Brief 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).

Conditions

Sarcoma,Soft Tissue

Keywords

MEK Inhibitor; PDL1 inhibitor

Outcome Measures

Primary Outcomes (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.

  16 weeks

Secondary Outcomes (3)

• Objective response rate

  at 8 weeks and 16 weeks

• Duration of response

  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.

• Progression-free survival

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

Study Arms (1)

Atezolizumab + Cobimetinib

EXPERIMENTAL

Atezolimumab : * 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.

Drug: Cobimetinib; Drug: Atezolizumab

Interventions

Cobimetinib DRUG

Adults: 20mg film coated tablet Paediatrics: i) 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

Also known as: GDC-0973

Atezolizumab + Cobimetinib

Atezolizumab DRUG

20-mL glass vial containing 1200 mg of atezolizumab.

Also known as: RO5541267

Atezolizumab + Cobimetinib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (6)

Institut de Cancérologie de l'Ouest

Angers, 49055, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital de la Timone

Marseille, 13385, France

Location

Institut Curie

Paris, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Sarcoma

Interventions

cobimetinib; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Nadège Corradini, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: January 3, 2020
• Study Start: February 12, 2020
• Primary Completion: December 1, 2024
• Study Completion: March 17, 2025
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

FR (6)