Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)

NCT ID: NCT02609984

Last Updated: 2020-07-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-29
• Study Completion Date: 2019-02-06

Brief Summary

This is an open-label Phase 2 randomized study that will examine the use of the study agents, CMB305 (sequentially administered LV305 which is a dendritic cell-targeting viral vector expressing the New York Esophageal Squamous Cell Carcinoma 1 gene [NY-ESO-1] and G305 which is a NY-ESO-1 recombinant protein plus glucopyranosyl lipid adjuvant-stable emulsion [GLA-SE]) in combination with atezolizumab or atezolizumab alone, in participants with locally advanced, relapsed or metastatic sarcoma (synovial or myxoid/round cell liposarcoma) expressing the NY-ESO-1 protein.

There is no formal primary hypothesis for this study.

Detailed Description

This study is designed to investigate and examine the time to progression and overall survival for CMB305 in combination with atezolizumab or atezolizumab alone in the treatment of participants with sarcoma expressing NY-ESO-1 protein.

Conditions

Sarcoma; Myxoid/Round Cell Liposarcoma; Synovial Sarcoma; Metastatic Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Locally Advanced Sarcoma; Liposarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CMB305 (sequentially administered LV305 and G305)+Atezolizumab

Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered intradermally (ID) on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered intramuscularly (IM) and LV305. LV305 was administered at a dose of 1×10\^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.

Group Type: EXPERIMENTAL

CMB305

Intervention Type: BIOLOGICAL

A combination of LV305 administered intradermally (ID) and G305 administered intramuscularly (IM)

atezolizumab

Intervention Type: BIOLOGICAL

IV Infusion

Atezolizumab

Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.

Group Type: ACTIVE_COMPARATOR

atezolizumab

Intervention Type: BIOLOGICAL

IV Infusion

Interventions

CMB305

A combination of LV305 administered intradermally (ID) and G305 administered intramuscularly (IM)

Intervention Type: BIOLOGICAL

atezolizumab

IV Infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

TECENTRIQ®

Eligibility Criteria

Inclusion Criteria

• Locally advanced, relapsed, or metastatic sarcoma with measurable tumor burden following therapy, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); the total of all lesions must be ≤12 cm (for synovial sarcoma) or ≤15 cm (for myxoid/round cell liposarcoma [MRCL])
• Tumor histology consistent with synovial sarcoma or MRCL
• Tumor specimen positive for NY-ESO-1 expression by immunohistochemistry (IHC)
• Inadequate response, relapse, and/or unacceptable toxicity with ≥1 prior systemic, surgical, or radiation cancer therapies
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria

• Investigational therapy within 4 weeks prior to CMB305 dosing
• Prior administration of other NY-ESO-1-targeting immunotherapeutics
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-programmed cell death receptor 1 (PD-1), and anti-programmed cell death ligand (PD-L1) therapeutic antibodies, or any other antibody or drug targeting T-cell costimulation
• Treatment with systemic immunostimulatory agents (including but not limited to interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first dose
• Significant immunosuppression
• Other cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors within 3 weeks prior to the first scheduled dosing
• 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-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• History of other cancer within 3 years
• Evidence of active tuberculosis or recent (<1 week prior to first scheduled dosing) clinically significant infection requiring systemic therapy
• Evidence of active hepatitis B (HepB), hepatitis C (HepC), or Human Immunodeficiency Virus (HIV) infection
• Known active or untreated central nervous system (CNS) metastases
• Pregnant, planning to become pregnant within 6 months of treatment, or nursing
• Known allergy(ies) to any component of CMB305, atezolizumab, or severe allergic reactions to monoclonal antibodies, fusion proteins, or Chinese hamster ovary (CHO) cell products

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford University Medical Center

Palo Alto, California, United States

Sarcoma Oncology Research Center

Santa Monica, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Mayo Clinic of Jacksonville

Jacksonville, Florida, United States

Georgia Cancer Specialists

Sandy Springs, Georgia, United States

Northwestern University Feinburg School of Medicine

Chicago, Illinois, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

Monter Cancer Research

Lake Success, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Duke Cancer Institute

Durham, North Carolina, United States

Fox Chase cancer Center

Philadelphia, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Vermont Cancer Center

Burlington, Vermont, United States

Scca/Fhcrc

Seattle, Washington, United States

Countries

United States

References

Chawla SP, Van Tine BA, Pollack SM, Ganjoo KN, Elias AD, Riedel RF, Attia S, Choy E, Okuno SH, Agulnik M, von Mehren M, Livingston MB, Keedy VL, Verschraegen CF, Philip T, Bohac GC, Yurasov S, Yakovich A, Lu H, Chen M, Maki RG. Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1. J Clin Oncol. 2022 Apr 20;40(12):1291-1300. doi: 10.1200/JCO.20.03452. Epub 2021 Jul 14.

Reference Type: DERIVED

PMID: 34260265 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

V943A-002

Identifier Type: OTHER

Identifier Source: secondary_id

IMDZ-C232

Identifier Type: OTHER

Identifier Source: secondary_id

IMDZ-C232

Identifier Type: -

Identifier Source: org_study_id