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

NCT02609984 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: IMDZ-C232V943A-002
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 18

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.

Conditions

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

Keywords

immunotherapy; CMB305; LV305; GLA-SE; atezolizumab; NY-ESO-1

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use immune-related response criteria (irRC) confirmation and unidimensional tumor measurements as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.

  Up to approximately 36.1 months

• Overall Survival (OS)

  OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data.

  Up to approximately 36.1 months

Secondary Outcomes (11)

• Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)

  Up to approximately 42 days

• Number of Participants Who Experienced At Least One Adverse Event (AE)

  Up to approximately 36.1 months

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

  Up to approximately 24 months

• Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Month 3

• Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Month 6

Other Outcomes (1)

• Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 36.1 months

Study Arms (2)

CMB305 (sequentially administered LV305 and G305)+Atezolizumab

EXPERIMENTAL

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.

Biological: CMB305; Biological: atezolizumab

Atezolizumab

ACTIVE COMPARATOR

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

Biological: atezolizumab

Interventions

CMB305 BIOLOGICAL

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

CMB305 (sequentially administered LV305 and G305)+Atezolizumab

atezolizumab BIOLOGICAL

IV Infusion

Also known as: TECENTRIQ®

Atezolizumab; CMB305 (sequentially administered LV305 and G305)+Atezolizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead
• Genentech, Inc.: collaborator

Study Sites (18)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic of Jacksonville

Jacksonville, Florida, 32224, United States

Location

Georgia Cancer Specialists

Sandy Springs, Georgia, 30342, United States

Location

Northwestern University Feinburg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 10029, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Monter Cancer Research

Lake Success, New York, 11042, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Fox Chase cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Vermont Cancer Center

Burlington, Vermont, 05405, United States

Location

Scca/Fhcrc

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 34260265 DERIVED

MeSH Terms

Conditions

Sarcoma; Liposarcoma, Myxoid; Sarcoma, Synovial; Liposarcoma

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 14, 2015
• First Posted: November 20, 2015
• Study Start: April 29, 2015
• Primary Completion: February 6, 2019
• Study Completion: February 6, 2019
• Last Updated: July 7, 2020
• Results First Posted: May 14, 2020

Record last verified: 2020-06

Locations

US (18)