Clinical trial NCT02609984: Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
Official title: A Randomized, Open-Label, Phase 2 Trial of CMB305 (Sequentially Administered LV305 and G305) and Atezolizumab in Patients With Locally Advanced, Relapsed, or Metastatic Sarcoma Expressing NY-ESO-1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2015-11-20
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 36.1 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 36.1 months
Secondary outcomes:
measure: Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
timeFrame: Up to approximately 42 days
measure: Number of Participants Who Experienced At Least One Adverse Event (AE)
timeFrame: Up to approximately 36.1 months
measure: Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to approximately 24 months
measure: Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Month 3
measure: Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Month 6
measure: Time to Next Treatment (TTNT)
timeFrame: Up to approximately 36.1 months
measure: Distant Metastasis Free Survival (DMFS)
timeFrame: Up to approximately 36.1 months
measure: Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline
timeFrame: Baseline (Day 1)
measure: Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment
timeFrame: Up to approximately 24 months
measure: Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline
timeFrame: Baseline (Day 1)
measure: Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment
timeFrame: Up to approximately 24 months
Other outcomes:
measure: Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 36.1 months
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic of Jacksonville
state: Florida
city: Sandy Springs
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinburg School of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Lake Success
country: United States
facility: Monter Cancer Research
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Burlington
country: United States
facility: University of Vermont Cancer Center
state: Vermont
city: Seattle
country: United States
facility: Scca/Fhcrc
state: Washington
Study officials:
References:
citation: 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.