Clinical trial NCT03989362: Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Subjects With NSCLC or Urothelial Cancer
Official title: Phase 2 Multicenter Trial of ICOS Agonist Monoclonal Antibody (mAb) Vopratelimab (JTX -2011) and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Adult Subjects With Non-small Cell Lung Cancer or Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: ICOS
ICOS agonist monoclonal antibody
JTX-2011
Vopratelimab
Anti-CTLA-4
Ipilimumab
EMERGE
Immunotherapy
Immuno-Oncology
Cancer
Non-small Cell Lung Cancer
Urothelial Cancer
Lead sponsor: Jounce Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-18
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: JTX-2011-201 is a Phase 2, open label clinical study of vopratelimab (JTX-2011) and ipilimumab in adult subjects with non-small cell lung cancer (NSCLC) or urothelial cancer to evaluate safety and efficacy.

Detailed description: Vopratelimab (JTX-2011) is an agonist monoclonal antibody that specifically binds to the Inducible CO-Stimulator of T cells (ICOS) to generate an anti-tumor immune response. This is a Phase 2, open label study to evaluate the safety and efficacy of vopratelimab in combination with ipilimumab in adult subjects with advanced and/or refractory non-small cell lung cancer and urothelial cancer.

Eligibility criteria: Inclusion Criteria:

1. Willing and able to participate and comply with all trial requirements and able to provide signed and dated informed consent prior to initiation of any trial procedures
2. Male or female ≥ 18 years of age
3. Locally advanced, inoperable or metastatic NSCLC or urothelial cancer, with evaluable or measurable disease, according to RECIST v1.1, with at least one measurable lesion
4. Prior treatment with a PD-1/PD -L1 inhibitor for at least 3 months
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Predicted life expectancy ≥ 3 months
7. Have laboratory values in accordance with the study protocol
8. If medical history of the following, case should be reviewed with the Medical Monitor: prior biliary tract disorders (as based on Hepatobiliary system organ class high level terms of obstructive bile duct disorders, hepatic vascular disorders, structural and other bile duct disorders) or portal hypertension and/or hepatic vascular disorders
9. Women of child-bearing potential (WOCBP): negative serum pregnancy test within 72 hours prior to planned C1D1 and a negative urine pregnancy test on C1D1 and any subsequent study drug administration day
10. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration. Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly. For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on the contraceptive should be addressed.

Exclusion Criteria:

1. Concurrent anticancer treatment (either approved or investigational, excluding radiation therapy)
2. Prior anticancer therapies within the timeframes specified below, or ongoing toxicity from prior therapy \> Grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Exceptions include \> Grade 1 toxicities that, in the opinion of the Investigator, should not exclude the subject (e.g., alopecia) and are approved by the Medical Monitor:

   1. Biologic therapy, including immunotherapy, within 21 days prior to C1D1
   2. Chemotherapy within 21 days (42 days for mitomycin or nitrosoureas) prior to C1D1
   3. Anti-CTLA-4 or anti-ICOS therapy at any time
   4. Chimeric antigen receptor T-cell therapy at any time
   5. Organ transplantation, including allogeneic or autologous stem-cell transplantation, at any time
3. Major surgery (excluding minor procedures, e.g., placement of vascular access, biopsy, etc.) within 4 weeks prior to C1D1
4. Live vaccines within 30 days prior to C1D1 (inactivated vaccines are allowed; seasonal vaccines should be up to date prior to C1D1)
5. History of immune-related adverse events (irAEs) leading to treatment discontinuation. Subjects who discontinued prior immunotherapies for irAEs that are well controlled with appropriate treatment may be enrolled if approved by the Medical Monitor
6. Any active disease, including primary or acquired immunodeficiency, requiring systemic immunosuppressive therapy equivalent to ≥10 mg prednisone per day within 7 days prior to C1D1. Exception: inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease as well as a one-time dose of immunosuppressive agents used prophylactically for contrast allergies
7. Known severe intolerance to or life-threatening hypersensitivity reactions to humanized monoclonal antibodies or intravenous immunoglobulin preparations; history of anaphylaxis; or known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
8. Brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation
9. Prior whole brain radiation
10. Concurrent second malignancy at other sites that requires treatment or, in the judgment of the Investigator, may require treatment within the next year. Concurrent malignancies that do not require treatment and are clinically stable are allowed. Prior malignancies are allowed as long as the subject is not receiving specific treatment other than hormonal therapy and, in the judgment of the Investigator, is unlikely to have a recurrence
11. Active and clinically relevant bacterial, fungal, or viral infection, including known Hepatitis A, B, or C or human immunodeficiency virus (HIV) (testing not required)
12. Women who are pregnant or breastfeeding
13. History of symptomatic cardiac disease that is unresponsive to surgical or medical management
14. Any medical or social condition that, in the opinion of the Investigator, might place a subject at increased risk, affect compliance, or confound safety or other clinical trial data interpretation.

Primary outcomes:
measure: % subjects with overall response (OR)
timeFrame: 34 months
Secondary outcomes:
measure: % subjects with adverse events (AEs)
timeFrame: 34 months
measure: % subjects with serious adverse events (SAEs)
timeFrame: 34 months
measure: % subjects with clinically significant change from baseline in clinical laboratory tests
timeFrame: 34 months
measure: % subjects with anti-drug antibodies (ADA) to treatment
timeFrame: 34 months
measure: % of subjects with neutralizing antibodies (NAb) to treatment
timeFrame: 34 months
measure: % of subjects with clinically significant changes in electrocardiogram (ECG) measurements
timeFrame: 34 months
measure: Percent change in target lesions from baseline
timeFrame: 34 months
measure: Apparent volume of distribution during specific time points
timeFrame: 34 months
measure: Median duration of response (DOR)
timeFrame: 34 months
measure: Disease control rate (DCR)
timeFrame: 34 months
measure: Landmark progression free survival (PFS)
timeFrame: 34 months
measure: Median PFS
timeFrame: 34 months
measure: Median overall survival (OS)
timeFrame: 34 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California Medical Center
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Sarasota
country: United States
facility: Florida Cancer Specialists Sarasota Cattlemen
state: Florida
city: Baltimore
country: United States
facility: University of Maryland - Marlene and Stewart Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Clinton
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network Research Institute
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of The Texas Health Science Center at San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Toronto
country: Canada
facility: University Health Network - Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: The Research Institute of the McGill University Health
state: Quebec
city: Québec
country: Canada
facility: University Institute of Cardiology and Respirology of Quebec
Study officials:
affiliation: Jounce Therapeutics, Inc.
name: Ellen Hooper, MD
role: STUDY_DIRECTOR
References: