Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Subjects With NSCLC or Urothelial Cancer (EMERGE)

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Ipilimumab; Drug: Vopratelimab

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G5
    • University Institute of Cardiology and Respirology of Quebec
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network - Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • The Research Institute of the McGill University Health
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California Medical Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health Services
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists Sarasota Cattlemen
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland - Marlene and Stewart Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Research Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • University of The Texas Health Science Center at San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University Of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM1; Phase 2 study of vopratelimab by intravenous (IV) infusion administered in combination with ipilimumab by IV infusion in NSCLC	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: LT1; Phase 2 study of vopratelimab by IV infusion administered in combination with ipilimumab by IV infusion in NSCLC	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: UM1; Phase 2 study of vopratelimab by IV infusion administered in combination with ipilimumab by IV infusion in urothelial cancer	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: UT1; Phase 2 study of vopratelimab by IV infusion administered in combination with ipilimumab by IV infusion in urothelial cancer	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: LM2; Phase 2 study of vopratelimab by intravenous (IV) infusion in administered in sequence with ipilimumab by IV infusion in NSCLC	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: LT2; Phase 2 study of vopratelimab by intravenous (IV) infusion in administered in sequence with ipilimumab by IV infusion in NSCLC	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: UM2; Phase 2 study of vopratelimab by intravenous (IV) infusion in administered in sequence with ipilimumab by IV infusion in urothelial cancer	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011
Experimental: UT2; Phase 2 study of vopratelimab by intravenous (IV) infusion in administered in sequence with ipilimumab by IV infusion in urothelial cancer	Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Vopratelimab; Specified dose on specified days; Other Names: JTX-2011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
% subjects with overall response (OR)	34 months

Secondary Outcome Measures

Outcome Measure	Time Frame
% subjects with adverse events (AEs)	34 months
% subjects with serious adverse events (SAEs)	34 months
% subjects with clinically significant change from baseline in clinical laboratory tests	34 months
% subjects with anti-drug antibodies (ADA) to treatment	34 months
% of subjects with neutralizing antibodies (NAb) to treatment	34 months
% of subjects with clinically significant changes in electrocardiogram (ECG) measurements	34 months
Percent change in target lesions from baseline	34 months
Apparent volume of distribution during specific time points	34 months
Median duration of response (DOR)	34 months
Disease control rate (DCR)	34 months
Landmark progression free survival (PFS)	34 months
Median PFS	34 months
Median overall survival (OS)	34 months

Collaborators and Investigators

• Sponsor: Jounce Therapeutics, Inc.
• Investigators: Study Director: Ellen Hooper, MD, Jounce Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): March 15, 2022
• Study Completion (Actual): March 15, 2022

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 14, 2019
• First Posted (Actual): June 18, 2019

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; Immunotherapy; Ipilimumab; Non-small Cell Lung Cancer; Urothelial Cancer; ICOS; ICOS agonist monoclonal antibody; JTX-2011; Anti-CTLA-4; Immuno-Oncology; Vopratelimab; EMERGE
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: JTX-2011-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No