ACTIVE_NOT_RECRUITING

A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)

Conditions

Neoplasms TSR-022 Nivolumab Advanced solid tumors Metastatic solid tumors Immunotherapy Colorectal cancer Non-small cell lung cancer Melanoma TSR-033 TSR-042 Hepatocellular carcinoma cancer Docetaxel

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a first-in-human study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022. The study will be conducted in 2 parts with Part 1 consisting of dose escalation and Part 2 dose expansion. Part 1 will determine the recommended Phase 2 dose (RP2D) of TSR-022 and Part 2 will evaluate the antitumor activity of TSR-022 in combination with TSR-042 or docetaxel and as monotherapy.

Official Title

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)

Quick Facts

Study Start:2016-07-08

Study Completion:2027-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT02817633

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	* History of Grade greater than or equal to (\>=)3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities. * Participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. * Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the Medical Monitor. * Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy. * Participant is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment. * Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. * A participant with negative (as determined by Central Testing Lab) or unevaluable TIM-3 expression from tissue obtained prior to study entry will not be eligible for the study. * Participant has received prior therapy as defined below: * Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE. * Prior treatment with an anti-lymphocyte activation gene (LAG)-3 or anti-TIM-3. * Radiologic or clinical progression \<= 8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody. * Participants with known epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) translocation, or receptor tyrosine kinase (ROS1) mutation. * Participant has received a vaccine other than a vaccine against severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) infection ("Coronavirus Disease 2019" \[COVID-19\]) within 7 days of planned start of study therapy. The use of all COVID-19 vaccines is allowed, with the exception of COVID-19 vaccines using the recombinant adenoviral vector platform within 30 days of planned start of study therapy. If a COVID-19 vaccine using this platform is to be administered within 30 days of planned start of study therapy, this must first be discussed with and approved by the Sponsor's Medical Monitor. * Participant has been previously treated with an anti PD 1, anti PD L1, or anti PD L2 agent that resulted in permanent discontinuation due to an AE * Participant has been previously treated with an anti TIM-3 or anti cytotoxic T lymphocyte-associated protein 4 (CTLA 4) agent or docetaxel. * Participant has a documented sensitizing EGFR, ALK, or ROS-1 mutation. Participants whose tumors have not been tested for these driver mutations and therefore who have unknown driver mutation status are not eligible. Participants with squamous histology do not need to be tested for these driver mutations. * Participant had radiological or clinical disease progression (that is \[ie,\] worsening performance status, clinical symptoms, and laboratory data) \<=8 weeks after initiation of prior anti PD 1 or anti-PD-L1 antibody. The clinical disease progression should have been confirmed by a subsequent radiological scan. * Participant has received radiation to the lung that is \>30 Gray (Gy) within 6 months prior to the first dose of study treatment. * Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment. * Participant has an additional malignancy or a history of prior malignancy, with the exception of adequately treated basal or squamous skin cancer, cervical carcinoma in situ, or bladder carcinoma in situ without evidence of disease, or had a malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy. * Participant has known new or progressive brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiologically stable central nervous system disease may participate, provided they are neurologically stable for at least 4 weeks before study entry and are off corticosteroids within 3 days prior to the first dose of study treatment. * Participant has tested positive for the following at Screening or within 3 months before the first dose of study treatment: * Presence of hepatitis B surface antigen. * Presence of hepatitis C antibody in the absence of an Ribonucleic acid (RNA) test for hepatitis C virus. * Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2 antibodies). * Participant has active autoimmune disease that required systemic treatment in the past 2 years, is immunocompromised in the opinion of the Investigator, or is receiving systemic immunosuppressive treatment. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy of prednisone, or equivalent, for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Participant has received systemic steroid therapy within 3 days prior to the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed. * Participant has current interstitial lung disease, current pneumonitis, or a history of pneumonitis that required the use of glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary. * Participant does not meet requirements per local prescribing guidelines for receiving treatment with docetaxel, including severe hypersensitivity reactions to drugs formulated with polysorbate 80. * Participant has received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half life of the most recent therapy prior to study Day 1, whichever is shorter. * Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC * Participant must not have had major surgery \<= 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects * Participants must not have received investigational therapy \<= 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior to initiating protocol therapy. * Active or untreated central nervous system (CNS) and leptomeningeal metastases * Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3 * Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components or excipients. * Participants with active malignancy (other than HCC) or a prior malignancy within the past 2 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible * Participant must not have serious, uncontrolled medical disorder, or nonmalignant systemic disease as determined by the treating physician. Examples include, but are not limited to uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome. * Has a history or evidence of cardiac abnormalities within the 6 months prior to enrollment, including: * Serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second-degree (Type II) or third-degree atrioventricular (AV) block. * Cardiomyopathy, myocarditis, myocardial infarction, acute coronary syndromes (including angina pectoris), coronary angioplasty, stenting, or bypass grafting. * Congestive heart failure \[New York Heart Association (NYHA) Class III or IV\] * Symptomatic pericarditis * Known history of HIV infection * Active tuberculosis infection or other microbial infection or any active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy. * Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (. i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchial asthma, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis * History of organ transplantation including allogeneic bone marrow transplantation * Participant has a diagnosis of immunodeficiency or has been receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy. * Participant has received a live vaccine within 7 days of initiating protocol therapy. Seasonal flu vaccines that do not contain live virus and COVID 19 vaccines are permitted. * Psychiatric illness/social situations that would limit compliance with study requirements * Pregnant, lactating, breastfeeding, or intending to become pregnant during the study and for 150 days after the study

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

* History of Grade greater than or equal to (\>=)3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
* Participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the Medical Monitor.
* Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy.
* Participant is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment.
* Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
* A participant with negative (as determined by Central Testing Lab) or unevaluable TIM-3 expression from tissue obtained prior to study entry will not be eligible for the study.
* Participant has received prior therapy as defined below:
* Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE.
* Prior treatment with an anti-lymphocyte activation gene (LAG)-3 or anti-TIM-3.
* Radiologic or clinical progression \<= 8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody.
* Participants with known epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) translocation, or receptor tyrosine kinase (ROS1) mutation.
* Participant has received a vaccine other than a vaccine against severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) infection ("Coronavirus Disease 2019" \[COVID-19\]) within 7 days of planned start of study therapy. The use of all COVID-19 vaccines is allowed, with the exception of COVID-19 vaccines using the recombinant adenoviral vector platform within 30 days of planned start of study therapy. If a COVID-19 vaccine using this platform is to be administered within 30 days of planned start of study therapy, this must first be discussed with and approved by the Sponsor's Medical Monitor.
* Participant has been previously treated with an anti PD 1, anti PD L1, or anti PD L2 agent that resulted in permanent discontinuation due to an AE
* Participant has been previously treated with an anti TIM-3 or anti cytotoxic T lymphocyte-associated protein 4 (CTLA 4) agent or docetaxel.
* Participant has a documented sensitizing EGFR, ALK, or ROS-1 mutation. Participants whose tumors have not been tested for these driver mutations and therefore who have unknown driver mutation status are not eligible. Participants with squamous histology do not need to be tested for these driver mutations.
* Participant had radiological or clinical disease progression (that is \[ie,\] worsening performance status, clinical symptoms, and laboratory data) \<=8 weeks after initiation of prior anti PD 1 or anti-PD-L1 antibody. The clinical disease progression should have been confirmed by a subsequent radiological scan.
* Participant has received radiation to the lung that is \>30 Gray (Gy) within 6 months prior to the first dose of study treatment.
* Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment.
* Participant has an additional malignancy or a history of prior malignancy, with the exception of adequately treated basal or squamous skin cancer, cervical carcinoma in situ, or bladder carcinoma in situ without evidence of disease, or had a malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy.
* Participant has known new or progressive brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiologically stable central nervous system disease may participate, provided they are neurologically stable for at least 4 weeks before study entry and are off corticosteroids within 3 days prior to the first dose of study treatment.
* Participant has tested positive for the following at Screening or within 3 months before the first dose of study treatment:
* Presence of hepatitis B surface antigen.
* Presence of hepatitis C antibody in the absence of an Ribonucleic acid (RNA) test for hepatitis C virus.
* Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2 antibodies).
* Participant has active autoimmune disease that required systemic treatment in the past 2 years, is immunocompromised in the opinion of the Investigator, or is receiving systemic immunosuppressive treatment. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy of prednisone, or equivalent, for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
* Participant has received systemic steroid therapy within 3 days prior to the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
* Participant has current interstitial lung disease, current pneumonitis, or a history of pneumonitis that required the use of glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.
* Participant does not meet requirements per local prescribing guidelines for receiving treatment with docetaxel, including severe hypersensitivity reactions to drugs formulated with polysorbate 80.
* Participant has received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half life of the most recent therapy prior to study Day 1, whichever is shorter.
* Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC
* Participant must not have had major surgery \<= 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
* Participants must not have received investigational therapy \<= 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior to initiating protocol therapy.
* Active or untreated central nervous system (CNS) and leptomeningeal metastases
* Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3
* Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components or excipients.
* Participants with active malignancy (other than HCC) or a prior malignancy within the past 2 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
* Participant must not have serious, uncontrolled medical disorder, or nonmalignant systemic disease as determined by the treating physician. Examples include, but are not limited to uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome.
* Has a history or evidence of cardiac abnormalities within the 6 months prior to enrollment, including:
* Serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second-degree (Type II) or third-degree atrioventricular (AV) block.
* Cardiomyopathy, myocarditis, myocardial infarction, acute coronary syndromes (including angina pectoris), coronary angioplasty, stenting, or bypass grafting.
* Congestive heart failure \[New York Heart Association (NYHA) Class III or IV\]
* Symptomatic pericarditis
* Known history of HIV infection
* Active tuberculosis infection or other microbial infection or any active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
* Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (. i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchial asthma, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
* History of organ transplantation including allogeneic bone marrow transplantation
* Participant has a diagnosis of immunodeficiency or has been receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
* Participant has received a live vaccine within 7 days of initiating protocol therapy. Seasonal flu vaccines that do not contain live virus and COVID 19 vaccines are permitted.
* Psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant, lactating, breastfeeding, or intending to become pregnant during the study and for 150 days after the study

Contacts and Locations

Principal Investigator

GSK Clinical Trials

STUDY_DIRECTOR

GlaxoSmithKline

Study Locations (Sites)

GSK Investigational Site

Goodyear, Arizona, 85338

United States

GSK Investigational Site

Scottsdale, Arizona, 85258

United States

GSK Investigational Site

Tucson, Arizona, 85704

United States

GSK Investigational Site

Tucson, Arizona, 85711

United States

GSK Investigational Site

Encinitas, California, 92024

United States

GSK Investigational Site

Fountain Valley, California, 92708

United States

GSK Investigational Site

Los Angeles, California, 90024

United States

GSK Investigational Site

Los Angeles, California, 90025

United States

GSK Investigational Site

San Marcos, California, 92069

United States

GSK Investigational Site

Whittier, California, 90606

United States

GSK Investigational Site

Aurora, Colorado, 80012

United States

GSK Investigational Site

Aurora, Colorado, 80045

United States

GSK Investigational Site

Denver, Colorado, 80218

United States

GSK Investigational Site

New Haven, Connecticut, 06511

United States

GSK Investigational Site

Washington D.C., District of Columbia, 20007

United States

GSK Investigational Site

Jacksonville, Florida, 32224

United States

GSK Investigational Site

Miami, Florida, 33140

United States

GSK Investigational Site

Sarasota, Florida, 34232

United States

GSK Investigational Site

Tampa, Florida, 33612

United States

GSK Investigational Site

Atlanta, Georgia, 30322

United States

GSK Investigational Site

Augusta, Georgia, 30912

United States

GSK Investigational Site

Arlington Heights, Illinois, 60005

United States

GSK Investigational Site

Chicago, Illinois, 60637

United States

GSK Investigational Site

Niles, Illinois, 60714

United States

GSK Investigational Site

Iowa City, Iowa, 52242

United States

GSK Investigational Site

Wichita, Kansas, 67214

United States

GSK Investigational Site

Louisville, Kentucky, 40202

United States

GSK Investigational Site

Pikeville, Kentucky, 41501

United States

GSK Investigational Site

Wheaton, Maryland, 20850

United States

GSK Investigational Site

Boston, Massachusetts, 02114

United States

GSK Investigational Site

Detroit, Michigan, 48202

United States

GSK Investigational Site

Rochester, Minnesota, 55905

United States

GSK Investigational Site

Florissant, Missouri, 63031

United States

GSK Investigational Site

St Louis, Missouri, 63110

United States

GSK Investigational Site

St Louis, Missouri, 63129

United States

GSK Investigational Site

St Louis, Missouri, 63141

United States

GSK Investigational Site

Hackensack, New Jersey, 07601

United States

GSK Investigational Site

New York, New York, 10016

United States

GSK Investigational Site

The Bronx, New York, 10461

United States

GSK Investigational Site

Cincinnati, Ohio, 45242

United States

GSK Investigational Site

Cleveland, Ohio, 44106

United States

GSK Investigational Site

Toledo, Ohio, 43623

United States

GSK Investigational Site

Eugene, Oregon, 97401

United States

GSK Investigational Site

Vancouver, Oregon, 97213-2982

United States

GSK Investigational Site

Bethlehem, Pennsylvania, 18015

United States

GSK Investigational Site

Pittsburgh, Pennsylvania, 15232

United States

GSK Investigational Site

Charleston, South Carolina, 29425

United States

GSK Investigational Site

Greenville, South Carolina, 29605

United States

GSK Investigational Site

Nashville, Tennessee, 37203

United States

GSK Investigational Site

Austin, Texas, 78705

United States

GSK Investigational Site

Dallas, Texas, 75246

United States

GSK Investigational Site

Fort Worth, Texas, 76104

United States

GSK Investigational Site

Houston, Texas, 77030

United States

GSK Investigational Site

Longview, Texas, 75601

United States

GSK Investigational Site

McAllen, Texas, 78503-1298

United States

GSK Investigational Site

San Antonio, Texas, 78229

United States

GSK Investigational Site

Temple, Texas, 76508

United States

GSK Investigational Site

Tyler, Texas, 75702

United States

GSK Investigational Site

Fairfax, Virginia, 22031

United States

GSK Investigational Site

Kennewick, Washington, 99336

United States

GSK Investigational Site

Puyallup, Washington, 98373

United States

GSK Investigational Site

Seattle, Washington, 98111

United States

GSK Investigational Site

Tacoma, Washington, 98405

United States

GSK Investigational Site

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Tesaro, Inc.

GSK Clinical Trials, STUDY_DIRECTOR, GlaxoSmithKline

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2016-07-08

Study Completion Date2027-03-01

Study Record Updates

Study Start Date2016-07-08

Study Completion Date2027-03-01

Terms related to this study

Keywords Provided by Researchers

TSR-022
Nivolumab
Advanced solid tumors
Metastatic solid tumors
Immunotherapy
Colorectal cancer
Non-small cell lung cancer
Melanoma
TSR-033
TSR-042
Hepatocellular carcinoma cancer
Docetaxel

Additional Relevant MeSH Terms

Neoplasms