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

NCT02817633 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2133482018-002143-29
• Study Type: interventional
• Target: 463
• Locations: 3 countries
• Sites: 89

Brief Summary

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.

Conditions

Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Part 1 (a): Number of participants achieving dose limiting toxicity (DLTs)

  Up to 28 days

• Part 1 (b,c,d): Number of participants achieving dose limiting toxicity (DLTs)

  Up to 42 days

• Part 1 (f,g,h): Number of participants achieving dose limiting toxicity (DLTs)

  Up to 21 days

• Part 1: Number of participants with adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, treatment emergent adverse events (TEAEs), TEAEs leading to death and immune-related adverse events (irAEs)

  Up to 2 years

• Part 1: Number of participants with clinically significant changes in laboratory parameters, vital signs, electrocardiogram (ECG) findings, Eastern Cooperative Oncology Group (ECOG) status, physical examination and use of concomitant medications

  Up to 2 years

• Part 1 (e) and Part 2: Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

  Up to 2 years

Secondary Outcomes (45)

• Part 1 (a, b, c, d, f, g, h): ORR by RECIST v 1.1

  Up to 2 years

• Part 2 (A, B, C, D): ORR by Immune related RECIST (irRECIST)

  Up to 2 years

• Part 2: Duration of response (DOR) by RECIST v 1.1

  Up to 2 years

• Part 2 (A, B, C, D): DOR by irRECIST

  Up to 2 years

• Parts 1 and 2: Disease control rate (DCR) by RECIST v 1.1

  Up to 2 years

Study Arms (17)

Part 1a: TSR-022 monotherapy

EXPERIMENTAL

Drug: TSR-022

Part 1b: TSR-022 in combination with nivolumab

EXPERIMENTAL

Drug: TSR-022; Drug: Nivolumab

Part 1c: TSR-022 in combination with TSR-042

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Part 1d: TSR-022 in combination with TSR-042 and TSR-033

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042; Drug: TSR-033

Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Part 1f: TSR-022 in combination with TSR-042 and Docetaxel

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042; Drug: Docetaxel

Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042; Drug: Pemetrexed; Drug: Cisplatin

Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042; Drug: Pemetrexed; Drug: Carboplatin

Part 2: Cohort A Melanoma-TSR-022 as monotherapy

EXPERIMENTAL

Drug: TSR-022

Part 2: Cohort A Melanoma-TSR-022 with TSR-042

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy

EXPERIMENTAL

Drug: TSR-022

Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy

EXPERIMENTAL

Drug: TSR-022

Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel

EXPERIMENTAL

Drug: TSR-022; Drug: Docetaxel

Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042

EXPERIMENTAL

Drug: TSR-022; Drug: TSR-042

Interventions

TSR-022 DRUG

TSR-022 will be administered.

Part 1a: TSR-022 monotherapy; Part 1b: TSR-022 in combination with nivolumab; Part 1c: TSR-022 in combination with TSR-042; Part 1d: TSR-022 in combination with TSR-042 and TSR-033; Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1); Part 1f: TSR-022 in combination with TSR-042 and Docetaxel; Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin; Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin; Part 2: Cohort A Melanoma-TSR-022 as monotherapy; Part 2: Cohort A Melanoma-TSR-022 with TSR-042; Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042; Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel; Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042; Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042; Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy; Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy; Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042

Nivolumab DRUG

Nivolumab will be administered.

Part 1b: TSR-022 in combination with nivolumab

TSR-042 DRUG

TSR-042 will be administered.

Part 1c: TSR-022 in combination with TSR-042; Part 1d: TSR-022 in combination with TSR-042 and TSR-033; Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1); Part 1f: TSR-022 in combination with TSR-042 and Docetaxel; Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin; Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin; Part 2: Cohort A Melanoma-TSR-022 with TSR-042; Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042; Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042; Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042; Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042

TSR-033 DRUG

TSR-033 will be administered.

Part 1d: TSR-022 in combination with TSR-042 and TSR-033

Docetaxel DRUG

Docetaxel will be administered.

Part 1f: TSR-022 in combination with TSR-042 and Docetaxel; Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel

Pemetrexed DRUG

Pemetrexed will be administered.

Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin; Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin

Cisplatin DRUG

Cisplatin will be administered.

Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin

Carboplatin DRUG

Carboplatin will be administered.

Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin

Eligibility Criteria

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

You may qualify if:

• Participant is at least 18 years of age.
• Female participants of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication or be of non-childbearing potential.
• Participant has an ECOG performance status of less than or equal to (\<=)1.
• Participant has adequate organ function.
• Participant with advanced or metastatic solid tumor who meets the requirements for the part of the study/cohort he/she will participate in, as follows:
• Participants with advanced or metastatic non-small cell lung carcinoma (NSCLC) that is measurable by CT or MRI per RECIST version 1.1 criteria and meet the following criteria:
• NSCLC histology includes squamous or non-squamous cell carcinoma.
• Participants have received no more than 2 prior lines of therapy, which must include a platinum-based chemotherapy (for example \[e.g.\], cisplatin, carboplatin) and an anti- programmed death-ligand 1 (PD-L1) antibody.
• Participants must have documented radiographic progression by RECIST version 1.1 criteria on prior anti-programmed cell death protein (PD-1) or anti-PD-L1 therapy.
• Biopsies -All participants enrolled must undergo a biopsy prior to study entry, and the biopsy tissue must be submitted to the central laboratory for all participants in order to determine T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) expression level prior to first dose. If a participant has had a biopsy prior to entering the 35-day screening period and within approximately 12 weeks of study treatment, that biopsy may be accepted as the Baseline fresh biopsy.
• Participant is greater than or equal to (\>=)18 years old, is able to understand the study procedures, and agrees to participate in the study by providing written informed consent which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and protocol.
• Participant has histologically or cytologically proven advanced or metastatic NSCLC, and only squamous or non-squamous cell carcinoma.
• Participant has received no more than 2 prior lines of therapy for advanced or metastatic disease, which must only include a platinum-based (eg, cisplatin, carboplatin) doublet chemotherapy regimen and an anti-PD-1 or anti-PD-L1 antibody (no other biologic agents alone or in combination; novel combinations are not allowed). Participants previously treated with targeted therapies, including angiogenesis inhibitors (eg, bevacizumab, ramucirumab, lenvatinib), are not eligible.
• Participant has measurable disease, that is, presenting with at least 1 measurable lesion per RECIST v1.1 as determined by the local site Investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if disease progression has been demonstrated in such lesions and if there are other target lesions. If there is only 1 target lesion that was previously irradiated, the participant is not eligible.
• Participant has documented radiological disease progression on prior platinum-based chemotherapy and on prior anti-PD-1 or anti-PD-L1 therapy according to RECIST v1.1.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tesaro, Inc.: lead

Study Sites (89)

GSK Investigational Site

Goodyear, Arizona, 85338, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85258, United States

Location

GSK Investigational Site

Tucson, Arizona, 85704, United States

Location

GSK Investigational Site

Tucson, Arizona, 85711, United States

Location

GSK Investigational Site

Encinitas, California, 92024, United States

Location

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

Los Angeles, California, 90024, United States

Location

GSK Investigational Site

Los Angeles, California, 90025, United States

Location

GSK Investigational Site

San Marcos, California, 92069, United States

Location

GSK Investigational Site

Whittier, California, 90606, United States

Location

GSK Investigational Site

Aurora, Colorado, 80012, United States

Location

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Denver, Colorado, 80218, United States

Location

GSK Investigational Site

New Haven, Connecticut, 06511, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32224, United States

Location

GSK Investigational Site

Miami, Florida, 33140, United States

Location

GSK Investigational Site

Sarasota, Florida, 34232, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Arlington Heights, Illinois, 60005, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Niles, Illinois, 60714, United States

Location

GSK Investigational Site

Iowa City, Iowa, 52242, United States

Location

GSK Investigational Site

Wichita, Kansas, 67214, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40202, United States

Location

GSK Investigational Site

Pikeville, Kentucky, 41501, United States

Location

GSK Investigational Site

Wheaton, Maryland, 20850, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Florissant, Missouri, 63031, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

St Louis, Missouri, 63129, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Hackensack, New Jersey, 07601, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

The Bronx, New York, 10461, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45242, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Toledo, Ohio, 43623, United States

Location

GSK Investigational Site

Eugene, Oregon, 97401, United States

Location

GSK Investigational Site

Vancouver, Oregon, 97213-2982, United States

Location

GSK Investigational Site

Bethlehem, Pennsylvania, 18015, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15232, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29605, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Longview, Texas, 75601, United States

Location

GSK Investigational Site

McAllen, Texas, 78503-1298, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Temple, Texas, 76508, United States

Location

GSK Investigational Site

Tyler, Texas, 75702, United States

Location

GSK Investigational Site

Fairfax, Virginia, 22031, United States

Location

GSK Investigational Site

Kennewick, Washington, 99336, United States

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GSK Investigational Site

Puyallup, Washington, 98373, United States

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GSK Investigational Site

Seattle, Washington, 98111, United States

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GSK Investigational Site

Tacoma, Washington, 98405, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53792, United States

Location

GSK Investigational Site

Daegu, 42601, South Korea

Location

GSK Investigational Site

Seoul, 02841, South Korea

Location

GSK Investigational Site

Seoul, 03722, South Korea

Location

GSK Investigational Site

Seoul, 06351, South Korea

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GSK Investigational Site

Seoul, 7061, South Korea

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GSK Investigational Site

Barcelona, 08017, Spain

Location

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

Barcelona, 8035, Spain

Location

GSK Investigational Site

Girona, 17007, Spain

Location

GSK Investigational Site

Jerez de la Frontera, 11407, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobrega, 08908, Spain

Location

GSK Investigational Site

Las Palmas de Gran Canar, 35016, Spain

Location

GSK Investigational Site

Madrid, 28027, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Madrid, 28222, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07120, Spain

Location

GSK Investigational Site

Pamplona, 31008, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma

Interventions

Nivolumab; dostarlimab; TSR-033; Docetaxel; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Click here to enter text.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-center, open-label, first-in-human Phase 1 study.

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: June 29, 2016
• Study Start: July 8, 2016
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (20); US (64); KR (5)