A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)
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ClinicalTrials.gov Identifier: NCT02817633 |
Recruitment Status :
Recruiting
First Posted : June 29, 2016
Last Update Posted : May 2, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Neoplasms | Drug: TSR-022 Drug: Nivolumab Drug: TSR-042 Drug: TSR-033 Drug: Docetaxel Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 369 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | This is a multi-center, open-label, first-in-human Phase 1 study. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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) |
Actual Study Start Date : | July 8, 2016 |
Estimated Primary Completion Date : | October 5, 2023 |
Estimated Study Completion Date : | October 3, 2024 |
Arm | Intervention/treatment |
---|---|
Experimental: Part 1a: TSR-022 monotherapy |
Drug: TSR-022
TSR-022 will be administered. |
Experimental: Part 1b: TSR-022 in combination with nivolumab |
Drug: TSR-022
TSR-022 will be administered. Drug: Nivolumab Nivolumab will be administered. |
Experimental: Part 1c: TSR-022 in combination with TSR-042 |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. |
Experimental: Part 1d: TSR-022 in combination with TSR-042 and TSR-033 |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: TSR-033 TSR-033 will be administered. |
Experimental: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1) |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. |
Experimental: Part 1f: TSR-022 in combination with TSR-042 and Docetaxel |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: Docetaxel Docetaxel will be administered. |
Experimental: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: Pemetrexed Drug: Cisplatin |
Experimental: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: Pemetrexed Drug: Carboplatin |
Experimental: Part 2: Cohort A Melanoma-TSR-022 as monotherapy |
Drug: TSR-022
TSR-022 will be administered. |
Experimental: Part 2: Cohort A Melanoma-TSR-022 with TSR-042 |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. |
Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy |
Drug: TSR-022
TSR-022 will be administered. |
Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042 |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. |
Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy |
Drug: TSR-022
TSR-022 will be administered. |
Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042 |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. |
Experimental: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC) |
Drug: TSR-022
TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. |
- Part 1 (a): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 28 days ]
- Part 1 (b,c,d): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 42 days ]
- Part 1 (f,g,h): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 2 years ]
- Part 1 (c, d, e, f, g, h): Number of participants with anti-TSR-022, anti-TSR-042 [ Time Frame: Up to 2 years ]
- Part 1 (d): Number of participants with anti-TSR-033 antibodies [ Time Frame: Up to 2 years ]
- Part 1 (a, b, c, d, f, g, h): ORR by RECIST v 1.1 [ Time Frame: Up to 2 years ]
- Part 2: ORR by Immune related RECIST (irRECIST) [ Time Frame: Up to 2 years ]
- Part 2: Duration of response (DOR) by RECIST v 1.1 and irRECIST [ Time Frame: Up to 2 years ]
- Parts 1 and 2: Disease control rate (DCR) by RECIST v 1.1 [ Time Frame: Up to 2 years ]
- Part 2: DCR by irRECIST [ Time Frame: Up to 2 years ]
- Part 2: Progression-free survival (PFS) by RECIST v 1.1 and irRECIST [ Time Frame: Up to 2 years ]
- Parts 1 and 2: Serum concentration of TSR-022 [ Time Frame: Up to 2 years ]
- Part 1d: Serum concentration of TSR-033 [ Time Frame: Up to 2 years ]
- Part 1 (c, d, e, f, g ,h): Serum concentration of TSR-042 [ Time Frame: Up to 2 years ]
- Part 2: Serum concentration of TSR-042 [ Time Frame: Up to 2 years ]
- Part 2: Overall survival (OS) [ Time Frame: Up to 2 years ]
- Part 1a: Minimum plasma concentration (Cmin) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
- Part 1b: Cmin of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
- Part 1c: Cmin of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
- Part 1d: Cmin of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
- Part 1a: Area under the concentration × time curve from time 0 to infinity AUC (0-inf) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
- Part 1b: AUC (0-inf) of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
- Part 1c: AUC (0-inf) of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
- Part 1d: AUC (0-inf) of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
- Part 1a: Area under the concentration time curve from time 0 to last assessment (AUC 0-last) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
- Part 1b: AUC (0-last) of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
- Part 1c: AUC (0-last) of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
- Part 1d: AUC (0-last) of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
- Part 1a: Terminal half life (1/2) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
- Part 1b: t1/2 of TSR-022 and in combination with nivolumab [ Time Frame: Up to 2 years ]
- Part 1c: t1/2 of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
- Part 1d: t1/2 TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
- Part 1a: Area under the concentration × time curve during the dosing interval (AUCtau) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
- Part 1b: AUCtau of TSR-022 and in combination with nivolumab [ Time Frame: Up to 2 years ]
- Part 1c: AUCtau of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
- Part 1d: AUCtau of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
- Part 1: Number of participants with anti-drug antibodies (ADAs) to TSR-022 [ Time Frame: Up to 2 years ]
- Part 2: Number of participants with ADA to anti-TSR-022 [ Time Frame: Up to 2 years ]
- Part 1 (c, d, e, f, g ,h): Number of participants with ADA to TSR-042 [ Time Frame: Up to 2 years ]
- Part 2: Number of Participants with ADA to TSR-042 [ Time Frame: Up to 2 years ]
- Part 1d: Number of participants with ADA to TSR-033 [ Time Frame: Up to 2 years ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
- 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.
Inclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C:
- 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:
- Part 2: Histologically proven advanced (unresectable) or metastatic solid tumor that is measurable by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST version 1.1 criteria
- Inclusion Criteria for Participants in Part 2 Cohort D
- Participants with advanced or metastatic 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-PD-(L)1 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-(L)1 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 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.
Exclusion Criteria
- 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, nonmalignant 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.
Exclusion Criteria for Participants in Part 2 Cohort D
- 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 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02817633
Contact: US GSK Clinical Trials Call Cente | 877-379-3718 | GSKClinicalSupportHD@gsk.com | |
Contact: EU GSK Clinical Trials Call Center | +44 (0) 20 89904466 | GSKClinicalSupportHD@gsk.com |

Study Director: | GSK Clinical Trials | GlaxoSmithKline |
Responsible Party: | Tesaro, Inc. |
ClinicalTrials.gov Identifier: | NCT02817633 |
Other Study ID Numbers: |
213348 4020-01-001 ( Other Identifier: Tesaro ) |
First Posted: | June 29, 2016 Key Record Dates |
Last Update Posted: | May 2, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
TSR-022 Nivolumab Advanced solid tumors Metastatic solid tumors Immunotherapy |
Colorectal cancer Non-small cell lung cancer Melanoma TSR-033 TSR-042 |
Carboplatin Docetaxel Nivolumab Pemetrexed Antineoplastic Agents Tubulin Modulators Antimitotic Agents |
Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |