June 22, 2016
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June 29, 2016
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May 2, 2022
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July 8, 2016
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October 5, 2023 (Final data collection date for primary outcome measure)
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- 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 ]
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- Safety and tolerability of TSR-022 using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced solid tumors [ Time Frame: Part 1 Dose Escalation - Approximately 2 years ]
- Anti-tumor activity of TSR-022 in patients with solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 [ Time Frame: Part 2 Expansion - Approximately 2 years ]
- Recommended Phase 2 dose (RP2D) and schedule as monotherapy and in combination with an anti-PD-1 antibody [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
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- 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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- Safety and tolerability of TSR-022 using CTCAE v.4.03 [ Time Frame: Part 2 - Approximately 2 years ]
Incidence of treatment-emergent AEs (TEAEs), SAEs, immune-related AEs (irAEs), TEAEs leading to death, and AEs leading to discontinuation occurring while patients are on treatment or up to 90 days after the last dose of study drug as assessed by CTCAE v4.03
- Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- Duration of response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- Disease control rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- Overall survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: AUC, 0-last assessment [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: AUC, 0 to infinity [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: AUC at steady state [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: Minimum Concentration (Cmin) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: Clearance (CL) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: Cmin at steady state (Cmin,ss) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: Cmax at steady state (Cmax, ss) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: Volume of Distribution (Vz) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- PK Parameter: terminal half-life (t1/2) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
- Pharmacodynamic profile as assessed by receptor occupancy [ Time Frame: Part 1 and 2 - Approximately 4 years ]
- Immunogenicity as assessed by the presence of anti-drug antibodies [ Time Frame: Part 1 and 2 -Approximately 4 years ]
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Not Provided
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Not Provided
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A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)
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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)
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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.
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Not Provided
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Interventional
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Phase 1
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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
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Neoplasms
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- Drug: TSR-022
TSR-022 will be administered.
- Drug: Nivolumab
Nivolumab will be administered.
- Drug: TSR-042
TSR-042 will be administered.
- Drug: TSR-033
TSR-033 will be administered.
- Drug: Docetaxel
Docetaxel will be administered.
- Drug: Pemetrexed
- Drug: Cisplatin
- Drug: Carboplatin
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- Experimental: Part 1a: TSR-022 monotherapy
Intervention: Drug: TSR-022
- Experimental: Part 1b: TSR-022 in combination with nivolumab
Interventions:
- Drug: TSR-022
- Drug: Nivolumab
- Experimental: Part 1c: TSR-022 in combination with TSR-042
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Experimental: Part 1d: TSR-022 in combination with TSR-042 and TSR-033
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Drug: TSR-033
- Experimental: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Experimental: Part 1f: TSR-022 in combination with TSR-042 and Docetaxel
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Drug: Docetaxel
- Experimental: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Drug: Pemetrexed
- Drug: Cisplatin
- Experimental: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Drug: Pemetrexed
- Drug: Carboplatin
- Experimental: Part 2: Cohort A Melanoma-TSR-022 as monotherapy
Intervention: Drug: TSR-022
- Experimental: Part 2: Cohort A Melanoma-TSR-022 with TSR-042
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy
Intervention: Drug: TSR-022
- Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy
Intervention: Drug: TSR-022
- Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042
Interventions:
- Drug: TSR-022
- Drug: TSR-042
- Experimental: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)
Interventions:
- Drug: TSR-022
- Drug: TSR-042
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Not Provided
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Recruiting
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369
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402
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October 3, 2024
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October 5, 2023 (Final data collection date for primary outcome measure)
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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.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Spain, United States
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NCT02817633
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213348 4020-01-001 ( Other Identifier: Tesaro )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Tesaro, Inc.
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Same as current
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Tesaro, Inc.
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Same as current
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Not Provided
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Study Director: |
GSK Clinical Trials |
GlaxoSmithKline |
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Tesaro, Inc.
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April 2022
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