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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02817633
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : May 2, 2022
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

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.

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

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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.




Primary Outcome Measures :
  1. Part 1 (a): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 28 days ]
  2. Part 1 (b,c,d): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 42 days ]
  3. Part 1 (f,g,h): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 21 days ]
  4. 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 ]
  5. 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 ]
  6. 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 ]

Secondary Outcome Measures :
  1. Part 1 (c, d, e, f, g, h): Number of participants with anti-TSR-022, anti-TSR-042 [ Time Frame: Up to 2 years ]
  2. Part 1 (d): Number of participants with anti-TSR-033 antibodies [ Time Frame: Up to 2 years ]
  3. Part 1 (a, b, c, d, f, g, h): ORR by RECIST v 1.1 [ Time Frame: Up to 2 years ]
  4. Part 2: ORR by Immune related RECIST (irRECIST) [ Time Frame: Up to 2 years ]
  5. Part 2: Duration of response (DOR) by RECIST v 1.1 and irRECIST [ Time Frame: Up to 2 years ]
  6. Parts 1 and 2: Disease control rate (DCR) by RECIST v 1.1 [ Time Frame: Up to 2 years ]
  7. Part 2: DCR by irRECIST [ Time Frame: Up to 2 years ]
  8. Part 2: Progression-free survival (PFS) by RECIST v 1.1 and irRECIST [ Time Frame: Up to 2 years ]
  9. Parts 1 and 2: Serum concentration of TSR-022 [ Time Frame: Up to 2 years ]
  10. Part 1d: Serum concentration of TSR-033 [ Time Frame: Up to 2 years ]
  11. Part 1 (c, d, e, f, g ,h): Serum concentration of TSR-042 [ Time Frame: Up to 2 years ]
  12. Part 2: Serum concentration of TSR-042 [ Time Frame: Up to 2 years ]
  13. Part 2: Overall survival (OS) [ Time Frame: Up to 2 years ]
  14. Part 1a: Minimum plasma concentration (Cmin) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  15. Part 1b: Cmin of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
  16. Part 1c: Cmin of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  17. Part 1d: Cmin of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  18. 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 ]
  19. Part 1b: AUC (0-inf) of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
  20. Part 1c: AUC (0-inf) of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  21. Part 1d: AUC (0-inf) of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  22. 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 ]
  23. Part 1b: AUC (0-last) of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
  24. Part 1c: AUC (0-last) of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  25. Part 1d: AUC (0-last) of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  26. Part 1a: Terminal half life (1/2) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  27. Part 1b: t1/2 of TSR-022 and in combination with nivolumab [ Time Frame: Up to 2 years ]
  28. Part 1c: t1/2 of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  29. Part 1d: t1/2 TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  30. Part 1a: Area under the concentration × time curve during the dosing interval (AUCtau) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  31. Part 1b: AUCtau of TSR-022 and in combination with nivolumab [ Time Frame: Up to 2 years ]
  32. Part 1c: AUCtau of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  33. Part 1d: AUCtau of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  34. Part 1: Number of participants with anti-drug antibodies (ADAs) to TSR-022 [ Time Frame: Up to 2 years ]
  35. Part 2: Number of participants with ADA to anti-TSR-022 [ Time Frame: Up to 2 years ]
  36. Part 1 (c, d, e, f, g ,h): Number of participants with ADA to TSR-042 [ Time Frame: Up to 2 years ]
  37. Part 2: Number of Participants with ADA to TSR-042 [ Time Frame: Up to 2 years ]
  38. Part 1d: Number of participants with ADA to TSR-033 [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
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

Locations
Show Show 73 study locations
Sponsors and Collaborators
Tesaro, Inc.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tesaro, Inc.:
TSR-022
Nivolumab
Advanced solid tumors
Metastatic solid tumors
Immunotherapy
Colorectal cancer
Non-small cell lung cancer
Melanoma
TSR-033
TSR-042
Additional relevant MeSH terms:
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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