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)

Who is this study for? Patients with Neoplasms
Status: Recruiting
Location: See all (95) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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:

• 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 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.

• Participant agrees to submit an archival formalin fixed paraffin embedded (FFPE) tumor tissue specimen that was collected on or after diagnosis of metastatic disease from location(s) not irradiated prior to biopsy. Both tissue block and freshly cut slides are acceptable. If archival tissue is not available, the participant must undergo biopsy prior to study entry.

• Participant has an ECOG performance status score of 0 or 1.

• Participant has a life expectancy of at least 3 months and is anticipated to be able to complete 4 cycles of docetaxel treatment.

• Participant has adequate organ function as defined in the protocol

• Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Histologically confirmed locally advanced or metastatic and/or unresectable Hepatocellcular Carcinoma (HCC)

‣ Barcelona Clinic Liver Cancer Stage B or C

⁃ Cirrhosis grade of Child-Pugh Class A

• No prior systemic therapy for HCC

• Documented HBV testing at screening, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAB) and hepatitis B core antibody (HBcAb). Participants with a positive HBsAg will require negative hepatitis B virus (HBV) DNA testing at screening.

‣ Participants with chronic HBV infection (HBsAg +) are required to be receiving effective antiviral therapy (i.e., with Tenofovir or Entecavir) for at least 14 days with willingness to continue for the length of the study and have HBV deoxyribonucleic acid (DNA) less than 100 International Units Per Milliliter (IU/mL) within 28 days prior to initiation of study treatment.

⁃ Participants with chronic HBV infection (HBsAg+) require documented Hepatitis D virus (HDV) antibody testing conducted at screening. If HDV antibody is positive, then HDV ribonucleic acid (RNA) must be negative to participate.

⁃ Participants with a negative HBsAg and positive HBcAb result are eligible only if HBV DNA is negative (Past HBV participants).

• Documented hepatitis C virus (HCV) antibody testing conducted at screening. If HCV antibody is positive, then HCV RNA must be negative. Participants with recently treated HCV prior to study start must be greater than (\>)12 weeks from final HCV treatment.

• Must have measurable disease, defined as at least one tumor lesion that can be accurately measured according to RECIST v1.1

• Participant agrees to submit an archival FFPE tumor tissue specimen that was collected on or after diagnosis of metastatic disease from location(s) not irradiated prior to biopsy. Both tissue block and freshly cut slides are acceptable. If archival tissue is not available, the participant must undergo biopsy prior to study entry.

• • Participants are also encouraged, but not required, to have a fresh tumor tissue biopsy of a primary or metastatic tumor prior to dosing (samples will be used to enable biomarker analysis).

• International normalized ratio (INR) or prothrombin time (PT) \<= 2× upper limit of normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) \<=2×ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

• Negative human immunodeficiency virus (HIV) test at screening The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

Locations
United States
Arizona
GSK Investigational Site
COMPLETED
Goodyear
GSK Investigational Site
COMPLETED
Scottsdale
GSK Investigational Site
COMPLETED
Tucson
GSK Investigational Site
COMPLETED
Tucson
California
GSK Investigational Site
RECRUITING
Encinitas
GSK Investigational Site
RECRUITING
Fountain Valley
GSK Investigational Site
RECRUITING
Los Angeles
GSK Investigational Site
RECRUITING
Los Angeles
GSK Investigational Site
RECRUITING
Whittier
Colorado
GSK Investigational Site
RECRUITING
Aurora
GSK Investigational Site
RECRUITING
Aurora
GSK Investigational Site
RECRUITING
Denver
GSK Investigational Site
COMPLETED
Denver
Connecticut
GSK Investigational Site
COMPLETED
New Haven
Washington, D.c.
GSK Investigational Site
COMPLETED
Washington D.c.
Florida
GSK Investigational Site
COMPLETED
Jacksonville
GSK Investigational Site
COMPLETED
Miami Beach
GSK Investigational Site
RECRUITING
Sarasota
GSK Investigational Site
RECRUITING
Tampa
Georgia
GSK Investigational Site
COMPLETED
Atlanta
GSK Investigational Site
COMPLETED
Augusta
Iowa
GSK Investigational Site
RECRUITING
Iowa City
Illinois
GSK Investigational Site
COMPLETED
Arlington Heights
GSK Investigational Site
RECRUITING
Chicago
GSK Investigational Site
COMPLETED
Niles
Kansas
GSK Investigational Site
COMPLETED
Wichita
Kentucky
GSK Investigational Site
COMPLETED
Louisville
GSK Investigational Site
RECRUITING
Pikeville
Massachusetts
GSK Investigational Site
RECRUITING
Boston
GSK Investigational Site
COMPLETED
Boston
Maryland
GSK Investigational Site
RECRUITING
Rockville
Michigan
GSK Investigational Site
COMPLETED
Detroit
Minnesota
GSK Investigational Site
COMPLETED
Rochester
Missouri
GSK Investigational Site
RECRUITING
St Louis
New Jersey
GSK Investigational Site
COMPLETED
Hackensack
New York
GSK Investigational Site
RECRUITING
New York
GSK Investigational Site
RECRUITING
The Bronx
Ohio
GSK Investigational Site
COMPLETED
Cincinnati
GSK Investigational Site
RECRUITING
Cleveland
GSK Investigational Site
RECRUITING
Toledo
Oregon
GSK Investigational Site
RECRUITING
Eugene
GSK Investigational Site
COMPLETED
Portland
Pennsylvania
GSK Investigational Site
COMPLETED
Bethlehem
GSK Investigational Site
RECRUITING
Pittsburgh
South Carolina
GSK Investigational Site
RECRUITING
Charleston
GSK Investigational Site
COMPLETED
Greenville
Tennessee
GSK Investigational Site
RECRUITING
Nashville
Texas
GSK Investigational Site
COMPLETED
Austin
GSK Investigational Site
RECRUITING
Dallas
GSK Investigational Site
COMPLETED
Fort Worth
GSK Investigational Site
RECRUITING
Houston
GSK Investigational Site
RECRUITING
Longview
GSK Investigational Site
COMPLETED
Mcallen
GSK Investigational Site
COMPLETED
San Antonio
GSK Investigational Site
RECRUITING
San Marcos
GSK Investigational Site
COMPLETED
Temple
GSK Investigational Site
RECRUITING
Tyler
GSK Investigational Site
RECRUITING
Weslaco
Virginia
GSK Investigational Site
RECRUITING
Fairfax
Washington
GSK Investigational Site
COMPLETED
Kennewick
GSK Investigational Site
RECRUITING
Puyallup
GSK Investigational Site
RECRUITING
Seattle
GSK Investigational Site
COMPLETED
Tacoma
Wisconsin
GSK Investigational Site
COMPLETED
Madison
Other Locations
Republic of Korea
GSK Investigational Site
RECRUITING
Busan
GSK Investigational Site
RECRUITING
Daegu
GSK Investigational Site
RECRUITING
Seongnam-si, Gyeonggi-do
GSK Investigational Site
RECRUITING
Seoul
GSK Investigational Site
RECRUITING
Seoul
GSK Investigational Site
RECRUITING
Seoul
GSK Investigational Site
RECRUITING
Seoul
Spain
GSK Investigational Site
RECRUITING
Barcelona
GSK Investigational Site
RECRUITING
Barcelona
GSK Investigational Site
RECRUITING
Barcelona
GSK Investigational Site
RECRUITING
Barcelona
GSK Investigational Site
RECRUITING
Girona
GSK Investigational Site
RECRUITING
Jerez De La Frontera
GSK Investigational Site
RECRUITING
L'hospitalet De Llobregat
GSK Investigational Site
RECRUITING
Las Palmas De Gran Canaria
GSK Investigational Site
RECRUITING
Madrid
GSK Investigational Site
COMPLETED
Madrid
GSK Investigational Site
COMPLETED
Madrid
GSK Investigational Site
RECRUITING
Madrid
GSK Investigational Site
RECRUITING
Majadahonda (madrid)
GSK Investigational Site
RECRUITING
Málaga
GSK Investigational Site
RECRUITING
Palma De Mallorca
GSK Investigational Site
COMPLETED
Pamplona
GSK Investigational Site
RECRUITING
Santander
GSK Investigational Site
RECRUITING
Seville
GSK Investigational Site
RECRUITING
Valencia
GSK Investigational Site
RECRUITING
Valencia
GSK Investigational Site
RECRUITING
Zaragoza
Taiwan
GSK Investigational Site
RECRUITING
Taichung
GSK Investigational Site
RECRUITING
Tainan City
GSK Investigational Site
RECRUITING
Tainan City
Contact Information
Primary
US GSK Clinical Trials Call Cente
GSKClinicalSupportHD@gsk.com
877-379-3718
Backup
EU GSK Clinical Trials Call Center
GSKClinicalSupportHD@gsk.com
+44 (0) 20 89904466
Time Frame
Start Date: 2016-07-08
Estimated Completion Date: 2027-04-27
Participants
Target number of participants: 447
Treatments
Experimental: Part 1a: TSR-022 monotherapy
Experimental: Part 1b: TSR-022 in combination with nivolumab
Experimental: Part 1c: TSR-022 in combination with TSR-042
Experimental: Part 1d: TSR-022 in combination with TSR-042 and TSR-033
Experimental: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)
Experimental: Part 1f: TSR-022 in combination with TSR-042 and Docetaxel
Experimental: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
Experimental: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
Experimental: Part 2: Cohort A Melanoma-TSR-022 as monotherapy
Experimental: Part 2: Cohort A Melanoma-TSR-022 with TSR-042
Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy
Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042
Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy
Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042
Experimental: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042
Experimental: Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel
Experimental: Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042
Sponsors
Leads: Tesaro, Inc.

This content was sourced from clinicaltrials.gov

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