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Study of the Safety and Effectiveness of GSK6097608 in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04446351
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : November 24, 2021
Sponsor:
Collaborator:
23andMe, Inc.
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. This study will be used to define the recommended Phase 2 dose (RP2D). The study comprises 3 phases; screening phase (28 days prior to first dose), treatment phase (until disease progression, unacceptable toxicity, death, or withdrawal of consent) and follow-up phase (90 days).

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK6097608 Drug: Dostarlimab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Eligible participants will receive an intravenous (IV) infusion of GSK6097608 every 3 weeks as monotherapy (Arm A) in escalating doses. Once a dose of GSK6097608 has been identified, enrollment in the combination arm (Arm B) will begin. Escalating doses of GSK6097608 will be evaluated with a fixed dosing regimen of dostarlimab given as an IV infusion at the end of GSK6097608 IV infusion. In each arm, a PK/PD cohort will be enrolled at the RP2D. In addition, the safety, PK, and preliminary anticancer activity of dostarlimab monotherapy (Arm D) will be evaluated
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 First-Time-in-Human, Open-Label Study of GSK6097608 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors
Actual Study Start Date : June 25, 2020
Estimated Primary Completion Date : February 17, 2023
Estimated Study Completion Date : February 17, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Dostarlimab

Arm Intervention/treatment
Experimental: Participants receiving GSK6097608 monotherapy (Arm A)
Participants will be administered an IV infusion of GSK6097608 every 3 weeks as monotherapy in escalating doses.
Drug: GSK6097608
GSK6097608 will be administered as an IV infusion.

Experimental: Participants receiving GSK6097608 plus dostarlimab (Arm B)
Participants will be administered an IV infusion of GSK6097608 every 3 weeks in escalating doses followed by an IV infusion of dostarlimab (every 3 weeks for 4 doses and every 6 weeks thereafter).
Drug: GSK6097608
GSK6097608 will be administered as an IV infusion.

Drug: Dostarlimab
Dostarlimab will be administered as an IV infusion.

Experimental: Participants receiving dostarlimab monotherapy (Arm D)
Participants will be administered an IV infusion of dostarlimab monotherapy (1 cohort will receive dostarlimab every 3 weeks and 1 cohort will receive dostarlimab every 6 weeks).
Drug: Dostarlimab
Dostarlimab will be administered as an IV infusion.




Primary Outcome Measures :
  1. Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Up to Day 21 ]
  2. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings [ Time Frame: Up to 2 years ]
  2. Number of participants with dose reductions or delay [ Time Frame: Up to 2 years ]
  3. Number of participants withdrawn due to AEs [ Time Frame: Up to 2 years ]
  4. Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 2 years ]
  5. Arm D only: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST) [ Time Frame: Up to 2 years ]
  6. Arm D only: Disease Control Rate (DCR) based on RECIST 1.1 [ Time Frame: Up to 2 years ]
  7. Arm D only: DCR based on iRECIST [ Time Frame: Up to 2 years ]
  8. Arm D only: Time to response (TTR) based on RECIST 1.1 [ Time Frame: Up to 2 years ]
  9. Arm D only: TTR based on iRECIST [ Time Frame: Up to 2 years ]
  10. Arm D only: Duration of response (DOR) based on RECIST 1.1 [ Time Frame: Up to 2 years ]
  11. Arm D only: DOR based on iRECIST [ Time Frame: Up to 2 years ]
  12. Arm D only: Time to progression (TTP) based on RECIST 1.1 [ Time Frame: Up to 2 years ]
  13. Arm D only: TTP based on iRECIST [ Time Frame: Up to 2 years ]
  14. Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608 [ Time Frame: Up to 2 years ]
  15. Titers of ADAs against GSK6097608 [ Time Frame: Up to 2 years ]
  16. Number of participants with positive ADAs against dostarlimab [ Time Frame: Up to 2 years ]
  17. Titers of ADAs against dostarlimab [ Time Frame: Up to 2 years ]
  18. Maximum observed concentration (Cmax) for GSK6097608 [ Time Frame: Up to 2 years ]
  19. Minimum observed concentration (Cmin) for GSK6097608 [ Time Frame: Up to 2 years ]
  20. Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for GSK6097608 [ Time Frame: Up to 2 years ]
  21. Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for GSK6097608 [ Time Frame: Up to 2 years ]
  22. Apparent terminal phase half-life (t1/2) for GSK6097608 [ Time Frame: Up to 2 years ]
  23. Cmax for dostarlimab [ Time Frame: Up to 2 years ]
  24. Cmin for dostarlimab [ Time Frame: Up to 2 years ]
  25. AUC(0-infinity) for dostarlimab [ Time Frame: Up to 2 years ]
  26. AUC(0-t) for dostarlimab [ Time Frame: Up to 2 years ]
  27. t1/2 for dostarlimab [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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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:

  • Adults 18 years of age or older;
  • Female participants of childbearing potential must agree to use a highly effective form of contraception;
  • Histological or cytological documentation of locally advanced, recurrent, or metastatic solid malignancy;
  • Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists;
  • Participants in a PK/PD cohort must provide a tumor biopsy during the screening period from a tumor lesion and agree to an additional on-treatment biopsy.
  • Measurable disease per RECIST 1.1
  • Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1
  • Life expectancy of at least 12 weeks.
  • Adequate organ function as determined by laboratory assessments.
  • Adequate cardiac ejection fraction as measured by echocardiogram.
  • Arm A-Japan and Arm D-Japan only: lives in Japan and is racially Japanese, defined as all biological grandparents being Japanese.

Arm A-China, Arm B-China, and Arm D-China only: is of Chinese descent and lives in China.

Arm D only: has been deemed suitable for assigned treatment based on assessment by the investigator.

Exclusion Criteria:

  • Prior anti-cancer treatment including investigational agents, immune checkpoint inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half-lives of the drug, whichever is shorter.
  • Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous anticancer treatment, including; greater than or equal to Grade 3 immune-mediated toxicity considered related to prior immunotherapy and that led to treatment discontinuation; or toxicity related to prior treatment that has not resolved.
  • Known additional malignancy that progressed or required active treatment within the last 2 years.
  • Uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years.
  • Concurrent medical condition requiring the use of systemic immunosuppressive treatment.
  • Cirrhosis or current unstable liver or biliary disease per investigator assessment.
  • Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
  • Prolonged QTas measured by electrocardiogram.
  • Allergen desensitization therapy within 4 weeks of starting study intervention.
  • History of hypersensitivity to any of the study interventions or their excipients.
  • History or evidence of significant cardiovascular (CV) risk.
  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
  • History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing pneumonia; noninfectious pneumonitis that required steroids, or evidence of active, noninfectious pneumonitis.
  • Pregnant or lactating woman.
  • Receipt of live vaccine within 30 days of the start of study intervention.
  • Receipt of transfusion of blood products or administration of colony-stimulating factors within 14 days before the first dose of study intervention.
  • Major surgery less than 4 weeks before the first dose of study intervention.
  • Known drug or alcohol abuse.

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): NCT04446351


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, California
GSK Investigational Site Recruiting
Los Angeles, California, United States, 90025
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Omid Hamid         
United States, Massachusetts
GSK Investigational Site Recruiting
Boston, Massachusetts, United States, 02215
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Stephen Hodi         
United States, Texas
GSK Investigational Site Recruiting
Dallas, Texas, United States, 75230
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: James Strauss         
GSK Investigational Site Recruiting
Houston, Texas, United States, 77030-4009
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jordi Rodón Ahnert         
GSK Investigational Site Recruiting
San Antonio, Texas, United States, 78229
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Drew W Rasco         
Canada, Ontario
GSK Investigational Site Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Scott A Laurie         
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Lillian Siu         
Japan
GSK Investigational Site Recruiting
Tokyo, Japan, 104-0045
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Noboru Yamamoto         
Korea, Republic of
GSK Investigational Site Recruiting
Seoul, Korea, Republic of, 03080
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Dong-Wan Kim         
GSK Investigational Site Recruiting
Seoul, Korea, Republic of, 06351
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Myung-Ju Ahn         
Sponsors and Collaborators
GlaxoSmithKline
23andMe, Inc.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04446351    
Other Study ID Numbers: 212214
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: November 24, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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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 GlaxoSmithKline:
GSK6097608
Dostarlimab
Dose escalation
Pharmacokinetics
Pharmacodynamics
Advanced solid tumors
First-time-in-human