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Phase 1 First Time in Human (FTIH), Open Label Study of GSK3745417 Administered to Participants With Advanced Solid Tumors

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03843359
Collaborator
(none)
300
Enrollment
11
Locations
2
Arms
74.3
Anticipated Duration (Months)
27.3
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of GSK3745417 administered alone (Part 1A) or co-administered (Part 2A) with dostarlimab in participants with refractory/relapsed solid tumors. Both parts will consist of a dose escalation phase.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
300 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
In Part 1A, escalating doses of GSK3745417 will be evaluated and in Part 2A, escalating doses of GSK3745417 in combination with dostarlimab will be evaluated as guided by the Bayesian Logistic Regression Model (BLRM). Part 1B (monotherapy dose expansion) & Part 2B (combination therapy dose expansion) will be planned upon conclusion of dose escalation parts.In Part 1A, escalating doses of GSK3745417 will be evaluated and in Part 2A, escalating doses of GSK3745417 in combination with dostarlimab will be evaluated as guided by the Bayesian Logistic Regression Model (BLRM). Part 1B (monotherapy dose expansion) & Part 2B (combination therapy dose expansion) will be planned upon conclusion of dose escalation parts.
Masking:
None (Open Label)
Masking Description:
This will be an Open-label study.
Primary Purpose:
Treatment
Official Title:
A Phase I First Time in Human Open Label Study of GSK3745417 Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors
Actual Study Start Date :
Mar 12, 2019
Anticipated Primary Completion Date :
Nov 18, 2024
Anticipated Study Completion Date :
May 22, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort

Drug: GSK3745417
GSK3745417 will be administered.
Experimental: Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort

Drug: GSK3745417
GSK3745417 will be administered.

Drug: Dostarlimab
Dostarlimab will be administered.

Outcome Measures

Primary Outcome Measures

  1. Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT) [Up to Day 29]

  2. Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity [Up to 2 years]

Secondary Outcome Measures

  1. Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone [Up to Week 104]

  2. Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone [Up to Week 104]

  3. Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone [Up to Week 104]

  4. Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone [Up to Week 104]

  5. Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab [Up to Week 104]

  6. Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab [Up to Week 104]

  7. Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab [Up to Week 104]

  8. Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab [Up to Week 104]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Participant must be more than or equal to (>=)18 years of age.

  • Participants with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.

  • Histological or cytological documentation of an advanced solid tumor.

  • Participants must provide a fresh biopsy.

  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

  • Adequate organ function per protocol specifications.

  • Male or female participants.

  • Female participants are eligible to participate if they are not breastfeeding or pregnant (or intend to breastfeed or become pregnant). Women of childbearing potential must use a highly effective method of contraception.

  • Capable of giving signed informed consent.

Exclusion Criteria:

  • 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 within 28 days before the first dose of study treatment.

  • Current unstable liver or biliary disease.

  • History of vasculitis at any time prior to study treatment.

  • Evidence or history of significant active bleeding or coagulation disorder.

  • Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C.

  • QT duration corrected for heart rate by Fridericia's formula (QTcF) more than (>)450 milliseconds (msec) or QTcF >480 msec for participants with bundle branch block.

  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.

  • Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.

  • History or evidence of cardiovascular (CV) risk

  • Recent (within the past 6 months) history of symptomatic pericarditis.

  • History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.

  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.

  • Prior treatment with the following agents:

  1. Stimulator of Interferon Genes (STING) agonist at any time.

  2. Anticancer therapy or investigational therapy or used an investigational device within 28 days or 5 half-lives of the drug, whichever is shorter.

  3. Checkpoint inhibitors, including Programmed death receptor-1 (PD-1), Programmed death Ligand-1 (PD-L1), PD-L2 and Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors within 28 days.

  4. Prior radiation therapy: permissible if at least 1 non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented.

  • Pregnant and/or breast feeding participants or those who plan to become pregnant and/or breastfeed.

  • Receipt of any live vaccine within 30 days of the start of study treatment.

  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.

  • Major surgery less than or equal to (<=)28 days before the first dose of study treatment. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.

  • Participants with signs/symptoms suggestive of Coronavirus Disease-2019 (COVID-19) within 14 days of study entry, or with known exposure to COVID-19 within 14 days prior to study entry.

  • Participants are excluded from Part 2A of the study if they have known hypersensitivity to dostarlimab or associated excipients.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Houston Texas United States 77030
2 GSK Investigational Site Melbourne Victoria Australia 3000
3 GSK Investigational Site Toronto Ontario Canada M5G 1Z9
4 GSK Investigational Site Bordeaux Cedex France 33076
5 GSK Investigational Site Villejuif cedex France 94805
6 GSK Investigational Site Seoul Korea, Republic of 03080
7 GSK Investigational Site Amsterdam Netherlands 1066 CX
8 GSK Investigational Site Amsterdam Netherlands 1081 HV
9 GSK Investigational Site Barcelona Spain 08035
10 GSK Investigational Site Madrid Spain 28040
11 GSK Investigational Site Madrid Spain 28050

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03843359
Other Study ID Numbers:
  • 208850
First Posted:
Feb 18, 2019
Last Update Posted:
Jun 22, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
GSK3745417
Dostarlimab
Anti-Programmed death receptor-1 (PD-1)
Monoclonal antibody
Solid tumor
First time in human
Stimulator of Interferon Genes
STING

Study Results

No Results Posted as of Jun 22, 2022