Clinical trial NCT03843359: A First Time in Human (FTIH) Study of GSK3745417 Administered to Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Keywords: GSK3745417
Dostarlimab
Anti-Programmed death receptor-1 (PD-1)
Monoclonal antibody
Solid tumor
First time in human
Stimulator of Interferon Genes
STING
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-02-18
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT)
timeFrame: Up to Day 29
measure: Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity
timeFrame: Up to 2 years
Secondary outcomes:
measure: Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone
timeFrame: Up to Week 104
measure: Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone
timeFrame: Up to Week 104
measure: Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone
timeFrame: Up to Week 104
measure: Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone
timeFrame: Up to Week 104
measure: Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab
timeFrame: Up to Week 104
measure: Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab
timeFrame: Up to Week 104
measure: Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab
timeFrame: Up to Week 104
measure: Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab
timeFrame: Up to Week 104
Other outcomes:
Locations:
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Melbourne
country: Australia
facility: GSK Investigational Site
city: Toronto
country: Canada
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Villejuif cedex
country: France
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: