Last updated: 09/06/2021 12:40:10

Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects with Advanced Her3-Positive Solid Tumors

Request patient level data
GSK study ID
117158
See study documents
Clinicaltrials.gov ID
NCT01966445
See results summary
EudraCT ID
2013-001699-39
EU CT Number
Not applicable
Trial status
Completed
Completed
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I, First Time in Human, Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Anti-Her3 Monoclonal Antibody GSK2849330 in Subjects with Advanced Her3-Positive Solid Tumors
Trial description: Human Epidermal Growth Factor Receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody targeting HER3, is a new agent for subjects whose tumors express HER3. This study is a phase I, first time in human, open-label, dose escalation study. The purpose of this study is to investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849330 in subjects with advanced HER3-positive solid tumors. The study will be conducted in two parts. Part 1 (Dose-Escalation Phase) will include dose escalation and PK/PD cohorts to evaluate safety, PK, and PD to guide selection of dose regimen(s) for Part 2. In Part 2 (Expansion Cohorts), up to 3 cohorts will be enrolled at the dose regimen(s) selected based on Part 1 data, to evaluate safety in a larger cohort of subjects at the recommended dose regimen and also to evaluate preliminary evidence of clinical benefit.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Number of participants with dose-limiting toxicities (DLTs)-Parts 1 and 2

Timeframe: Up to 28 days

Number of participants with grade change from Baseline in clinical chemistry data-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in clinical chemistry data with respect to normal range-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with grade change from Baseline in hematology data-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in hematology data with respect to normal range-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in urinalysis data with respect to normal range-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in vital signs-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with abnormal electrocardiogram (ECG) findings-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Secondary outcomes:

Maximum observed plasma concentration (Cmax) of GSK2849330-Part 1

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Cmax of GSK2849330-Part 2

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Time of occurrence of Cmax (Tmax) for GSK2849330-Part 1

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Tmax for GSK2849330-Part 2

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Area under the concentration time curve (AUC) to a fixed nominal time (AUC[0 to 168]) and AUC(0 to 336) for GSK2849330-Part 1

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

AUC(0 to 168) and AUC(0 to 336) for GSK2849330-Part 2

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Serum HER3 from tumor tissue-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Overall response rate (ORR)-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Number of participants with antibodies to GSK2849330 in serum

Timeframe: Median of 6.143 weeks of drug exposure

Percentage of cluster of differentiation (CD) marker

Timeframe: Median of 6.143 weeks of drug exposure

Interventions:
Biological/vaccine: GSK2849330
Enrollment:
29
Observational study model:
Not applicable
Primary completion date:
2017-18-09
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Cancer, Neoplasms
Product
GSK2849330
Collaborators
Not applicable
Study date(s)
November 2013 to September 2017
Type
Interventional
Phase
1

Participation criteria

Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
  • Males and females >=18 years of age (at the time consent is obtained).
  • Written informed consent provided.
  • Subjects with leptomeningeal or brain metastases or spinal cord compression.
  • Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
Inclusion and exclusion criteria
Inclusion criteria:
  • Males and females >=18 years of age (at the time consent is obtained).
  • Written informed consent provided.
  • Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
  • Sufficient archival tumor specimen is available for HER3 immunohistochemistry (IHC) analysis, or subject is willing to undergo a fresh tumor biopsy for HER3 IHC analysis.
  • Histologically or cytologically confirmed diagnosis of one of the following solid tumor malignancies for which no standard therapeutic alternatives exist: bladder cancer, breast cancer, castrate-resistant prostate cancer, cervical cancer, colorectal cancer (CRC), gastric cancer, hepatocellular carcinoma (HCC), melanoma, non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, squamous cancers of the head and neck region (including parotid and nasopharynx).
Exclusion criteria:
  • Subjects with leptomeningeal or brain metastases or spinal cord compression.
  • Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
  • Concurrent medical condition that would jeopardize compliance.
  • Receiving chronic immunosuppressive therapies (includes daily steroid doses in excess of 20 milligrams [mg]/day of prednisone).

Trial location(s)

Location
Status
Contact us
Contact us
Location
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
Status
Study Complete
Contact us
Location
GSK Investigational Site
GRONINGEN, Netherlands, 9713 GZ
Status
Study Complete
Contact us
Location
GSK Investigational Site
Heidelberg, Victoria, Australia, 3084
Status
Study Complete
Contact us
Location
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Status
Study Complete
Contact us
Location
GSK Investigational Site
NIJMEGEN, Netherlands, 6525 GA
Status
Study Complete
Contact us
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Contact us
Location
GSK Investigational Site
New York, New York, United States, 10065
Status
Study Complete
Contact us
Location
GSK Investigational Site
ROTTERDAM, Netherlands, 3075 EA
Status
Study Complete
Contact us
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84112
Status
Study Complete
Contact us

Study documents

Clinical study report
Available language(s): English
Download document(s)
Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Completed
Actual primary completion date
2017-18-09
Actual study completion date
2017-18-09

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website