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GSK2849330

Phase 1

Cancer | Small molecule | Oncology |GSK plc|Last Updated: Jul 1, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials2
Total Enrollment35
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02345174Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid TumorsPHASE1 COMPLETED 6Mar 19, 2015Jun 2, 2016Feb 21, 20192 Netherlands
NCT01966445Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid TumorsPHASE1 COMPLETED 29Nov 26, 2013Sep 18, 2017Jul 1, 201914 United States, Australia +1
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Study Endpoints
Primary Endpoints
Standardized Uptake Value (SUV).
Up to Day 21

Regions of interest (RoI) will be outlined from PET-CT images to represent the tissue radioactivity concentration through the values of SUVmean and SUVpeak.

Volume of region of interest.
Up to Day 21

RoIs will be outlined to represent whole organs and include the volumes encircled

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Parts 1 and 2
Median of 6.143 weeks of drug exposure

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the outcomes mentioned; events of possible study treatment-induced liver injury with hyperbilirubinemia; and left ventricular ejection fraction (LVEF) meeting stopping criteria. AEs were collected in All Treated Population which comprised of all participants who received at least one dose of GSK2849330. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Dose-limiting Toxicities (DLTs)-Parts 1 and 2
Up to 28 days

An event was considered a DLT if it occured within the first 4 weeks (28 days) of treatment, and met one of the following criteria unless it could be established that the event was unrelated to treatment: Grade 3 or greater non-hematologic toxicity; Grade 4 neutropenia lasting \>5 days; Febrile neutropenia, of any grade or duration; Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with bleeding; Alanine aminotransferase (ALT) \>3 times upper limit of normal (ULN) with bilirubin \>2 times ULN; Any Grade 2 or greater toxicity that in the judgment of the investigator and GlaxoSmithKline (GSK) Medical Monitor, would be considered dose-limiting; Grade 3 or greater decrease in LVEF. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Parts 1 and 2
Baseline and median of 6.143 weeks of drug exposure

Blood samples were collected for the analysis of following clinical chemistry parameters: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Total bil), calcium, creatinine, gamma glutamyl transferase (GGT), glucose, potassium, magnesium, sodium, phosphorus, uric acid. Laboratory parameters were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. Data for worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Parts 1 and 2
Baseline and median of 6.143 weeks of drug exposure

Blood samples were collected for the analysis of following clinical chemistry parameters: direct bilirubin (D.Bil.), cancer antigen (CA)-125, CA-15.3, CA19-9, chloride, carbon dioxide (CO2)/bicarbonate (HCO3), luteinizing hormone (LH), total protein and urea or blood urea nitrogen (BUN). Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Number of participants with change from Baseline in clinical chemistry data at worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Grade Change From Baseline in Hematology Data-Parts 1 and 2
Baseline and median of 6.143 weeks of drug exposure

Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, total neutrophils, platelet count, and white blood cell (WBC). The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. Number of participants with any grade increase, increase to Grade 3 and increase to Grade 4 in hematology data at worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Parts 1 and 2
Baseline and median of 6.143 weeks of drug exposure

Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, hematocrit, mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV), monocytes, red blood cell count (RBC) and reticulocytes. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as value at visit minus Baseline value. Number of participants with change from Baseline in hematology data at worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Change From Baseline in Urinalysis Data With Respect to Normal Range-Parts 1 and 2
Baseline and median of 6.143 weeks of drug exposure

Urine samples were collected for the analysis of urine potential of hydrogen (pH) and urine specific gravity. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. The data for worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Number of Participants With Change From Baseline in Vital Signs-Parts 1 and 2
Baseline and median of 6.143 weeks of drug exposure

Vital sign measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature (Temp) and heart rate (HR). Vital signs were graded according to NCI-CTCAE version 4.0. The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in HR (decrease to \<60 beats per minute and increase to \>100 beats per minute); increase in SBP from Baseline (\>=120 to \<140 millimeters of mercury \[mmHg\] Grade 1; \>=140 to \<160 mmHg \[Grade 2\]; \>=160 \[Grade 3\]); increase in DBP from Baseline (\>=80 to \<90 \[Grade 1\]; \>=90 to \<100 \[Grade 2\]; \>=100 mmHg \[Grade 3\]) and change in temperature from Baseline (increase to \>=38 or decrease to \<=35 degree Centigrade). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. The data for worst-case post Baseline is presented.

Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Parts 1 and 2
Median of 6.143 weeks of drug exposure

A 12-lead ECG was measured using an automated ECG machine after at least 5 minutes of rest for the participant in a semi-recumbent or supine position. Number of participants with abnormal ECG findings at any time post-Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Secondary Endpoints
Anatomical localization of radiolabel.
Up to Day 21
Uptake of-GSK2849330 in tumors using pharmacometric model
Up to Day 21
Change in uptake parameters in response to the dose difference between dose 1 and 2.
Up to Day 21
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeOTHER
Treatment Arms
ArmTypeDescription
Imaging Phase + Continuation PhaseEXPERIMENTALIn Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.
GSK2849330 Part 1EXPERIMENTAL1 hour infusion administered intravenously at intervals of one week or more (escalating doses).
GSK2849330 Part 2EXPERIMENTALIntravenous infusion administered at the dose and schedule established in Part 1
Interventions
NameTypeDescription
GSK2849330DRUGGSK2849330 solution (100 mg/mL) for infusion diluted in 0.9% sodium chloride to the appropriate concentration for the dose.
89Zr-GSK2849330DRUG89Zr-GSK2849330 solution for intravenous administration diluted with GSK2849330 Solution for Infusion (unlabelled GSK2849330) with a target radioactivity of 37MBq and a total antibody concentration of 0.4 mg/mL or 1.2 mg/mL.
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites2

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 immunoh...

Countries:NetherlandsUnited StatesAustralia
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