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GSK3052230

Phase 1

Neoplasms | Small molecule | Oncology |GSK plc|Last Updated: Aug 19, 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 Trials1
Total Enrollment65
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01868022Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway SignalingPHASE1 COMPLETED 65Oct 9, 2013Oct 24, 2017Aug 19, 201929 United States, Belgium +5
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Study Endpoints
Primary Endpoints
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
Median of 28.5 weeks

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, protocol-specific events including drug-induced liver injury with hyperbilirubinaemia, any new primary cancers, cardiac toxicity including Left Ventricular Ejection Fraction (LVEF) changes or treatment emergent cardiac valve toxicity and treatment emergent acute anterior uveitis were categorized as SAE. Participants having non-serious AE or SAE were included in the analysis. The All Treated Subjects Population comprised of all participants who received at least one dose of study treatment.

Number of Participants With Severe AEs and SAEs
Median of 28.5 weeks

The severity of AEs were graded utilizing National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.3. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or noninvasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life-threatening consequences; urgent intervention indicated. Grade 5 represents death related to AE.

Number of Participants Withdrew Due to AEs
Median of 28.5 weeks

An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The AEs leading to permanent discontinuation from the study has been reported.

Number of Participants With Dose Reduction
Median of 28.5 weeks

Dose reduction and delays were done due to toxicity, or in the interest of participant's safety per investigator discretion. Requirement for more than 2 dose reductions resulted in permanent discontinuation of chemotherapy. Participants with dose reduction has been reported.

Number of Participants With Dose Delays
Median of 28.5 weeks

Dose reduction and delays were done due to toxicity, or in the interest of participant's safety per investigator discretion. Requirement for more than 2 dose reductions resulted in permanent discontinuation of chemotherapy. Participants with dose delay has been reported.

Treatment Duration With GSK3052230
Median of 28.5 weeks

The number of participants administered study treatment were summarized according to the duration of therapy. The extent of treatment exposure is calculated as the number of cycles administered. The duration of exposure to study treatment is calculated from first day to last day of treatment plus 1 day. Median and full range (minimum and maximum) has been reported.

Number of Participants With Dose-Limiting Toxicities (DLT)
Median of 28.5 weeks

DLT is defined as toxicities due to GSK3052230 or due to the combination of GSK3052230 with chemotherapy within Cycle 1 (first 21 days of period on study) that are unlikely to be due to another cause, such as the known effects of cytotoxics chemotherapy alone, disease progression, or accident, and protocol-specified criteria. Clinically significant toxicities that persist or occur beyond Cycle 1 that the investigator and GlaxoSmithKline (GSK) medical monitor consider dose-limiting may also be designated a DLT for the purpose of establishing Maximum tolerated dose (MTD). Number of participants with DLTs has been reported.

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Baseline and up to Median of 28.5 weeks

Blood pressure was measured in a semi-supine position after 5 minutes of rest. Blood pressure was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented. NA indicates that data were not available as standard deviation could not be calculated for a single participant. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Heart Rate
Baseline and up to Median of 28.5 weeks

Heart rate was measured in a semi-supine position after 5 minutes of rest. Heart rate was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented.

Change From Baseline in Temperature
Baseline and up to Median of 28.5 weeks

Temperature was measured in a semi-supine position after 5 minutes of rest. Temperature was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented.

Number of Participants With Clinically Significant Findings for 12-lead Electrocardiogram (ECG)
Median of 28.5 weeks

A single 12-lead ECG was performed at the specified timepoints during the study where the participant was instructed to be in semi-recumbent position for 5 minutes before obtaining the ECG. An ECG machine that automatically calculated the heart rate and measures like the PR, QRS, QT, and corrected QT intervals. Number of participants with worst-case post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported.

Number of Participants With Abnormal Echocardiogram (ECHO) Findings
Median of 28.5 weeks

Echocardiography scans were obtained at given time points using an echocardiogram and the findings for left ventricular ejection fraction (LVEF) were obtained. LVEF values at end of treatment (EOT) were recorded as no change or any increase and any decrease values. Only those participants available at the specified time points were analyzed.

Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range
Median of 28.5 weeks

Clinical chemistry parameters included potassium, sodium, chloride (Cl), total carbon dioxide (CO2), total and ionized calcium, magnesium, phosphate, albumin, glucose (fasting), Blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, Total bilirubin (T. Bil), and Direct bilirubin (D. Bil), total T3 and T4, free T4, amylase, lipase, prothrombin time, partial thromboplastin time, international normalized ratio, and fibrinogen. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Clinical chemistry parameters with change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Number of Participants With the Abnormal Urinalysis Findings
Up to Cycle 16 (each cycle was of 21 days)

Urinalysis parameters included urine protein, urine glucose, urine ketones and occult blood were assessed. Dipstick test was performed for routine urinalysis. Abnormal values such as trace, 1+, 2+, 3+, 4+, \>1000, \>=1000, and \>10 have been reported.

Number of Participants With Hematology Change From Baseline With Respect to the Normal Range
Median of 28.5 weeks

Hematology parameters included platelet Count, red blood cell (RBC) Count, hemoglobin, absolute white blood cell (WBC) Count, absolute neutrophils (Neu), absolute lymphocytes (Lym), absolute monocytes (Mono), absolute eosinophils (Eos), absolute basophils (Baso). Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Hematology parameters with worst-case change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Number of Participants With Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD)
Median of 28.5 weeks

The MTD is defined as the highest dose level tested at which \< 33 percent of participants experience a DLT. In cases when MTD is not reached dose was described as the MFD.

Number of Participants With Best Response
Median of 28.5 weeks

Best response defined as complete response (CR:disappearance of all target. Any pathological lymph nodes \< 10 millimeter \[mm\] in the short axis) or partial response (PR at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters), stable disease (SD neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) or progressive disease (PR at least a 20 percent increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST. Best response as per RECIST version 1.1 for Arm A and B participants has been reported. Best response according to RECIST version 1.1 or modified RECIST for Arm C participants has been reported.

Number of Participants With Overall Response Rate (ORR)
Median of 28.5 weeks

Overall Response Rate (ORR) is defined as the percentage of participants achieving a confirmed Complete response (CR) or Partial response (PR) from the start of treatment until disease progression as per RECIST version 1.1 or modified RECIST for participants in Arm C. This was determined based on Investigator assessments of response. 95% confidence intervals (CI) are calculated based on the unconditional exact method. ORR as per RECIST vesrion 1.1 for Arm A and B has been reported. ORR as per RECIST version 1.1 and modified RECIST version 1.1 for Arm C has been reported. The study population used for decision-making at the interim analyses during the dose expansion cohorts of the study arms is termed as the All Evaluable Participants Population. NA indicates 0 participants met ORR criteria therefore no dispersion.

Secondary Endpoints
Progression Free Survival (PFS) as Assessed by Investigator
Median of 28.5 weeks
Clearance of GSK3052230
Cycle(C)1 Day (D) 1 Pre-dose, End of infusion, 1 and 2 hours post-dose;C1 D8 Pre-dose,end of infusion; C2 D1 Pre-dose, End of infusion, 1 and 2 hours post-dose;C4 D1 Predose, end of infusion;C6 D1 Pre-dose, end of infusion,C12 D1 Pre-dose, end of infusion
Volume of Distribution of GSK3052230
Cycle(C)1 Day (D) 1 Pre-dose, End of infusion, 1 and 2 hours post-dose;C1 D8 Pre-dose,end of infusion; C2 D1 Pre-dose, End of infusion, 1 and 2 hours post-dose;C4 D1 Predose, end of infusion;C6 D1 Pre-dose, end of infusion,C12 D1 Pre-dose, end of infusion
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Arm A: GSK3052230 + paclitaxel/carboplatinEXPERIMENTALSubject will receive GSK3052230 as 30-minute intravenous (i.v.) infusion once a week (Day 1, Day 8, Day 15) of each 21-day cycle + paclitaxel (constant infusion for 3 hrs) and carboplatin (constant infusion for 30 to 60 minutes) iv on Day 1 of each 21-day cycle. The number of cycles of paclitaxel/carboplatin will be limited to 4 to 6 cycles.
Arm B: GSK3052230 + docetaxelEXPERIMENTALSubject will receive GSK3052230 as 30-minute intravenous (i.v.) infusion once a week (Day 1, Day 8, Day 15) of each 21-day cycle + docetaxel as 1 hour iv infusion on Day 1 of each 21-day cycle. Subjects may continue to receive docetaxel until disease progression or as long as they are considered to derive benefit from treatment.
Arm C: GSK3052230 + pemetrexed and cisplatinEXPERIMENTALSubject will receive GSK3052230 as 30 minute iv infusion once a week (Day 1, Day 8, Day 15) of each 21 day cycle + pemetrexed iv infusion over 10 minutes on Day 1 of each 21 day cycle followed 30 minutes later by iv Cisplatin infused over 2 hours
Interventions
NameTypeDescription
GSK3052230DRUGA clear to opalescent, colorless to pale yellow solution for IV infusion once weekly (Day 1, Day 8, Day 15) in each 21-day cycle with unit dose strengths/dose level of 5, 10, 15, and 20 mg/kg supplied in a sterile 25 mL glass vial.
paclitaxelDRUGpaclitaxel will be from commercial stock.
carboplatinDRUGcarboplatin will be from commercial stock.
docetaxelDRUGdocetaxel will be from commercial stock.
pemetrexedDRUGpemetrexed will be from commercial stock
cisplatinDRUGcisplatin will be from commercial stock
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites29

Inclusion Criteria * Signed written informed consent * Histologically or cytologically confirmed diagnosis: Arm A and B- stage IV recurrent metastatic squamous NSCLC with Fibroblast growth factor receptor 1 (FGFR1) gene amplification by central laboratory testing. Arm C- recurrent after local thera...

Countries:United StatesBelgiumDenmarkNetherlandsRussiaSpainUnited Kingdom
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