Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK525762 · 3 trials · 3 indications
An AE is defined as 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 and SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. AELD is adverse events leading to permanent discontinuation of study treatment.
An event was considered DLT if it occurred within first 3weeks of treatment \& met one of following criteria:unless it was clearly established that event is unrelated to treatment:Grade4 neutropenia persisting for \>=7 days/febrile neutropenia not responding to treatment within 24hours, Grade4 thrombocytopenia lasting more than 7day \& not responding to transfusions/Grade3 thrombocytopenia associated with bleeding (\>10milliliter \[mL\]), Drug-related Grade 3/4 non-hematologic toxicity as described in National Cancer Institute-Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 4.0, Drug-related Grade2 non-hematological toxicity, Grade2 Troponin T elevation(central laboratory\>Upper Limit of Normal\[ULN\]),measured on two separate occasions within 48 hours, Treatment delay of 14 days/greater due to unresolved drug-related toxicity,ALT\>=3xULN+bilirubin\>=2xULN(\>35% direct)/Alanine aminotransferase(ALT) between 3-5xULN with bilirubin\<2xULN but with hepatitis symptom/rash/ALT\>=5xULN.
Number of participants with dose reductions due to any reason is presented.
Number of participants with any dose interruptions/ delays is presented.
Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, prothrombin international normalized ratio (Pro. INR), albumin, amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, triglycerides, alkaline phosphatase (ALP). 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. Higher grade indicates greater severity. An increase was defined as an increase relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.
Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. 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. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.
Urine samples were collected to assess glucose, ketones, occult blood, urine protein, and monoclonal protein (monoclonal pro). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented.
Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in the "To Normal or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date.
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Number of participants with increase to Grade 3 from Baseline is presented.
12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
ORR for MDS cohort is defined as the percentage of participants achieving Complete Response (CR), Marrow CR, CRp (as per CR but platelet count \<100 x 10\^9 cells/Liter\[L\]), CRi (as per CR but platelet count \<100 x 10\^9cells/L or neutrophil count \<1 x 10\^9 cells/L), or Partial Response (PR) per response criteria. Complete response is defined as bone marrow \<=5% myeloblasts with normal maturation of all cell lines, with hemoglobin concentration of \>=11 grams per deciliter (g/dL), absolute neutrophil count \>=1 x 10\^9 cells/L, platelet count \>=100x10\^9 cells/L and 0% blasts in the peripheral blood. Marrow CR is defined as Bone marrow \<=5% myeloblasts and decrease by \>=50% over pre-treatment. Objective response rate was determined by the investigator according to international myeloma working group (IMWG) response criteria.
ORR4 for CTCL cohorts is defined as the percentage of participants that have achieved a CR or PR lasting at least 4 months per global response criteria and the modified severity weighted assessment tool (mSWAT). ORR4 and 95% exact confidence interval is presented.
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; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment. All Treated Population comprised of all participants who received at least one dose of study treatment.
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; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment
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; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment.
The number of participants who had any dose reductions or delays is presented.
The number of participants who had any dose reductions or delays is presented.
The number of participants who had any dose reductions or delays is presented.
The number of participants who had any dose reductions or delays is presented.
Number of participants withdrawn due to toxicities is presented.
Number of participants withdrawn due to toxicities is presented.
Number of participants withdrawn due to toxicities is presented.
Number of participants withdrawn due to toxicities is presented.
Blood samples were collected for the analysis of: glucose, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin (Dir bil), bilirubin, N-Terminal proB-type natriuretic peptide (NT-BNP), calcium, cholesterol, creatine kinase (CK), chloride, carbon dioxide (CO2), creatinine, gamma glutamyl transferase (GGT), high and low density lipoprotein (HDL and LDL), insulin, potassium, lactate dehydrogenase (LDH), lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides, troponin I and T, urate and urea. Grading was done 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. Baseline is the most recent, non-missing value prior to or on first study treatment dose date. Data for worst case post-Baseline is presented.
Blood samples were collected for the analysis of clinical chemistry parameters: glucose, albumin, ALP, ALT, amylase, AST, Dir bil, bilirubin, NT-BNP, calcium, cholesterol, CK, chloride, CO2, creatinine, GGT, HDL and LDL cholesterol, insulin, potassium, LDH, lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides, troponin I and T, urate and urea. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post-Baseline is presented.
Blood samples were collected for the analysis of clinical chemistry parameters: glucose, albumin, ALP, ALT, amylase, AST, Dir bil, bilirubin, NT-BNP, calcium, cholesterol, CK, chloride, CO2, creatinine, GGT, HDL and LDL cholesterol, insulin, potassium, LDH, lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides (triglyc), troponin I and T, urate and urea. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post-Baseline is presented.
Blood samples were collected for the analysis of clinical chemistry parameters: glucose, albumin, ALP, ALT, amylase, AST, Dir bil, bilirubin, NT-BNP, calcium, cholesterol, CK, chloride, CO2, creatinine, GGT, HDL and LDL cholesterol, insulin, potassium, LDH, lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides, troponin I and T, urate and urea. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Blood samples were collected for the analysis of hematology parameters: activated partial thromboplastin time (aPTT), platelet count, red blood cell count (RBC), white blood cell count (WBC), prothrombin international normalized ratio (INR), prothrombin time (PT), fibrinogen (Fib), hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Blood samples were collected for the analysis of hematology parameters: aPTT, platelet count, RBC, WBC, INR, PT, Fib, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Blood samples were collected for the analysis of hematology parameters: aPTT, platelet count, RBC, WBC, INR, PT, Fib, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Blood samples were collected for the analysis of hematology parameters: aPTT, platelet count, RBC, WBC, INR, PT, Fib, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. 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. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Urine samples were collected for the analysis of following urine parameters: potential of hydrogen (pH), glucose, protein, occult blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented.
Urine samples were collected for the analysis of following urine parameters: pH, glucose, protein, occult blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented.
Urine samples were collected for the analysis of following urine parameters: pH, glucose, protein, blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented.
Urine samples were collected for the analysis of following urine parameters: pH, glucose, protein, occult blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented.
Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for pulse rate is \<60 beats per minute and \>100 beats per minute. Participants were counted twice if the participant "Decreased to \<60" and "Increased to \>100" post-baseline. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented
Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for pulse rate is \<60 beats per minute and \>100 beats per minute. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Participants were counted twice if the participant "Decreased to \<60" and "Increased to \>100" post-baseline.
Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for pulse rate is \<60 beats per minute and \>100 beats per minute. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (\<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (\>=160) and DBP: Grade 0 (\<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (\>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented
SBP and DBP were measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (\<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (\>=160) and DBP: Grade 0 (\<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (\>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented
SBP and DBP were measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (\<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (\>=160) and DBP: Grade 0 (\<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (\>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
SBP and DBP were measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (\<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (\>=160) and DBP: Grade 0 (\<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (\>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is \<=35 degree Celsius and \>=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is \<=35 degree Celsius and \>=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is \<=35 degree Celsius and \>=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is \<=35 degree Celsius and \>=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
Overall response rate is defined as the percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST version (v) 1.1). CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Overall response rate is defined as the percentage of participants who achieved a confirmed CR or PR from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Overall response rate is defined as the percentage of participants who achieved a confirmed CR or PR from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Overall response rate is defined as the percentage of participants who achieved a confirmed CR or PR from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
PSA 50 response rate is defined as the response rate that a PSA reduction from Baseline \>=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA \>=50% reduction is presented along with 95% confidence intervals.
PSA 50 Response rate is defined as the response rate that a PSA reduction from Baseline \>=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA \>=50% reduction is presented along with 95% confidence intervals.
PSA 50 response rate is defined as the response rate that a PSA reduction from Baseline \>=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA \>=50% reduction is presented along with 95% confidence intervals.
PSA 50 Response rate is defined as the response rate that a PSA reduction from Baseline \>=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA \>=50% reduction is presented along with 95% confidence intervals.
Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points. Besylate sub-study pharmacokinetic (PK) Parameter Population consisted of all participants in the PK Parameter Population who participated in the besylate substudy.
Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points.
Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points.
Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points.
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; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment
| Arm | Type | Description |
|---|---|---|
| Part 1: GSK525762 QD Cohort | EXPERIMENTAL | Subject will be administered a 5 milligram (mg) starting dose of GSK525762, oral tablets, QD. Dose escalations will be performed in Part 1 and dose adjustments are allowed to address tolerability and safety issues. Thereafter, subjects will be enrolled in a standard 3+3 design. Separate dose escalation cohorts will be opened for subjects with AML, NHL, and MM for QD dosing. Dose escalation will continue until an MTD is determined or until a dose of 200 mg per day is reached. |
| Part 1: GSK525762 BID Cohort | EXPERIMENTAL | Subject will be administered a starting dose of GSK525762, oral tablets, 20 mg BID (12 hours apart, total daily dose of 40 mg). Dose escalations will be performed in Part 1 and dose adjustments are allowed to address tolerability and safety issues. Thereafter, subjects will be enrolled in a standard 3+3 design. Separate dose escalation cohorts will be opened for subjects with AML, NHL, and MM, for BID dosing. Dose escalation will continue until an MTD is determined or until a dose of 200 mg per day is reached. |
| Part 2: GSK525762 dose expansion cohort | EXPERIMENTAL | After the MTD has been determined in Part1, Part 2 dose expansion cohorts will be opened for AML, NHL and MM. |
| Part 1 Cohort 1 | EXPERIMENTAL | Subjects will receive a single dose of GSK525762 10 mg on Day 1 followed by 200 mg Itraconazole two times a day (BID) on Day 3. On Day 4 to Day 6 inclusive subjects will receive a single dose of itraconazole 200 mg in the morning. On Day 7 subjects will receive a single dose of GSK525762 5 mg one hour after receiving 200 mg dose of itraconazole. On day 8 and 9 subjects will receive a single dose of 200 mg itraconazole in the morning. |
| Part 1 Cohort 2 | EXPERIMENTAL | Subjects will receive a single dose of GSK525762 10 mg on day 1 followed by 200 mg Itraconazole BID on day 3. On day 4 to day 6 inclusive subjects will receive a single dose of itraconazole 200 mg in the morning. On day 7 subjects will receive a single dose of GSK525762 5 mg or GSK525762 10 mg one hour after receiving 200 mg dose of itraconazole. On day 8 and 9 subjects will receive a single dose of 200 mg itraconazole in the morning. |
| Part 2 | EXPERIMENTAL | Subjects will receive a single dose of GSK525762 10 mg on day 1. From day 3 to 17 inclusive, subjects will receive a single dose of 600 mg rifampicin in fasting conditions. On day 18 subjects will receive single dose of GSK525762 either 20 or 30 mg along with 600 mg dose of rifampicin. On day 19 subjects will receive a single dose of rifampicin 600 mg. |
| Single and Repeat Dose finding cohort | EXPERIMENTAL | All subjects will follow a 3+3 dose escalation design for GSK525762 and the dose will be escalated based on all available data, including PK data and the safety profile of prior cohorts, as well as the recommended dose from the Neuenschwander- Continuous Reassessment Method (N-CRM) design. |
| Expansion Cohort | EXPERIMENTAL | Up to 150 additional subjects with NMC and other solid tumors may be enrolled in expansion cohorts. The recommended Phase 2 (Part 2) dose (RP2D) of GSK525762 will be determined based on the MTD or biologically active dose (example: clinical response), the safety profile and available pharmacodynamic data generated from all subjects in Parts 1 |
| Besylate Sub study | EXPERIMENTAL | Tablet and amorphous tablet in one of the two sequences (ABCD or BACD). Where Treatment A: RP2D/MTD as amorphous free-base tablet + low dose stable isotope in solution, fasted Treatment B: RP2D/MTD as besylate tablet + low dose stable isotope in solution, fasted. Treatment C: half to one-third of RP2D/MTD as besylate tablet + low dose stable isotope in solution, fasted. Treatment D: RP2D/MTD as besylate tablet, fed |
| Name | Type | Description |
|---|---|---|
| GSK525762 | DRUG | GSK525762 1 mg, 10 mg and 30 mg will be supplied as white to off-white, amorphous free base and white to slightly colored crystalline besylate tablets, round, biconvex tablets with no markings. GSK525762 will be administered with 240 milliliter (mL) water. |
| GSK525762 Besylate Tablets | DRUG | GSK525762 is available as a film-coated, white to slightly colored round, biconvex tablets with no markings. It is available in unit dose strength of 5 mg. |
| Itraconazole 200 mg | DRUG | Itraconazole is available as a clear yellow solution with unit dose strength of 10 mg/mL |
| Rifampicin 300 mg | DRUG | Rifampicin is available as a red capsule with printed markings and as a 300 mg unit dose strength. |
Inclusion criteria * Written informed consent provided. * Males and females 18 years old or older. * In Part 1 and, Part 2, subjects must have AML, MM, or NHL. Subjects with AML, are eligible if they • have relapsed and/or refractory disease, OR are\>=65 years of age and not candidates for or have ...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 5 | PHASE3 | ACE-536 |
| AbbVie, Inc. | ABBV | 4 | PHASE3 | Navitoclax, Ruxolitinib |
| Novartis AG Sponsored ADR | NVS | 3 | PHASE3 | Pelabresib, Ruxolitinib |
| Karyopharm Therapeutics, Inc. | KPTI | 4 | PHASE3 | Selinexor, Ruxolitinib |
| Geron Corporation | GERN | 2 | PHASE3 | Imetelstat |
| Merck & Co., Inc. | MRK | 1 | PHASE3 | Bomedemstat |
| Incyte Corporation | INCY | 10 | PHASE2 | Ruxolitinib |
| GSK plc Sponsored ADR | GSK | 2 | PHASE2 | MMB |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 1 | PHASE2 | Elritercept, Ruxolitinib |
| Eli Lilly and Company | LLY | 1 | PHASE1 | LY3410738, Venetoclax, Azacitidine |
| Disc Medicine, Inc. | IRON | 1 | PHASE1 | DISC-0974 |
| Galecto, Inc. | GLTO | 1 | PHASE2 | GB2064 |
| Prelude Therapeutics, Inc. | PRLD | 1 | PHASE1 | PRT12396 |
| United Therapeutics Corporation | UTHR | 1 | PHASE2 | bomedemstat |
GSK525762 is an investigational small molecule being studied for the treatment of NUT midline carcinoma (NMC) and other cancers, including relapsed or refractory hematologic malignancies. It has also been evaluated in healthy volunteers for drug interaction studies. GSK525762 is in clinical development and is not approved by the FDA.
GSK525762 is a small molecule developed by GSK plc. The specific molecular target of GSK525762 is not disclosed in the available information. Clinical trials have investigated its safety, pharmacokinetics, pharmacodynamics, and clinical activity in patients with NUT midline carcinoma and other cancers.
GSK525762 is developed by GSK plc, a global biopharmaceutical company listed on the London Stock Exchange under the ticker GSK. The drug is an investigational small molecule in Phase 1 and Phase 2 clinical trials for oncology indications, including NUT midline carcinoma and hematologic malignancies.
GSK525762 is in clinical development, with trials conducted in Phase 1 and Phase 2. One Phase 1 study in NUT midline carcinoma and other cancers is completed, as is a Phase 2 study in relapsed or refractory hematologic malignancies. The drug is investigational and not FDA approved.
GSK525762 has been studied in three completed clinical trials: NCT01587703, a Phase 1 study in NUT midline carcinoma and other cancers with 196 participants; NCT01943851, a Phase 2 study in relapsed or refractory hematologic malignancies with 111 participants; and NCT02706535, a Phase 1 drug interaction study in healthy female subjects.
GSK525762 is also known by the name molibresib. The drug is an investigational small molecule developed by GSK plc for the treatment of NUT midline carcinoma and other cancers. It has been evaluated in clinical trials for safety, pharmacokinetics, and clinical activity.