Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

CPI-0610

Open-label, sequential dose escalation and expansion study of CPI-0610 in patients with previously treated multiple myeloma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma

A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Previously Treated Multiple Myeloma

This outcome measure is a composite measure

Anti-myeloma activity will be assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma

The Leukemia and Lymphoma Society

Constellation Pharmaceuticals

Symptoms and General Pathology

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Lymphoma

Hematologic Neoplasms

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Lymphosarcoma

Acute Graft Versus Host Disease

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.

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.

After the MTD has been determined in Part1, Part 2 dose expansion cohorts will be opened for AML, NHL and MM.

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

GSK Clinical Trials

This is an open-label repeat dose, multicenter, 2-part study to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) for GSK525762 given once-daily (QD) orally. Part 1 of the study is a dose escalation phase to select the recommended Part 2 dose (RP2D) based on the safety, PK, and PD profiles observed after oral administration of GSK525762. Eligible subjects with select relapsed refractory hematological malignancies (acute myeloid leukemia \[AML\], non-Hodgkin's Lymphoma \[NHL\]and multiple myeloma \[MM\]), will be enrolled in the QD and/or BID dosing cohorts until a MTD is established. Subjects may continue treatment in the study until disease progression, unacceptable toxicity, or withdrawal of consent. . Upon determination of the MTD, twice daily (BID) dosing cohorts may be opened to collect additional safety data and evaluate the preliminary efficacy of GSK525762 administered BID. Part 2 will explore clinical activity at the MTD or RP2D; separate expansion cohorts will be planned for acute myeloid leukemia (AML), non-Hodgkin's Lymphoma (NHL, including an exploratory sub-cohort of subjects with myc and B-Cell Leukemia (BCL)2 and/or BCL6 rearrangements/overexpression \[double- and triple-hit lymphoma\]), and multiple myeloma (MM). This is the first study of this agent to be conducted in subjects with these relapsed and/or refractory hematological malignancies for which no standard therapies are anticipated to result in a durable remission.

A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies

A Phase I/II Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies

Time to Progression was planned to be analyzed.

Changes in QTcF and other safety parameters in relation to GSK525762 PK concentrations was planned to be analyzed.

Number of participants with dose /exposure markers related change in molecular markers (e.g. gene transcription and/or expression of proteins regulated by Bromodomain \[BRD\] proteins) in tumor tissue and/or peripheral blood samples were planned to be analyzed.

Plasma concentrations of GSK525762 in relationship with safety and efficacy parameters derived from PK/PD model was planned to be analyzed.

Number of participants with dose /exposure markers related change in molecular markers (e.g. gene transcription and/or expression of proteins regulated by Bromodomain proteins) in tumor tissue and/or peripheral blood samples were planned to be analyzed.

Overall survival (defined as the interval of time in months between the date of first dose and the date of death due to any cause) was planned to be analyzed.

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.

ORR is defined as the percentage of participants achieving stringent complete response (sCR), very good partial response (VGPR), partial response (PR) or minimal response (MR) for multiple myeloma (MM); CR or PR for Non-Hodgkin's Lymphoma (NHL); CR, CRp, CRi or PR for Acute Myeloid Leukemia (AML); CR, MR or PR for Myelodysplastic Syndrome (MDS) using the International Working Group (IWG) response criteria and IWG response criteria in myelodysplasia.

Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. AUC(0-24) represents AUC(0-tau) for repeat dose.

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.

Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis.

Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis.

Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. AUC(0-tau) is AUC(0-24) for repeat dose.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. PK parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.

The effects of treatment on disease-related symptoms/quality of life was assessed using the Skindex-29 Questionnaire, which inquires about how often (Never, Rarely, Sometimes, Often, All the time) during the previous 4 weeks the participant experienced the effect described in each of 29 items divided into 3 domains: Emotional (10 items), Symptoms (7 items) and Functioning (12 items). Responses to each item are transformed to a linear scale of 100, varying from 0 (no effect) to 100 (effect experienced all the time). Skindex-29 scores were reported as three individual domain scale scores; a scale score is the mean of a participant's responses to items in a given domain. Each domain score ranges from 0 (no effect) to 100 (effect experienced all the time), higher score implies higher impact of skin disease. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is defined is post-dose visit value minus Baseline.

Number of participants with any dose interruptions or delays is presented.

Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, Prothrombin international normalized ratio (Pro. INR), albumin, amylase, ALT, AST, bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, Triglycerides, 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.

Urine samples were collected to assess glucose, ketones, occult blood, urine protein. 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.

PFS defined as interval of time(in months) between date of first dose \& earlier of date of disease progression \& date of death due to any cause.Progression is participants(pt's)with MDS \& with \<5% blasts:\>=50% increase in blasts to\>5% blasts/pt's with 5-10% blasts:\>=50% increase to \>10% blasts, for pt's with 10-20% blasts:\>=50% increase to \>20% blasts,for pt's with 20%-30% blasts:\>=50% increase to \>30% blasts, for CTCL progression is \>=25% increase in skin disease from Baseline/new tumors (T3\[1 or more tumors(\>=1cm diameter\]) in pt's with T1(Limited patches,papules\&/or plaques covering \<10% of the skin surface;may further stratify into T1a \[patch only\] versus T1b \[plaque+-patch\]),T2(Patches,papules/plaques covering \>=10% of skin surface;may further stratify into T2a\[patch only\]versus T2b \[plaque+-patch\]) orT4(Confluence of erythema covering \>=80% body surface area) only skin disease/loss of response in those with CR/PR, increase of skin score of \> sum of nadir +50% Baseline score.

Duration of response is defined as the time from the first documented evidence response (CR or PR lasting 4 months for CTCL; and CR, marrow CR, CRp, Cri or PR for MDS) until the first documented disease progression or death due to any cause. Median and inter-quartile range (first quartile and third quartile) of duration of response are presented.

OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.

GlaxoSmithKline

All-cause mortality, non-serious AEs and SAEs were collected in All Treated population.

Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.

GSK525762 5 MG QD

Participants were administered once daily oral dose of 10 mg GSK525762.

GSK525762 10 MG QD

Participants were administered once daily oral dose of 20 mg GSK525762.

GSK525762 20 MG QD

Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.

GSK525762 30 MG QD MM

Participants were administered once daily oral dose of 40 mg GSK525762.

GSK525762 40 MG QD

Participants with MM were administered once daily oral dose of 40 mg GSK525762.

GSK525762 40 MG QD MM

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 40 mg GSK525762.

GSK525762 60 MG QD AML

Participants with Non-Hodgkin's Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.

GSK525762 60 MG QD NHL

Participants with MM were administered once daily oral dose of 60 mg GSK525762.

GSK525762 60 MG QD MM

Participants with AML were administered once daily oral dose of 75 mg GSK525762.

GSK525762 75 MG QD AML

Participants were administered once daily oral dose of 80 mg GSK525762.

GSK525762 80 MG QD

Participants with AML were administered once daily oral dose of 80 mg GSK525762.

GSK525762 80 MG QD AML

Participants with NHL were administered once daily oral dose of 80 mg GSK525762.

GSK525762 80 MG QD NHL

Participants with AML were administered once daily oral dose of 100 mg GSK525762.

GSK525762 100 MG QD AML

Participants with AML were administered once daily oral dose of 120 mg GSK525762.

GSK525762 120 MG QD AML

Participants Cutaneous T cell lymphoma (CTCL) were administered once daily oral dose of 60 mg GSK525762.

GSK525762 60 MG QD CTCL

Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762.

GSK525762 75 MG QD MDS

Participants CTCL were administered once daily oral dose of 80 mg GSK525762.

GSK525762 80 MG QD CTCL

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Part 2: GSK525762 60 mg QD CTCL

Part 2: GSK525762 75 mg QD MDS

Participants CTCL were administered once daily oral dose of 80 mg GSK525762

Part 2: GSK525762 80 mg QD CTCL

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

NA indicates, Data not presented due to participant confidentiality and privacy concerns

GSK Response Center

Non-serious AEs

SAEs

AELD

All Treated Population consists of all participants that received at least one dose of study treatment.

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD)

Participants with multiple myeloma were administered once daily oral dose of 40 mg GSK525762.

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Part 1: Number of Participants With Dose Reductions

Part 1: Number of Participants With Any Dose Interruptions or Delays

Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4

Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6

Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5

AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6

Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6

Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6

Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3

Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6

Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6

Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6

Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3

ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6

All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters

Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6

Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5

Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6

Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters

Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1

Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2

Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2

Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1

Monoclonal pro, n=0,0,0,0,0,1,0,0,2,0,0,0,0,0,0

Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method

Pulse rate, To Low

Pulse rate, To Normal or No change

Pulse Rate, To High

Temperature, To Low

Temperature, To Normal or No Change

Temperature, To High,

All Treated Population. Only those participants with data available at the specified data points were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma	NCT02157636	Multiple Myelom...	CPI-0610	18 Years -	Constellation Pharmaceuticals
A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies	NCT01943851	Neoplasms	GSK525762	18 Years -	GlaxoSmithKline
A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity of GSK525762 Plus Trametinib in Subjects With Solid Tumors	NCT03266159	Solid Tumours	GSK525762 Besyl... Trametinib tabl...	18 Years -	GlaxoSmithKline
Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer	NCT03936465	Solid Tumor, Ch... Lymphoma Brain Tumor, Pe...	BMS-986158 BMS-986378	1 Year - 21 Years	Dana-Farber Cancer Institute
A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma	NCT01949883	Lymphoma	CPI-0610	18 Years -	Constellation Pharmaceuticals
A Study of Absorption, Metabolism, and Elimination CC-90010 in Participants With Advanced Solid Tumors	NCT05678283	Advanced Solid ...	[14C]CC-90010 CC-90010	18 Years -	Bristol-Myers Squibb
ZEN003694 Combined With Niraparib in Patients With Metastatic or Recurrent Solid Tumors	NCT06161493	Ovarian Cancer Recurrent Solid...	ZEN003694 Niraparib	18 Years -	University of Pittsburgh
A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity of GSK525762 Plus Trametinib in Subjects With Solid Tumors	NCT03266159	Solid Tumours	GSK525762 Besyl... Trametinib tabl...	18 Years -	GlaxoSmithKline
A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma	NCT02157636	Multiple Myelom...	CPI-0610	18 Years -	Constellation Pharmaceuticals

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