Solid Tumors
Conditions
Keywords
cancer, tumors, PARP
Brief summary
CEP-9722 is an inhibitor of poly-adenosine diphosphate (ADP) ribose polymerase -1 and -2 (PARP). The primary purpose of this study is to (Part 1) determine the maximum tolerated dose (MTD) of CEP-9722 administered daily to participants with advanced or metastatic solid tumors, (Part 2) to evaluate the safety and tolerability of that dose, and to investigate whether CEP-9722 has antitumor activity as a single agent.
Interventions
DRUGCEP-9722
CEP-9722 will be administered per dose and schedule specified in the arm description.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant has histologically confirmed, locally advanced or metastatic solid tumor considered incurable and unresponsive to standard therapies. * The participant has disease progression following at least 1 prior standard chemotherapy regimen. * The participant is a man or woman at least 18 years of age. * The participant has a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * The participant has a life expectancy of 12 weeks or more. * The participant has adequate hematologic function as evidenced by: * absolute neutrophil cell (ANC) count 1.5 x10\^9/liter (L) or more * hemoglobin 10 grams (g)/deciliter (dL) or more * platelets 100 x 10\^9/L or more * The participant has adequate hepatic function as evidenced by: * total bilirubin 1.5 times the upper limit of normal (ULN) or less, unless secondary to Gilbert's disease (any Gilbert's disease must be documented, and bilirubin must be 3 times the ULN or less.) * alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase of 2.5 times ULN or less * The participant has adequate renal function as defined by creatinine of less than 1.5 times ULN or less. * The participant must take precautions to not become pregnant or produce offspring. Women must be of non-childbearing potential (surgically sterile or postmenopausal for at least 12 months, confirmed by follicle-stimulating hormone \[FSH\] \>40 IU/L) or agree to use a medically accepted method of contraception for the duration of the study and 90 days after treatment. Men must be surgically sterile or agree to use a medically accepted method of contraception for the duration of the study and 90 days after treatment. Acceptable methods of contraception include abstinence, barrier method with spermicide (excluding cervical cap and sponge), intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. * Written informed consent is obtained. * In Part 2: In addition to the criteria above, participants should have documented deficiencies of DNA repair pathways, such as BRCA1/2, or have prostate, breast, or gastric cancer and ability to provide fresh or archived tumor specimens.
Exclusion criteria
* Other than malignancy, the participant has any serious or uncontrolled surgical, medical, or psychiatric history that could pose an unacceptable health risk to the participant, prevent compliance with study procedures, or compromise the study integrity, including, but not limited to the following: 1. recent history of cardiac ischemic disease (acute myocardial infarction within 6 months, unstable angina) 2. cardiac arrhythmia that is uncontrolled or that requires medication 3. recent transient ischemic attack or stroke (within 6 months) or residual dysfunction from stroke 4. history of seizure disorder (part 1 only) 5. clinically significant pulmonary disease (eg, fibrosis on chest x-ray or significant dyspnea as assessed by investigator) 6. poorly controlled hypertension (systolic \>140 millimeters of mercury (mm Hg) or diastolic \>90 mm Hg) 7. uncontrolled active infection within the past 7 days 8. poorly controlled diabetes mellitus as assessed by investigator 9. recent major surgery (within 4 weeks prior to study day 1) or minor surgery (within 2 weeks prior to study day 1) * The participant has previously received a PARP inhibitor. * The participant has received antitumor therapy or other investigational agent within 4 weeks (with the exception of LHRH therapy in participants with prostate cancer) or nitrosourea therapy within 6 weeks. * The participant has clinically symptomatic brain metastases or required treatment for brain metastases within 4 weeks (stable sequelae acceptable if treatment has been completed). * The participant has residual adverse events of greater than grade 1 severity from prior radiotherapy or chemotherapy agents. * The participant has known immunodeficiency virus (HIV) infection, acute or chronic hepatitis B infection,or hepatitis C infection. * The participant is a pregnant or breast-feeding woman. (Any women becoming pregnant during the study will be withdrawn from the study.) * The participant has medical or surgical gastrointestinal history that would interfere with the absorption of study drug. * The participant requires treatment with a proton pump inhibitor or H2 antagonist or has taken a proton pump inhibitor or H2 antagonist within 4 days before CEP-9722 administration. * The participant has risk factors for Torsades de Pointes as follows: * history of Long QT syndrome or unexplained syncope * history of congestive heart failure (New York Heart Association class III or IV) * concomitant treatment with medication known to prolong QT/QTc interval * QTc greater than 450 milliseconds (msec) at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum Tolerated Dose (MTD) of Oral CEP-9722 | Cycle 1 (28 days) | MTD was defined as the highest dose level with 0 or 1 participant experiencing a dose-limiting toxicity (DLT) during cycle 1. DLT was defined as any adverse event (AE) that was considered by the investigator as related or potentially related to CEP-9722 as follows: 1) hematologic: grade 4 hematologic adverse events, grade 3 or greater febrile neutropenia, grade 3 thrombocytopenia lasting 7 days or more, grade 3 thrombocytopenia with bleeding; 2) nonhematologic: grade 3 or 4 nonhematologic AEs; grade 4 vomiting or diarrhea; grade 3 nausea, vomiting, or diarrhea that persisted for 48 hours or more despite optimal medical intervention; QTcF (QTc by Fridericia's cube root formula) greater than 500 milliseconds (msec) (confirmed by a repeat measurement on the same visit). During Cycle 1 of Part 1, any toxicity possibly related to treatment with CEP-9722 that caused a cumulative interruption of dosing for 7 or more days was considered dose limiting. |
| Part 2: Number of Participants With Adverse Events | Up to 8 months | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Poly Adenosine Diphosphate-ribose (PAR) Concentration in Peripheral Blood Monocyte or Mononuclear Cells of CEP-8983 (the Active Moiety of CEP-9722) | Predose (0 hour), 2 and 6 hours postdose on Days 1 and 15 of Cycle 1 | — |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose on Days 1 and 15 of Cycle 1 | — |
| Part 2: Change in QT Interval | Day 1 and Day 15, Cycle 1 | — |
| Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | From the start of the treatment until disease progression/recurrence (up to 168 days) | ORR was assessed by the best tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) during the study using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR: Disappearance of all target and non-target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions. |
| Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose on Days 1 and 15 of Cycle 1 | — |
Countries
United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 parts: Part 1 (to determine the maximum tolerated dose \[MTD\] of single agent oral CEP-9722) and Part 2 (to evaluate the safety and tolerability of the MTD of CEP-9722 identified in Part 1). The study was stopped before reaching its primary objective of determining the MTD of CEP-9722. The lowest dose of CEP-9722 administered was 150 milligrams (mg) and the highest dose was 1000 mg.
Participants by arm
| Arm | Count |
|---|---|
| CEP-9722 Dose 1 QD Participants received Dose 1 of CEP-9722 tablet QD orally with a standard meal for up to 6 cycles of 28 days each. | 3 |
| CEP-9722 Dose 1 BID Participants received Dose 1 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each. | 7 |
| CEP-9722 Dose 2 BID Participants received Dose 2 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each. | 8 |
| CEP-9722 Dose 3 BID Participants received Dose 3 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each. | 6 |
| CEP-9722 Dose 4 BID Participants received Dose 4 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each. | 5 |
| CEP-9722 Dose 5 BID Participants received Dose 5 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each. | 6 |
| CEP-9722 Dose 6 BID Participants received Dose 6 of CEP-9722 tablets BID orally with a standard meal for up to 6 cycles of 28 days each. | 9 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 2 | 0 | 0 | 2 |
| Overall Study | Death | 0 | 0 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Disease progression | 3 | 4 | 3 | 2 | 4 | 4 | 5 |
| Overall Study | Enrolled but not treated | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other than specified | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Stopped taking study medication | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | CEP-9722 Dose 1 QD | Total | CEP-9722 Dose 6 BID | CEP-9722 Dose 5 BID | CEP-9722 Dose 4 BID | CEP-9722 Dose 3 BID | CEP-9722 Dose 2 BID | CEP-9722 Dose 1 BID |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 7 | 57.8 years STANDARD_DEVIATION 11.86 | 57.2 years STANDARD_DEVIATION 13.33 | 59.3 years STANDARD_DEVIATION 16.32 | 50.6 years STANDARD_DEVIATION 12.84 | 60.2 years STANDARD_DEVIATION 7.83 | 57.0 years STANDARD_DEVIATION 13.85 | 63.9 years STANDARD_DEVIATION 6.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 37 Participants | 6 Participants | 5 Participants | 4 Participants | 5 Participants | 7 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 7 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black | 0 Participants | 6 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 3 Participants | 35 Participants | 5 Participants | 5 Participants | 3 Participants | 6 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 34 Participants | 8 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 1 Participants | 10 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 8 / 8 | 6 / 6 | 5 / 5 | 6 / 6 | 9 / 9 |
| serious Total, serious adverse events | 2 / 3 | 1 / 7 | 1 / 8 | 3 / 6 | 2 / 5 | 3 / 6 | 4 / 9 |
Outcome results
Primary
Part 1: Maximum Tolerated Dose (MTD) of Oral CEP-9722
MTD was defined as the highest dose level with 0 or 1 participant experiencing a dose-limiting toxicity (DLT) during cycle 1. DLT was defined as any adverse event (AE) that was considered by the investigator as related or potentially related to CEP-9722 as follows: 1) hematologic: grade 4 hematologic adverse events, grade 3 or greater febrile neutropenia, grade 3 thrombocytopenia lasting 7 days or more, grade 3 thrombocytopenia with bleeding; 2) nonhematologic: grade 3 or 4 nonhematologic AEs; grade 4 vomiting or diarrhea; grade 3 nausea, vomiting, or diarrhea that persisted for 48 hours or more despite optimal medical intervention; QTcF (QTc by Fridericia's cube root formula) greater than 500 milliseconds (msec) (confirmed by a repeat measurement on the same visit). During Cycle 1 of Part 1, any toxicity possibly related to treatment with CEP-9722 that caused a cumulative interruption of dosing for 7 or more days was considered dose limiting.
Time frame: Cycle 1 (28 days)
Population: The MTD determination set included all participants who received at least 1 dose of the study drug during the first cycle. In addition, any participant who experienced a drug related DLT during cycle 1 was considered evaluable regardless of the number of doses received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Population | Part 1: Maximum Tolerated Dose (MTD) of Oral CEP-9722 | NA milligram (mg) |
Primary
Part 2: Number of Participants With Adverse Events
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Up to 8 months
Population: Part 2 of the study was not conducted, hence there were no analyses for any of the Part 2 outcome measures.
Secondary
Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722)
Time frame: Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose on Days 1 and 15 of Cycle 1
Population: The PK analysis set included participants for whom at least 1 PK parameter can be calculated. Here, 'number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Population | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 1309.0 ng*hours/mL | Standard Deviation 1550.61 |
| Overall Population | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 930.3 ng*hours/mL | Standard Deviation 1320.83 |
| CEP-9722 Dose 1 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 2758.5 ng*hours/mL | Standard Deviation 1353.95 |
| CEP-9722 Dose 1 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 3416.3 ng*hours/mL | Standard Deviation 2813.31 |
| CEP-9722 Dose 2 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 10050.0 ng*hours/mL | Standard Deviation 6100.96 |
| CEP-9722 Dose 2 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 3507.7 ng*hours/mL | Standard Deviation 2093.79 |
| CEP-9722 Dose 3 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 13996.2 ng*hours/mL | Standard Deviation 8845.35 |
| CEP-9722 Dose 3 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 4834.0 ng*hours/mL | Standard Deviation 2946.12 |
| CEP-9722 Dose 4 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 16527.4 ng*hours/mL | Standard Deviation 9711.19 |
| CEP-9722 Dose 4 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 10196.6 ng*hours/mL | Standard Deviation 6073.52 |
| CEP-9722 Dose 5 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 40914.7 ng*hours/mL | Standard Deviation 14594.45 |
| CEP-9722 Dose 5 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 12665.3 ng*hours/mL | Standard Deviation 4808.41 |
| CEP-9722 Dose 6 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 49332.9 ng*hours/mL | Standard Deviation 26717.97 |
| CEP-9722 Dose 6 BID | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time of Last Measurable Drug Concentration (AUC0-t) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 19797.2 ng*hours/mL | Standard Deviation 10901.31 |
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722)
Time frame: Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose on Days 1 and 15 of Cycle 1
Population: The pharmacokinetic (PK) analysis set included participants for whom at least 1 PK parameter can be calculated. Here, 'number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Population | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 285.7 nanograms (ng)/milliliter (mL) | Standard Deviation 282.03 |
| Overall Population | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 271.7 nanograms (ng)/milliliter (mL) | Standard Deviation 264.19 |
| CEP-9722 Dose 1 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 695.6 nanograms (ng)/milliliter (mL) | Standard Deviation 425.14 |
| CEP-9722 Dose 1 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 575.5 nanograms (ng)/milliliter (mL) | Standard Deviation 346.35 |
| CEP-9722 Dose 2 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 1585.4 nanograms (ng)/milliliter (mL) | Standard Deviation 921.33 |
| CEP-9722 Dose 2 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 888.7 nanograms (ng)/milliliter (mL) | Standard Deviation 407.73 |
| CEP-9722 Dose 3 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 1808.8 nanograms (ng)/milliliter (mL) | Standard Deviation 921.42 |
| CEP-9722 Dose 3 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 1492.7 nanograms (ng)/milliliter (mL) | Standard Deviation 881.44 |
| CEP-9722 Dose 4 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 3136.8 nanograms (ng)/milliliter (mL) | Standard Deviation 2387.63 |
| CEP-9722 Dose 4 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 2332.4 nanograms (ng)/milliliter (mL) | Standard Deviation 990.45 |
| CEP-9722 Dose 5 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 4306.2 nanograms (ng)/milliliter (mL) | Standard Deviation 1177.27 |
| CEP-9722 Dose 5 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 2753.3 nanograms (ng)/milliliter (mL) | Standard Deviation 537.66 |
| CEP-9722 Dose 6 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 1 | 4121.1 nanograms (ng)/milliliter (mL) | Standard Deviation 1729.05 |
| CEP-9722 Dose 6 BID | Part 1: Maximum Observed Plasma Concentration (Cmax) of CEP-8983 (the Active Moiety of CEP-9722) | Cycle 1 Day 15 | 4679.8 nanograms (ng)/milliliter (mL) | Standard Deviation 2047.07 |
Secondary
Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response
ORR was assessed by the best tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) during the study using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR: Disappearance of all target and non-target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions.
Time frame: From the start of the treatment until disease progression/recurrence (up to 168 days)
Population: The safety analysis set included participants who received at least 1 dose of CEP-9722.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Population | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 67 percentage of participants |
| CEP-9722 Dose 1 BID | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 71 percentage of participants |
| CEP-9722 Dose 2 BID | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 75 percentage of participants |
| CEP-9722 Dose 3 BID | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 83 percentage of participants |
| CEP-9722 Dose 4 BID | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 80 percentage of participants |
| CEP-9722 Dose 5 BID | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 50 percentage of participants |
| CEP-9722 Dose 6 BID | Part 1: Overall Response Rate (ORR) - Percentage of Participants With the Best Tumor Response | 56 percentage of participants |
Secondary
Part 2: Change in QT Interval
Time frame: Day 1 and Day 15, Cycle 1
Population: Due to premature end of the study, Part 2 of the study was not conducted so there was no analysis of QT interval versus PK parameters.
Secondary
Poly Adenosine Diphosphate-ribose (PAR) Concentration in Peripheral Blood Monocyte or Mononuclear Cells of CEP-8983 (the Active Moiety of CEP-9722)
Time frame: Predose (0 hour), 2 and 6 hours postdose on Days 1 and 15 of Cycle 1
Population: Pharmacodynamics was not evaluated in this study because the assay did not work due to sample collection methods.