Childhood Solid Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Primary Central Nervous System Neoplasm, Refractory Malignant Solid Neoplasm, Refractory Primary Central Nervous System Neoplasm
Conditions
Brief summary
This phase I trial studies the side effects and best dose of prexasertib in treating pediatric patients with solid tumors that have come back after a period of time during which the tumor could not be detected or does not respond to treatment. Checkpoint kinase 1 inhibitor LY2606368 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of prexasertib (LY2606368) administered as an intravenous (IV) infusion over 60 minutes, every 14 days of a 28-day cycle to children with recurrent or refractory solid tumors. II. To define and describe the toxicities of LY2606368 administered on this schedule. III. To characterize the pharmacokinetics of LY2606368 in children with recurrent or refractory cancer. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of LY2606368 within the confines of a phase 1 study. II. To examine checkpoint kinase (CHK)1/2 expression status in archival tumor tissue from solid tumor pediatric patients using immunohistochemistry. III. To evaluate tumor tissue for deletion and/or mutation of tumor protein 53 (TP53) as a potential biomarker of Chk1 inhibition. IV. To evaluate autophosphorylation of Chk1 and H2A histone family, member x (H2AX) in peripheral blood mononuclear cells as a potential pharmacodynamic marker of LY2606368 activity. OUTLINE: This is a dose-escalation study. Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacokinetic (PK) study
Correlative studies
DRUGPrexasertib
Given IV
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 21 Years
Healthy volunteers
No
Inclusion criteria
* Patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or in patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG) * Patients must have either measurable or evaluable disease * Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life * Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 % for patients =\< 16 years of age * Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment * \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea) * Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days must have elapsed from last dose of agent; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment * Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1 * Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid * Hematopoietic growth factors: \>= 14 days must have elapsed since the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator * Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days must have elapsed since the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Stem cell infusions (with or without total body irradiation \[TBI\]): * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days must have elapsed after infusion, and no evidence of graft-versus-host disease (GVHD) * Autologous stem cell infusion including boost infusion: \>= 42 days must have elapsed after completion * Cellular therapy: \>= 42 days must have elapsed since the completion of any type of cellular therapy (e.g. modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) * X ray (XRT)/external beam irradiation including protons: \>= 14 days must have elapsed after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation * Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine metaiodobenzylguanidine \[131I-MIBG\]): \>= 42 days must have elapsed since systemically administered radiopharmaceutical therapy * Patients must not have received prior exposure to LY2606368 * For patients with solid tumors without known bone marrow involvement: * Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3 * Platelet count \>= 75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin \>= 8.0 g/dl at baseline (may receive packed red blood cell \[PRBC\] transfusions) * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows: * Age: maximum serum creatinine (mg/dL) * 1 to \< 2 years: 0.6 (male and female) * 2 to \< 6 years: 0.8 (male and female) * 6 to \< 10 years: 1 (male and female) * 10 to \< 13 years: 1.2 (male and female) * 13 to \< 16 years: 1.5 (male), 1.4 (female) * \>= 16 years: 1.7 (male), 1.4 (female) * Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 45 U/L * Serum albumin \>= 2 g/dL * Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by gated radionuclide study * Corrected QT (QTc) =\< 480 msec * Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; If possible, alternative agents should be considered * Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled * Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4) resulting from prior therapy must be =\< grade 2 * For patients with CNS tumors, any baseline neurologic deficit, including seizures, must be stable for at least one week prior to initiating study treatment * All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines * Tissue blocks or slides must be sent if available; if tissue blocks or slides are unavailable, the study chair must be notified prior to study enrollment
Exclusion criteria
* Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method both during and for 3 months after participation in this study; abstinence is an acceptable method of contraception * Corticosteroids: Patients receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid * Investigational drugs: Patients who are currently receiving another investigational drug are not eligible * Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible * Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial * Strong CYP1A2 inhibitors: Patients must not have received strong CYP1A2 inhibitors (ciprofloxacin, fluvoxamine, zafirlukast) for at least 7 days prior to enrollment and must not receive them for the duration of the study * Patients who have an uncontrolled infection are not eligible * Patients who have received a prior solid organ transplantation are not eligible * Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to LY2606368 or to its formulation are not eligible * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Prexasertib | Up to 28 days | Maximum tolerated dose or recommended phase 2 dose of prexasertib assessed by national Cancer Institute (NCI) CTCAE version 4.0 defined as the maximum dose at which fewer that one-third of patients experience a dose limiting toxicity in cycle 1 |
| Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib | Up to 28 days | Number of patients with DLT to Prexasertib by dose level and study part. |
| Area Under the Concentration Time Curve for Prexasertib | Up to 8 hours | Median (min, max) area under the concentration by time curve for prexasertib assessed at 1, 1.5, 2, 4, and 8 hours on day 1 post infusion by dose level and study part |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor Activity of Prexasertib | Up to 2 years | Number of response evaluable patients with response (CR/PR) using the RECIST guideline version 1.1 including CR: disappearance of all target and non-target lesions; PR: at least 30% decrease in the sum of the diameters of target lesions by dose level and study part |
| Autophosphorylation of CHK1 and H2AX | Up to 2 years | Median (min, max) autophosphorylation of CHK1 and H2AX in peripheral blood mononuclear cells by dose level and study part. |
| CHK1/2 Expression Status | Up to 2 years | Number of patients with CHK1/2 expression by percent of tumor cells with CHK1/2 expression defined by quartiles. |
| TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | Up to 2 years | Number of patients with TP53 deletion and/or mutation of Trp53 by percent of tumor cells with TP53 deletion and/or mutation of Trp53 defined by quartiles. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A Dose Level 1: 80 mg/m^2 Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. | 6 |
| Part A Dose Level 2: 100 mg/m^2 Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. | 6 |
| Part A Dose Level 3: 125 mg/m^2 Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. | 6 |
| Part A Dose Level 4: 150 mg/m^2 Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. | 6 |
| Part PK Dose Level 4: 150 mg/m^2 Patients receive prexasertib IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. | 6 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 5 | 6 | 5 | 4 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Part A Dose Level 1: 80 mg/m^2 | Part A Dose Level 2: 100 mg/m^2 | Part A Dose Level 3: 125 mg/m^2 | Part A Dose Level 4: 150 mg/m^2 | Part PK Dose Level 4: 150 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 5 Participants | 4 Participants | 4 Participants | 6 Participants | 25 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 5 Participants |
| Age, Continuous | 8.5 years | 14 years | 10 years | 16.5 years | 4.5 years | 9.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 5 Participants | 6 Participants | 4 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 2 Participants | 6 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 5 Participants | 6 Participants | 0 Participants | 21 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 1 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 3 / 6 | 3 / 6 | 3 / 6 | 2 / 6 | 4 / 6 |
Outcome results
Primary
Area Under the Concentration Time Curve for Prexasertib
Median (min, max) area under the concentration by time curve for prexasertib assessed at 1, 1.5, 2, 4, and 8 hours on day 1 post infusion by dose level and study part
Time frame: Up to 8 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Prexasertib) | Area Under the Concentration Time Curve for Prexasertib | 1718.7 hr*ng/mL |
| Part A Dose Level 2: 100 mg/m^2 | Area Under the Concentration Time Curve for Prexasertib | 2285.5 hr*ng/mL |
| Part A Dose Level 3: 125 mg/m^2 | Area Under the Concentration Time Curve for Prexasertib | 2534.4 hr*ng/mL |
| Part A Dose Level 4: 150 mg/m^2 | Area Under the Concentration Time Curve for Prexasertib | 4206.6 hr*ng/mL |
| Part PK Dose Level 4: 150 mg/m^2 | Area Under the Concentration Time Curve for Prexasertib | 3097.7 hr*ng/mL |
Primary
Maximum Tolerated Dose (MTD) of Prexasertib
Maximum tolerated dose or recommended phase 2 dose of prexasertib assessed by national Cancer Institute (NCI) CTCAE version 4.0 defined as the maximum dose at which fewer that one-third of patients experience a dose limiting toxicity in cycle 1
Time frame: Up to 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Prexasertib) | Maximum Tolerated Dose (MTD) of Prexasertib | 150 mg/m^2 |
Primary
Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib
Number of patients with DLT to Prexasertib by dose level and study part.
Time frame: Up to 28 days
Population: All Toxicity evaluable patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Prexasertib) | Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | Number of Patients With Dose Limiting Toxicity (DLT) to Prexasertib | 0 Participants |
Secondary
Antitumor Activity of Prexasertib
Number of response evaluable patients with response (CR/PR) using the RECIST guideline version 1.1 including CR: disappearance of all target and non-target lesions; PR: at least 30% decrease in the sum of the diameters of target lesions by dose level and study part
Time frame: Up to 2 years
Population: Eligible Patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Prexasertib) | Antitumor Activity of Prexasertib | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | Antitumor Activity of Prexasertib | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | Antitumor Activity of Prexasertib | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | Antitumor Activity of Prexasertib | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | Antitumor Activity of Prexasertib | 0 Participants |
Secondary
Autophosphorylation of CHK1 and H2AX
Median (min, max) autophosphorylation of CHK1 and H2AX in peripheral blood mononuclear cells by dose level and study part.
Time frame: Up to 2 years
Population: Testing failed. Data not available to be reported for outcome measure.
Secondary
CHK1/2 Expression Status
Number of patients with CHK1/2 expression by percent of tumor cells with CHK1/2 expression defined by quartiles.
Time frame: Up to 2 years
Population: All eligible patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Prexasertib) | CHK1/2 Expression Status | 51-75% cells positive | 2 Participants |
| Treatment (Prexasertib) | CHK1/2 Expression Status | 0% Negative | 2 Participants |
| Treatment (Prexasertib) | CHK1/2 Expression Status | 76-100% cells positive | 1 Participants |
| Treatment (Prexasertib) | CHK1/2 Expression Status | 1-25% cells positive | 0 Participants |
| Treatment (Prexasertib) | CHK1/2 Expression Status | 26-50% cells positive | 1 Participants |
| Part A Dose Level 2: 100 mg/m^2 | CHK1/2 Expression Status | 51-75% cells positive | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | CHK1/2 Expression Status | 26-50% cells positive | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | CHK1/2 Expression Status | 1-25% cells positive | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | CHK1/2 Expression Status | 76-100% cells positive | 1 Participants |
| Part A Dose Level 2: 100 mg/m^2 | CHK1/2 Expression Status | 0% Negative | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | CHK1/2 Expression Status | 26-50% cells positive | 1 Participants |
| Part A Dose Level 3: 125 mg/m^2 | CHK1/2 Expression Status | 0% Negative | 1 Participants |
| Part A Dose Level 3: 125 mg/m^2 | CHK1/2 Expression Status | 1-25% cells positive | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | CHK1/2 Expression Status | 51-75% cells positive | 1 Participants |
| Part A Dose Level 3: 125 mg/m^2 | CHK1/2 Expression Status | 76-100% cells positive | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 76-100% cells positive | 3 Participants |
| Part A Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 0% Negative | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 51-75% cells positive | 1 Participants |
| Part A Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 26-50% cells positive | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 1-25% cells positive | 1 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 26-50% cells positive | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 51-75% cells positive | 2 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 0% Negative | 1 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 76-100% cells positive | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | CHK1/2 Expression Status | 1-25% cells positive | 1 Participants |
Secondary
TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition
Number of patients with TP53 deletion and/or mutation of Trp53 by percent of tumor cells with TP53 deletion and/or mutation of Trp53 defined by quartiles.
Time frame: Up to 2 years
Population: Response evaluable Patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Prexasertib) | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 26-50% cells positive | 1 Participants |
| Treatment (Prexasertib) | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 1-25% cells positive | 0 Participants |
| Treatment (Prexasertib) | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 0% Negative | 1 Participants |
| Treatment (Prexasertib) | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 76-100% cells positive | 2 Participants |
| Treatment (Prexasertib) | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 51-75% cells positive | 2 Participants |
| Part A Dose Level 2: 100 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 76-100% cells positive | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 0% Negative | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 1-25% cells positive | 0 Participants |
| Part A Dose Level 2: 100 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 26-50% cells positive | 1 Participants |
| Part A Dose Level 2: 100 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 51-75% cells positive | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 1-25% cells positive | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 26-50% cells positive | 0 Participants |
| Part A Dose Level 3: 125 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 0% Negative | 1 Participants |
| Part A Dose Level 3: 125 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 51-75% cells positive | 1 Participants |
| Part A Dose Level 3: 125 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 76-100% cells positive | 1 Participants |
| Part A Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 26-50% cells positive | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 1-25% cells positive | 2 Participants |
| Part A Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 51-75% cells positive | 1 Participants |
| Part A Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 0% Negative | 0 Participants |
| Part A Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 76-100% cells positive | 2 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 51-75% cells positive | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 26-50% cells positive | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 0% Negative | 0 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 76-100% cells positive | 3 Participants |
| Part PK Dose Level 4: 150 mg/m^2 | TP53 Deletion and/or Mutation in Tumor Tissue as a Potential Biomarker of Chk1 Inhibition | 1-25% cells positive | 1 Participants |