Acute Myeloid Leukemia
Conditions
Keywords
PLK1, PLK Inhibitor, Onvansertib
Brief summary
The purpose of the phase 1b/2 study is to determine whether Onvansertib given orally daily for 5 consecutive days every 28 days is safe and tolerable in adult patients who have relapsed/refractory Acute Myeloid Leukemia (AML), or are ineligible for intensive induction therapy, and to determine the maximum tolerated dose and recommended phase 2 dose of Onvansertib in combination with decitabine or Onvansertib in combination with low-dose cytarabine. In the phase 2 portion of the study, Onvansertib in combination with decitabine will be studied to provide further data on the safety profile of the combination and to preliminarily assess the activity of the chosen combination in patients with untreated AML who are not candidates for aggressive induction therapy, or who have received one prior treatment for their AML.
Interventions
Sponsors
Cardiff Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Disease Status and Prior Therapy: 1. Histologically confirmed AML with \>20% blasts 2. Phase 1b: Participants with AML who are refractory to or have relapsed after initial treatment for their disease, with no more than three prior lines of therapy. Participants who have received prior treatment with cytarabine or decitabine are not excluded. 3. Phase 2: i. Participants with AML who are refractory to, or have relapsed after, initial treatment for their disease, with no more than one prior line of therapy, and are judged not to be candidates for re-induction therapy that includes hematopoietic cell transplantation. Participants who have received prior cytarabine or decitabine are not excluded. OR ii. Participants with newly diagnosed, untreated AML ineligible for, or who have refused, standard intensive induction therapy 2. Age ≥18 years 3. ECOG performance status ≤2 4. Participants must be willing and able to review, understand, and provide written consent before starting any study-specific procedures or therapy. 5. All men and women must agree to practice effective contraception during the entire study period and after discontinuing study drug, unless documentation of infertility exists 1. Sexually active, fertile women must use two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least 6 months after discontinuing study drug 2. Sexually active men and their sexual partners must use effective contraceptive methods from the time of participant informed consent and until at least 3 months after discontinuing study drug
Exclusion criteria
1. Treatment-related AML or acute promyelocytic leukemia (APL) 2. Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death 3. Clinical evidence of active central nervous system leukemia at the time of screening 4. Alanine aminotransferase and/or aspartate aminotransferase ≥2.5 x upper limit of normal (ULN) 5. Total bilirubin \> 2.0 mg/dL (or \> 3.0 mg/dL in participants with documented Gilbert syndrome) 6. Serum creatinine ≥2.0 mg/dL 7. New York Heart Association Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition, or hypertensive or metabolic condition 8. Myocardial infarction in the previous 12 weeks (from the start of treatment) 9. Resting left ventricular ejection fraction \<50% at the time of screening 10. QT (Interval from the beginning of the QRS complex to the end of the T wave on an electrocardiogram) interval with Fridericia's correction \[QTcF\] \>450 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of potentially correctible causes of QT prolongation (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during screening and that result may be used to determine eligibility. 11. Active and uncontrolled disease (other than AML) or infection as judged by the treating physician 12. Treatment with systemic therapy for the primary disease within 14 days (except for hydroxyurea or isolated doses of cytarabine or decitabine for white blood cell control) 13. Grade 2 or greater toxicities from prior therapy, except for Grade 2 toxicities that are not expected to resolve and that in the judgment of the Investigator do not pose a significant safety risk to subject participation. 14. Participants with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the participant's ability to sign the informed consent form or his/her ability to cooperate and participate in the study, or to interfere with the interpretation of the results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | Up to Day 28 of Cycle 1 | Dose-limiting toxicities were defined as events related to onvansertib that were considered an adverse reaction or suspected adverse reaction during the first cycle of therapy and that fulfilled one of the following: Hematologic (persistent pancytopenia resistant to current standards of care that continues for ≥42 days and is not related to leukemic infiltration or another cause unrelated to study therapy) or Non-Hematologic (any Grade 3 abnormalities that persist \>7 days without decreasing in severity despite standards of care, are clinically significant, or that are Grade 4 and symptomatic). |
| Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status | Baseline and end of study (approximately up to up to 27 months) | ECOG performance status was determined using 6-point scale from 0-5, with 0 meaning a participant was fully active/able to carry on all pre-disease activities without restriction and 5 meaning the participant was deceased. |
| Phase 2: Number of Participants Who Achieved a Complete Response (CR) | Up to 27 months | Complete Response also includes Complete Response with Incomplete Blood Count Recovery (CRi). Complete response is defined by the following criteria: Morphologic leukemia-free state plus: * Subject is independent of transfusions * Absolute neutrophil count of \>1000/mm3 * Platelets of ≥100,000/mm3 Complete response with incomplete blood count recovery meets all criteria for CR except for either neutropenia (ANC \<1000/mm3) or thrombocytopenia (\<100,000/mm3) but must include transfusion independence. |
| Number of Participants With Adverse Events (AEs) | Baseline up to 30 days after last dose of study drug (up to 27 months) | Any clinically significant change in electrocardiogram (ECG), physical examination findings, body weight, vital signs, and laboratory parameters were recorded as Adverse Events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Overall Survival (OS) | 12 Months | OS is defined as the time from enrollment until death from any cause and reported as the proportion of participants alive at 12 months. |
| Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1: Days 1 and 5 | — |
| Phase 2: Number of Participants Who Achieved a Morphologic Leukemia-free (MLF) State | Up to 27 months | Defined as bone marrow (BM) \<5% blasts in an aspirate with spicules and no blasts with Auer rods or persistence of extramedullary disease. |
| Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1: Days 1 and 5 | — |
| Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1: Days 1 and 5 | — |
| Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1: Days 1 and 5 | — |
| Phase 2: Number of Participants With Partial Response (PR) | Up to 27 months | PR criteria includes all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate and a normalization of blood counts. |
| Phase 2: Duration of Response (DOR) | Up to 27 months | Duration of Response (DOR) is the time (in months) from the first response of CR, CRi or PR until recurrence of or progression of disease (or death). MLF State is also included as a response when calculating DOR. Responding subjects without death or progression will be censored at the date of their last evaluable disease assessment. |
| Phase 2: Event-free Survival (EFS) | 12 Months | EFS is defined as the time from enrollment until disease progression or death from any cause and reported as the proportion of participants event free at 12 months. |
Countries
United States
Participant flow
Recruitment details
72 participants were enrolled across 8 sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with cytarabine at a dose of 20mg/m\^2 once daily on Day 1 up to Day 10 of each cycle, in order to determine the RP2D of onvansertib. | 3 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with cytarabine at a dose of 20mg/m\^2 once daily on Day 1 up to Day 10 of each cycle, in order to determine the RP2D of onvansertib. | 3 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with cytarabine at a dose of 20mg/m\^2 once daily on Day 1 up to Day 10 of each cycle, in order to determine the RP2D of onvansertib. | 3 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with cytarabine at a dose of 20mg/m\^2 once daily on Day 1 up to Day 10 of each cycle, in order to determine the RP2D of onvansertib. | 3 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with cytarabine at a dose of 20mg/m\^2 once daily on Day 1 up to Day 10 of each cycle, in order to determine the RP2D of onvansertib. | 5 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle, in order to determine the RP2D of onvansertib | 4 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle, in order to determine the RP2D of onvansertib | 3 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle, in order to determine the RP2D of onvansertib | 3 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle, in order to determine the RP2D of onvansertib | 4 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle, in order to determine the RP2D of onvansertib | 3 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine Participants were administered escalating doses of onvansertib starting at 12mg/m\^2 on Day 1 up to Day 5 of each cycle (where each cycle is 28 days) in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle, in order to determine the RP2D of onvansertib | 6 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine Participants were administered onvansertib at the RP2D on Day 1 up to Day 5 of each cycle (where each cycle is 28 days), in combination with decitabine at a dose of 20mg/m\^2 once daily on Day 1 up to day 10 of each cycle. | 32 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 2 | 1 | 4 | 2 | 2 | 2 | 3 | 3 | 4 | 24 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Safety/Non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Phase 2: Onvansertib 60 mg/m^2 + Decitabine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 6 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 62 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 5 Participants | 29 Participants |
| Sex: Female, Male Female | 25 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 47 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 19 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 | 2 / 3 | 1 / 3 | 4 / 5 | 2 / 4 | 2 / 3 | 2 / 3 | 3 / 4 | 3 / 3 | 4 / 6 | 24 / 32 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 5 / 5 | 4 / 4 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 6 / 6 | 32 / 32 |
| serious Total, serious adverse events | 2 / 3 | 3 / 3 | 1 / 3 | 2 / 3 | 3 / 5 | 2 / 4 | 3 / 3 | 3 / 3 | 4 / 4 | 2 / 3 | 5 / 6 | 27 / 32 |
Outcome results
Primary
Number of Participants Who Experienced Dose Limiting Toxicities (DLT)
Dose-limiting toxicities were defined as events related to onvansertib that were considered an adverse reaction or suspected adverse reaction during the first cycle of therapy and that fulfilled one of the following: Hematologic (persistent pancytopenia resistant to current standards of care that continues for ≥42 days and is not related to leukemic infiltration or another cause unrelated to study therapy) or Non-Hematologic (any Grade 3 abnormalities that persist \>7 days without decreasing in severity despite standards of care, are clinically significant, or that are Grade 4 and symptomatic).
Time frame: Up to Day 28 of Cycle 1
Population: The safety analysis set was comprised of all subjects who received at least one dose of onvansertib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Number of Participants Who Experienced Dose Limiting Toxicities (DLT) | 2 Participants |
Primary
Number of Participants With Adverse Events (AEs)
Any clinically significant change in electrocardiogram (ECG), physical examination findings, body weight, vital signs, and laboratory parameters were recorded as Adverse Events.
Time frame: Baseline up to 30 days after last dose of study drug (up to 27 months)
Population: The safety analysis set was comprised of all subjects who received at least one dose of onvansertib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 0 Participants |
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 2 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 1 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 0 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 1 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 1 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 2 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 5 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 0 Participants |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 0 Participants |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 4 Participants |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 2 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 0 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 1 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 4 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 4 Participants |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 0 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 1 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 2 Participants |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 6 Participants |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 3 Participants |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 5 Participants |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Treatment-Related Serious Adverse Events | 5 Participants |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Adverse Events | 32 Participants |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Number of Participants With Adverse Events (AEs) | Any Serious Adverse Events | 27 Participants |
Primary
Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
ECOG performance status was determined using 6-point scale from 0-5, with 0 meaning a participant was fully active/able to carry on all pre-disease activities without restriction and 5 meaning the participant was deceased.
Time frame: Baseline and end of study (approximately up to up to 27 months)
Population: Per SAP It was pre-planned to report this data by treatment type instead of by dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status | 11 Participants |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status | 14 Participants |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status | 22 Participants |
Primary
Phase 2: Number of Participants Who Achieved a Complete Response (CR)
Complete Response also includes Complete Response with Incomplete Blood Count Recovery (CRi). Complete response is defined by the following criteria: Morphologic leukemia-free state plus: * Subject is independent of transfusions * Absolute neutrophil count of \>1000/mm3 * Platelets of ≥100,000/mm3 Complete response with incomplete blood count recovery meets all criteria for CR except for either neutropenia (ANC \<1000/mm3) or thrombocytopenia (\<100,000/mm3) but must include transfusion independence.
Time frame: Up to 27 months
Population: Only participants in Phase 2 were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 2: Number of Participants Who Achieved a Complete Response (CR) | 3 Participants |
Secondary
Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib
Time frame: Cycle 1: Days 1 and 5
Population: The PK analysis set consisted of all subjects in the safety analysis set who received onvansertib and had adequate plasma onvansertib concentration data as determined by the PK scientist.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 1197.93 h*ng/mL | Geometric Coefficient of Variation 23.42 |
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 1868.69 h*ng/mL | Geometric Coefficient of Variation 70.99 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 772.68 h*ng/mL | Geometric Coefficient of Variation 26.21 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 3626.44 h*ng/mL | Geometric Coefficient of Variation 5.33 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 2534.22 h*ng/mL | Geometric Coefficient of Variation 31.05 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 5343.01 h*ng/mL | Geometric Coefficient of Variation 2.11 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 2761.11 h*ng/mL | Geometric Coefficient of Variation 36.97 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 7415.04 h*ng/mL | Geometric Coefficient of Variation 64.35 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 19470.17 h*ng/mL | Geometric Coefficient of Variation 17.1 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 5386.69 h*ng/mL | Geometric Coefficient of Variation 59.16 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 1099.43 h*ng/mL | Geometric Coefficient of Variation 29.81 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 1868.69 h*ng/mL | Geometric Coefficient of Variation 70.99 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 3626.44 h*ng/mL | Geometric Coefficient of Variation 5.33 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 2789.81 h*ng/mL | Geometric Coefficient of Variation 25.3 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 3257.57 h*ng/mL | Geometric Coefficient of Variation 53.53 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 5343.01 h*ng/mL | Geometric Coefficient of Variation 2.11 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 4084.18 h*ng/mL | Geometric Coefficient of Variation 27.94 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 7415.04 h*ng/mL | Geometric Coefficient of Variation 64.35 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 9599.19 h*ng/mL | Geometric Coefficient of Variation 25.01 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 19470.17 h*ng/mL | Geometric Coefficient of Variation 17.1 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 12981.17 h*ng/mL | Geometric Coefficient of Variation 56.18 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 9087.77 h*ng/mL | Geometric Coefficient of Variation 57.43 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 5 | 11767.29 h*ng/mL | Geometric Coefficient of Variation 39.78 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib | Cycle 1 Day 1 | 6280.28 h*ng/mL | Geometric Coefficient of Variation 46.85 |
Secondary
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib
Time frame: Cycle 1: Days 1 and 5
Population: The PK analysis set consisted of all subjects in the safety analysis set who received onvansertib and had adequate plasma onvansertib concentration data as determined by the PK scientist.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 92.57 ng/mL | Geometric Coefficient of Variation 5.66 |
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 139.22 ng/mL | Geometric Coefficient of Variation 55.12 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 69.56 ng/mL | Geometric Coefficient of Variation 28.73 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 103.27 ng/mL | Geometric Coefficient of Variation 43.01 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 251.16 ng/mL | Geometric Coefficient of Variation 85.37 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 298.63 ng/mL | Geometric Coefficient of Variation 66.58 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 256.11 ng/mL | Geometric Coefficient of Variation 24.96 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 339.52 ng/mL | Geometric Coefficient of Variation 31.25 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 857.29 ng/mL | Geometric Coefficient of Variation 38.54 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 626.18 ng/mL | Geometric Coefficient of Variation 61.37 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 80.15 ng/mL | Geometric Coefficient of Variation 21.33 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 146.10 ng/mL | Geometric Coefficient of Variation 56.75 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 197.67 ng/mL | Geometric Coefficient of Variation 85.14 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 129.18 ng/mL | Geometric Coefficient of Variation 93.78 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 309.86 ng/mL | Geometric Coefficient of Variation 72.47 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 398.38 ng/mL | Geometric Coefficient of Variation 32.95 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 410.42 ng/mL | Geometric Coefficient of Variation 26.38 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 496.24 ng/mL | Geometric Coefficient of Variation 52.72 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 724.76 ng/mL | Geometric Coefficient of Variation 57.33 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 955.59 ng/mL | Geometric Coefficient of Variation 54.78 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 1137.16 ng/mL | Geometric Coefficient of Variation 61.56 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 737.21 ng/mL | Geometric Coefficient of Variation 43.06 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 5 | 861.86 ng/mL | Geometric Coefficient of Variation 46.68 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib | Cycle 1 Day 1 | 515.63 ng/mL | Geometric Coefficient of Variation 43.47 |
Secondary
Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib
Time frame: Cycle 1: Days 1 and 5
Population: The PK analysis set consisted of all subjects in the safety analysis set who received onvansertib and had adequate plasma onvansertib concentration data as determined by the PK scientist.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 16.413 Hours | Geometric Coefficient of Variation 28.186 |
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 11.294 Hours | Geometric Coefficient of Variation 11.098 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 7.993 Hours | — |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 12.561 Hours | Geometric Coefficient of Variation 38.983 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 12.197 Hours | Geometric Coefficient of Variation 71.258 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 12.246 Hours | Geometric Coefficient of Variation 38.286 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 7.321 Hours | Geometric Coefficient of Variation 8.094 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 11.747 Hours | Geometric Coefficient of Variation 63.901 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 7.309 Hours | Geometric Coefficient of Variation 99.539 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 14.484 Hours | Geometric Coefficient of Variation 32.002 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 16.960 Hours | Geometric Coefficient of Variation 54.43 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 13.282 Hours | Geometric Coefficient of Variation 39.361 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 13.795 Hours | Geometric Coefficient of Variation 28.866 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 9.082 Hours | Geometric Coefficient of Variation 25.356 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 9.394 Hours | Geometric Coefficient of Variation 20.598 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 10.713 Hours | Geometric Coefficient of Variation 23.782 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 16.337 Hours | Geometric Coefficient of Variation 27.365 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 11.389 Hours | Geometric Coefficient of Variation 39.53 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 12.917 Hours | Geometric Coefficient of Variation 41.715 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 44.018 Hours | — |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 12.633 Hours | Geometric Coefficient of Variation 50.655 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 12.378 Hours | Geometric Coefficient of Variation 10.948 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 5 | 14.060 Hours | Geometric Coefficient of Variation 28.874 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib | Cycle 1 Day 1 | 11.904 Hours | Geometric Coefficient of Variation 29.602 |
Secondary
Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib
Time frame: Cycle 1: Days 1 and 5
Population: The PK analysis set consisted of all subjects in the safety analysis set who received onvansertib and had adequate plasma onvansertib concentration data as determined by the PK scientist.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 1.961 Hours | Geometric Coefficient of Variation 81.664 |
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 1.844 Hours | Geometric Coefficient of Variation 62.646 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.548 Hours | Geometric Coefficient of Variation 96.282 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 2.892 Hours | Geometric Coefficient of Variation 37.244 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.301 Hours | Geometric Coefficient of Variation 84.217 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 2.267 Hours | Geometric Coefficient of Variation 82.486 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 1.384 Hours | Geometric Coefficient of Variation 103.829 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 1.474 Hours | Geometric Coefficient of Variation 67.999 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 2.148 Hours | Geometric Coefficient of Variation 55.159 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.071 Hours | Geometric Coefficient of Variation 39.57 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 3.102 Hours | Geometric Coefficient of Variation 31.792 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 2.438 Hours | Geometric Coefficient of Variation 24.524 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 1.583 Hours | Geometric Coefficient of Variation 96.305 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.365 Hours | Geometric Coefficient of Variation 78.396 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 1.288 Hours | Geometric Coefficient of Variation 41.249 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 3.145 Hours | Geometric Coefficient of Variation 33.877 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 1.373 Hours | Geometric Coefficient of Variation 49.676 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 3.161 Hours | Geometric Coefficient of Variation 41.35 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.893 Hours | Geometric Coefficient of Variation 135.893 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 3.161 Hours | Geometric Coefficient of Variation 41.35 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 3.189 Hours | Geometric Coefficient of Variation 29.775 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.435 Hours | Geometric Coefficient of Variation 53.682 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 5 | 2.665 Hours | Geometric Coefficient of Variation 51.333 |
| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib | Cycle 1 Day 1 | 2.725 Hours | Geometric Coefficient of Variation 69.661 |
Secondary
Phase 2: Duration of Response (DOR)
Duration of Response (DOR) is the time (in months) from the first response of CR, CRi or PR until recurrence of or progression of disease (or death). MLF State is also included as a response when calculating DOR. Responding subjects without death or progression will be censored at the date of their last evaluable disease assessment.
Time frame: Up to 27 months
Population: Only participants in Phase 2 were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 2: Duration of Response (DOR) | 5.2 months |
Secondary
Phase 2: Event-free Survival (EFS)
EFS is defined as the time from enrollment until disease progression or death from any cause and reported as the proportion of participants event free at 12 months.
Time frame: 12 Months
Population: Only participants in Phase 2 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 2: Event-free Survival (EFS) | 0.1 Proportion of Participants |
Secondary
Phase 2: Number of Participants Who Achieved a Morphologic Leukemia-free (MLF) State
Defined as bone marrow (BM) \<5% blasts in an aspirate with spicules and no blasts with Auer rods or persistence of extramedullary disease.
Time frame: Up to 27 months
Population: Only participants in Phase 2 were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 2: Number of Participants Who Achieved a Morphologic Leukemia-free (MLF) State | 1 Participants |
Secondary
Phase 2: Number of Participants With Partial Response (PR)
PR criteria includes all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate and a normalization of blood counts.
Time frame: Up to 27 months
Population: Only participants included in Phase 2 were used in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 2: Number of Participants With Partial Response (PR) | 0 Participants |
Secondary
Phase 2: Overall Survival (OS)
OS is defined as the time from enrollment until death from any cause and reported as the proportion of participants alive at 12 months.
Time frame: 12 Months
Population: Only participants included in Phase 2 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | Phase 2: Overall Survival (OS) | 0.2 Proportion of Participants |