Neoplasms

Blood and Lymph Conditions

All Conditions

Nutritional and Metabolic Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Protein-Energy Malnutrition

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Decitabine

Onvansertib

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Protein Kinase Inhibitors

Onvansertib, administered in escalating doses orally Day 1 through Day 5 every 28 days (1 cycle) in combination with cytarabine, which will be administered in all cohorts as 20 mg/m\^2 subcutaneously, once daily on Day 1 through Day 10 every 28 days (1 cycle). Onvansertib administration, in combination with cytarabine, will be initiated at a starting dose of 12 mg/m\^2 orally, daily for 5 days. Onvansertib dose will be escalated in successive cohorts until the recommended phase 2 dose is achieved.

Onvansertib will be administered in escalating doses orally, Day 1 through Day 5 every 28 days (1 cycle) in combination with decitabine, administered consistently in all cohorts as 20 mg/m\^2 intravenously over 1 hour on Day 1 through Day 5 every 28 days (1 cycle). Onvansertib administration, in combination with decitabine, will be initiated at a starting dose of 12 mg/m\^2 orally, daily for 5 days (Day 1 through Day 5). Onvansertib dose will be escalated in successive cohorts until the recommended phase 2 dose is achieved.

Onvansertib recommended phase 2 dose, orally Day 1 through Day 5 every 28 days (1 cycle) and decitabine, administered consistently as 20 mg/m\^2 intravenously over 1 hour on Day 1 through Day 5 every 28 days (1 cycle), with treatment modifications or delays based on return of hematopoietic function to baseline or Grade ≤1 toxicity for optimal subject management.

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.

Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)

A Phase 1b/2 Study of PCM-075 (Onvansertib) in Combination With Either Low-Dose Cytarabine or Decitabine in Subjects With Acute Myeloid Leukemia (AML)

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).

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.

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.

Any clinically significant change in electrocardiogram (ECG), physical examination findings, body weight, vital signs, and laboratory parameters were recorded as Adverse Events.

Defined as bone marrow (BM) \<5% blasts in an aspirate with spicules and no blasts with Auer rods or persistence of extramedullary disease.

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.

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.

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.

OS is defined as the time from enrollment until death from any cause and reported as the proportion of participants alive at 12 months.

Cardiff Oncology

Participants included in the Safety Analysis Set were included in this analysis.

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 recommended phase 2 dose (RP2D) of onvansertib.

Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine

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 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 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 recommended phase 2 dose (RP2D) of onvansertib.

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

Participants were administered onvansertib at the recommended phase 2 dose (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.

Phase 2: 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 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.

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

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.

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Nancy Sherman, Head of Clinical Operations

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.

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.

The safety analysis set was comprised of all subjects who received at least one dose of onvansertib.

Number of Participants Who Experienced Dose Limiting Toxicities (DLT)

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 recommended phase 2 dose (RP2D) of Onvansertib.

Phase 1b: Onvansertib + 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 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 recommended phase 2 dose (RP2D) of Onvansertib.

Phase 1b: Onvansertib + Decitabine

Participants were administered Onvansertib at the recommended phase 2 dose (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.

Phase 2: Onvansertib + Decitabine

Per SAP It was pre-planned to report this data by treatment type instead of by dose.

Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status

Only participants in Phase 2 were included in this analysis.

Phase 2: Number of Participants Who Achieved a Complete Response (CR)

Any Adverse Events

Any Serious Adverse Events

Any Treatment-Related Serious Adverse Events

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.

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 5 of each cycle, in order to determine the RP2D of Onvansertib.

Participants were administered onvansertib on Day 1 through Day 5 every 21 to 28 days, in combination with decitabine, administered consistently as 20 mg/m\^2 over 1 hour on Day 1 through Day 5 every 28 days.

Number of Participants With Adverse Events (AEs)

Onvansertib recommended phase 2 dose, orally Day 1 through Day 5 every 28 days (1 cycle) and decitabine, administered consistently as 20 mg/m\^2 intravenously over 1 hour on Day 1 through Day 5 every 28 days (1 cycle), with treatment modifications or delays based on return of hematopoietic function to baseline or Grade ≤1 toxicity for optimal subject management.

Onvansertib: Onvansertib orally

Decitabine: intravenously

Phase 2: Number of Participants Who Achieved a Morphologic Leukemia-free (MLF) State

Only participants included in Phase 2 were used in this analysis.

Phase 2: Number of Participants With Partial Response (PR)

Phase 2: Duration of Response (DOR)

Phase 2: Event-free Survival (EFS)

Only participants included in Phase 2 were included in this analysis.

Phase 2: Overall Survival (OS)

Cycle 1 Day 1

Cycle 1 Day 5

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.

Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib

Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib

Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib

Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib

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 recommended phase 2 dose (RP2D) of onvansertib.

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

Overall Study

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Micronutrients

Hematinics

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Topoisomerase I Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

The first 3 participants will be administered onvansertib orally once a day at a dosing schedule of 12 mg/m\^2 on Day 1 to Day 10 for two cycles, where each cycle is 2 weeks. Depending on the number of dose limiting toxicities (DLTs) experienced in the first 3 participants, additional participants may receive different dosing schedules, determining the dosing schedule to be used in the treatment period. Onvansertib will be administered in combination with 70 mg/m\^2 nanoliposomal irinotecan (nal-IRI), 400 mg/m\^2 leucovorin and 2400 mg/m\^2 fluorouracil (5-FU).

Participants will be administered onvansertib at the dosing schedule selected based on the results of the safety lead-in, in cycles of 2 weeks. Onvansertib will be administered in combination with 70 mg/m\^2 nanoliposomal irinotecan (nal-IRI), 400 mg/m\^2 leucovorin and 2400 mg/m\^2 fluorouracil (5-FU).

Nanoliposomal irinotecan

The main objective of this trial is to assess the efficacy of onvansertib in combination with nanoliposomal irinotecan (nal-IRI), leucovorin, and fluorouracil (5-FU) for treatment of participants with histologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC).

Onvansertib in Combination With Nanoliposomal Irinotecan, Leucovorin, and Fluorouracil for Second-Line Treatment of Participants With Metastatic Pancreatic Ductal Adenocarcinoma

A Phase 2 Study of Onvansertib in Combination With Nanoliposomal Irinotecan, Leucovorin, and Fluorouracil for Second-Line Treatment of Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)	NCT03303339	Acute Myeloid L...	Onvansertib Cytarabine Decitabine	18 Years -	Cardiff Oncology
Onvansertib in Combination With Nanoliposomal Irinotecan, Leucovorin, and Fluorouracil for Second-Line Treatment of Participants With Metastatic Pancreatic Ductal Adenocarcinoma	NCT04752696	Pancreatic Duct...	Onvansertib Nanoliposomal i... Leucovorin Fluorouracil	18 Years -	Cardiff Oncology
Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)	NCT03303339	Acute Myeloid L...	Onvansertib Cytarabine Decitabine	18 Years -	Cardiff Oncology
Onvansertib in Combination With Nanoliposomal Irinotecan, Leucovorin, and Fluorouracil for Second-Line Treatment of Participants With Metastatic Pancreatic Ductal Adenocarcinoma	NCT04752696	Pancreatic Duct...	Onvansertib Nanoliposomal i... Leucovorin Fluorouracil	18 Years -	Cardiff Oncology

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