A Phase 1/2 interventional study of Onvansertib and Bevacizumab in Metastatic Colorectal Cancer and KRAS Gene Mutation, sponsored by Cardiff Oncology. Completed at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-04.
Sponsored by Cardiff Oncology · Phase 1/2, Interventional, and Treatment
The purpose of the Phase 1b/2 study is to determine the safety and efficacy of Onvansertib, administered orally, daily on Day 1-5 and Day 15-19 of each 28-day cycle, in combination with FOLFIRI + Bevacizumab, as second-line treatment in adult participants who have metastatic colorectal cancer with a KRAS mutation. Participants must have histologically confirmed metastatic and unresectable disease, and previously failed treatment or be intolerant to fluoropyrimidine and oxaliplatin with or without bevacizumab.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's enrollment of 68 is below the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Cardiff Oncology is the lead sponsor of 7 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Has failed treatment or is intolerant of fluoropyrimidine and oxaliplatin with or without bevacizumab.
Exclusion Criteria:
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, non-healing or healing wounds, symptomatic congestive heart failure (CHF) Class II or higher according to the (NYHA) Functional Classification, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
The following are exclusion criteria for bevacizumab:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Phase 1b: Onvansertib escalating starting dose of 12 mg/m\^2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab. This Phase 1b portion of the study has been completed. Phase 2: Onvansertib Recommended Phase 2 Dose (RP2D) of 15 mg/m\^2 orally Day 1 through Day 5 and Day 15 through Day 19 of every 28-day cycle in combination with FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab, with treatment modifications or delays based on unresolved toxicity experienced during a previous cycle.
Drug: Onvansertib · Biological: Bevacizumab · Drug: FOLFIRI
Onvansertib orally.
Also known as: PCM-075
Bevacizumab intravenously.
Also known as: Avastin®
FOLFIRI intravenously.
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were defined as a Grade 4 hematologic adverse events (AEs), Grade ≥ 3 non-hematologic AEs that were considered related to the study drug and that did not resolve within 14 days following presentation with standard management and care, Grade ≥ 3 thrombocytopenia with bleeding, neutropenic fever, any death not clearly due to the underlying disease or extraneous causes, or any change in liver function that met Hy's Law criteria of a DLT.
Time frame: Up to Day 28
Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
AEs were defined as any untoward medical occurrence associated with the use of a drug in humans. TEAEs are defined as any AE that started on or after the first day of study treatment and within 30 days of the last administration of study treatment, or that worsened on or after the first day of study treatment. AE severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 on a scale from Grade 1 (mild) to Grade 5 (death). An AE was considered "serious" if it resulted in death, life-threatening AE, hospitalization or prolongation of hospitalization, persistent or significant incapacity, or congenital anomaly/birth defect. The Investigator determined relatedness to the use of onvansertib. Clinically significant changes in vital signs, laboratory parameters, electrocardiograms, physical examinations, weight, and Eastern Cooperative Oncology Group (ECOG) performance status were reported as AEs.
Time frame: Up to a maximum of 81 weeks
All-Treated Analysis Set: Objective Response Rate (ORR)
ORR was defined as the percentage of participants documented to have a confirmed complete response (CR) or partial response (PR) using the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1). Two-sided 95% confidence interval (CI) was calculated using the exact binomial Clopper-Pearson method. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Time frame: Up to a maximum of 131 weeks
Phase 2: Number of Participants With TEAEs
AEs were defined as any untoward medical occurrence associated with the use of a drug in humans. TEAEs are defined as any AE that started on or after the first day of study treatment and within 30 days of the last administration of study treatment, or that worsened on or after the first day of study treatment. AE severity was graded according to the CTCAE version 5.0 on a scale from Grade 1 (mild) to Grade 5 (death). An AE was considered "serious" if it resulted in death, life-threatening AE, hospitalization or prolongation of hospitalization, persistent or significant incapacity, or congenital anomaly/birth defect. The Investigator determined relatedness to the use of onvansertib. Clinically significant changes in vital signs, laboratory parameters, electrocardiograms, physical examinations, weight, and ECOG performance status were reported as AEs.
Time frame: Up to a maximum of 131 weeks
All-Treated Analysis Set: Disease Control Rate (DCR)
DCR was defined as the percentage of participants documented to have a confirmed CR, PR or stable disease (SD) using the RECIST v1.1. Two-sided 95% CI was calculated using the exact binomial Clopper-Pearson method. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Time frame: Up to a maximum of 131 weeks
All-Treated Analysis Set: Progression-free Survival (PFS)
PFS was defined as the time in months from the date of first administration of study treatment until the first observation of PD or death due to any cause, whichever occurs first, i.e.: (date of first PD or death date of first administration of study treatment +1)/30.4375. Median and 95% CI were calculated using the Kaplan-Meier method. Participants who did not have an observed documented PD or death from any cause were censored at the latest tumor response assessment date. PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Time frame: Up to a maximum of 131 weeks
All-Treated Analysis Set: Duration of Response (DoR)
DoR was calculated as the (date of first documented tumor progression or death due to any cause minus date of first documentation of a subsequently confirmed objective response plus 1)/30.4375. Participants who did not have an observed documented PD or death from any cause were censored at the latest tumor response assessment date.
Time frame: Up to a maximum of 131 weeks
All-Treated Analysis Set: Overall Survival (OS)
OS was defined as the time in months from the date of first administration of study treatment until death due to any cause, i.e.: (Date of death date of first administration of study treatment +1)/30.4375. Participants who did not have documented death from any cause were censored at the date they were last known to be alive. OS was added as an endpoint with Protocol Amendment #1, therefore, OS data was only collected from then onward.
Time frame: Up to a maximum of 131 weeks
All-Treated Analysis Set: Percentage Change in KRAS-mutant Allelic Fraction (MAF)
Blood samples were analyzed for the presence of circulating tumor DNA (ctDNA \[including KRAS mutations\]). KRAS-mutant allelic burden was based on liquid biopsies.
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 (28-day cycle length)
Phase 2: Observed Plasma Concentration at the End of Each Dosing Interval (Ctrough) of Onvansertib
Plasma pharmacokinetic (PK) parameters for onvansertib were estimated using non-compartmental methods.
Time frame: Pre-dose on Day 1 of Cycles 1 and 3 (28-day cycle length)
The study enrolled a total of 68 participants from 7 investigative sites in the United States between June 2019 and January 2024.
| Milestone | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| Started | 6 | 8 | 6 | 48 |
| Completed | 0 | 0 | 0 | 1 |
| Not completed | 6 | 8 | 6 | 47 |
| Withdrew: Adverse event | 1 | 0 | 1 | 4 |
| Withdrew: Physician decision | 0 | 0 | 0 | 2 |
| Withdrew: Disease progressing | 3 | 4 | 2 | 31 |
| Withdrew: Miscellaneous | 2 | 4 | 3 | 10 |
DLTs were defined as a Grade 4 hematologic adverse events (AEs), Grade ≥ 3 non-hematologic AEs that were considered related to the study drug and that did not resolve within 14 days following presentation with standard management and care, Grade ≥ 3 thrombocytopenia with bleeding, neutropenic fever, any death not clearly due to the underlying disease or extraneous causes, or any change in liver function that met Hy's Law criteria of a DLT.
| Participants | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 |
|---|---|---|---|
| Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | 1 | 1 | 3 |
AEs were defined as any untoward medical occurrence associated with the use of a drug in humans. TEAEs are defined as any AE that started on or after the first day of study treatment and within 30 days of the last administration of study treatment, or that worsened on or after the first day of study treatment. AE severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 on a scale from Grade 1 (mild) to Grade 5 (death). An AE was considered "serious" if it resulted in death, life-threatening AE, hospitalization or prolongation of hospitalization, persistent or significant incapacity, or congenital anomaly/birth defect. The Investigator determined relatedness to the use of onvansertib. Clinically significant changes in vital signs, laboratory parameters, electrocardiograms, physical examinations, weight, and Eastern Cooperative Oncology Group (ECOG) performance status were reported as AEs.
| Participants | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 |
|---|---|---|---|
| Any TEAE | 9 | 7 | 6 |
| Any TEAE Related to Onvansertib | 8 | 7 | 4 |
| Any TEAE CTCAE Grade ≥3 | 7 | 6 | 4 |
| Any TEAE CTCAE Grade ≥3 Related to Onvansertib | 4 | 1 | 1 |
| Any Serious TEAE | 2 | 3 | 1 |
| Any Serious TEAE Related to Onvansertib | 0 | 0 | 0 |
ORR was defined as the percentage of participants documented to have a confirmed complete response (CR) or partial response (PR) using the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1). Two-sided 95% confidence interval (CI) was calculated using the exact binomial Clopper-Pearson method. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
| percentage of participants | Phase 1b: Onvansertib 15 mg/m^2 | Phase 2 Part 1: Onvansertib 15 mg/m^2 | Phase 2 Part 2: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| All-Treated Analysis Set: Objective Response Rate (ORR) | 42.9 (9.9 to 81.6) | 27.3 (13.3 to 45.5) | 15.4 (1.9 to 45.4) | 26.4 (15.3 to 40.3) |
AEs were defined as any untoward medical occurrence associated with the use of a drug in humans. TEAEs are defined as any AE that started on or after the first day of study treatment and within 30 days of the last administration of study treatment, or that worsened on or after the first day of study treatment. AE severity was graded according to the CTCAE version 5.0 on a scale from Grade 1 (mild) to Grade 5 (death). An AE was considered "serious" if it resulted in death, life-threatening AE, hospitalization or prolongation of hospitalization, persistent or significant incapacity, or congenital anomaly/birth defect. The Investigator determined relatedness to the use of onvansertib. Clinically significant changes in vital signs, laboratory parameters, electrocardiograms, physical examinations, weight, and ECOG performance status were reported as AEs.
| Participants | Phase 2: Onvansertib 15 mg/m^2 |
|---|---|
| Any TEAE | 46 |
| Any TEAE Related to Onvansertib | 26 |
| Any TEAE CTCAE Grade ≥3 | 32 |
| Any TEAE CTCAE Grade ≥3 Related to Onvansertib | 8 |
| Any Serious TEAE | 17 |
| Any Serious TEAE Related to Onvansertib | 1 |
DCR was defined as the percentage of participants documented to have a confirmed CR, PR or stable disease (SD) using the RECIST v1.1. Two-sided 95% CI was calculated using the exact binomial Clopper-Pearson method. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
| percentage of participants | Phase 1b: Onvansertib 15 mg/m^2 | Phase 2 Part 1: Onvansertib 15 mg/m^2 | Phase 2 Part 2: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| All-Treated Analysis Set: Disease Control Rate (DCR) | 100 (59.0 to 100.0) | 90.9 (75.7 to 98.1) | 92.3 (64.0 to 99.8) | 92.5 (81.8 to 97.9) |
PFS was defined as the time in months from the date of first administration of study treatment until the first observation of PD or death due to any cause, whichever occurs first, i.e.: (date of first PD or death date of first administration of study treatment +1)/30.4375. Median and 95% CI were calculated using the Kaplan-Meier method. Participants who did not have an observed documented PD or death from any cause were censored at the latest tumor response assessment date. PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
| months | Phase 1b: Onvansertib 15 mg/m^2 | Phase 2 Part 1: Onvansertib 15 mg/m^2 | Phase 2 Part 2: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| All-Treated Analysis Set: Progression-free Survival (PFS) | 18 (3.7 to NA) | 6 (5.6 to 11.1) | 8 (3.9 to NA) | 8 (5.8 to 13.5) |
DoR was calculated as the (date of first documented tumor progression or death due to any cause minus date of first documentation of a subsequently confirmed objective response plus 1)/30.4375. Participants who did not have an observed documented PD or death from any cause were censored at the latest tumor response assessment date.
| months | Phase 1b: Onvansertib 15 mg/m^2 | Phase 2 Part 1: Onvansertib 15 mg/m^2 | Phase 2 Part 2: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| All-Treated Analysis Set: Duration of Response (DoR) | 12 (NA to NA) | 12 (3.8 to NA) | NA (NA to NA) | 12 (7.5 to NA) |
OS was defined as the time in months from the date of first administration of study treatment until death due to any cause, i.e.: (Date of death date of first administration of study treatment +1)/30.4375. Participants who did not have documented death from any cause were censored at the date they were last known to be alive. OS was added as an endpoint with Protocol Amendment #1, therefore, OS data was only collected from then onward.
| months | Phase 1b: Onvansertib 15 mg/m^2 | Phase 2 Part 1: Onvansertib 15 mg/m^2 | Phase 2 Part 2: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| All-Treated Analysis Set: Overall Survival (OS) | NA (NA to NA) | NA (19.7 to NA) | NA (14.4 to NA) | NA (19.7 to NA) |
Blood samples were analyzed for the presence of circulating tumor DNA (ctDNA \[including KRAS mutations\]). KRAS-mutant allelic burden was based on liquid biopsies.
| percentage change in MAF | Phase 1b: Onvansertib 15 mg/m^2 | Phase 2 Part 1: Onvansertib 15 mg/m^2 | Phase 2 Part 2: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| All-Treated Analysis Set: Percentage Change in KRAS-mutant Allelic Fraction (MAF) | -85.5857 ± 19.44200 | -76.2323 ± 26.43313 | -62.0000 ± 33.72414 | -74.9000 ± 27.45740 |
Plasma pharmacokinetic (PK) parameters for onvansertib were estimated using non-compartmental methods.
| ng/mL | Phase 2: Onvansertib 15 mg/m^2 |
|---|---|
| Cycle 1 Day 1 | 0.0000 ± 0.0000 |
| Cycle 3 Day 1 | 0.3406 ± 0.34496 |
ORR was defined as the percentage of participants documented to have a confirmed CR or PR using the RECIST v1.1. Two-sided 95% CI was calculated using the exact binomial Clopper-Pearson method. Data are presented by bevacizumab used in first-line treatment yes versus no. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
| percentage of participants | Phase 1b; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 1b; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 1; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 1; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 2; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 2; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| All-Treated Analysis Set: ORR by Bevacizumab Used in First-line Treatment | 42.9 (9.9 to 81.6) | — | 4.5 (0.1 to 22.8) | 72.7 (39.0 to 94.0) | 0 (0.0 to 28.5) | 100 (15.8 to 100.0) | 10.0 (2.8 to 23.7) | 76.9 (46.2 to 95.0) |
PFS was defined as the time in months from the date of first administration of study treatment until the first observation of PD or death due to any cause, whichever occurs first, i.e.: (date of first PD or death date of first administration of study treatment +1)/30.4375. Median and 95% CI were calculated using the Kaplan-Meier method. Participants who did not have an observed documented PD or death from any cause were censored at the latest tumor response assessment date. Data are presented by bevacizumab used in first-line treatment yes versus no. PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
| percentage of participants | Phase 1b; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 1b; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 1; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 1; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 2; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 2 Part 2; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total; Bevacizumab Used in First-line Treatment: Onvansertib 15 mg/m^2 | Phase 1b and 2 Total; Bevacizumab Not Used in First-line Treatment: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| All-Treated Analysis Set: PFS by Bevacizumab Used in First-line Treatment | 18 (3.7 to NA) | — | 6 (3.6 to 6.1) | 15 (9.5 to NA) | 8 (3.7 to NA) | NA (NA to NA) | 6 (5.3 to 8.4) | 15 (9.5 to NA) |
Collected over Up to a maximum of 131 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1b: Onvansertib 12 mg/m^2 | 0/9 (0%) | 2/9 (22.2%) | 9/9 (100%) |
| Phase 1b: Onvansertib 15 mg/m^2 | 0/7 (0%) | 3/7 (42.9%) | 7/7 (100%) |
| Phase 1b: Onvansertib 18 mg/m^2 | 0/6 (0%) | 1/6 (16.7%) | 6/6 (100%) |
| Phase 2: Onvansertib 15 mg/m^2 | 1/46 (2.2%) | 17/46 (37%) | 46/46 (100%) |
| Event | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| Intestinal obstructionGastrointestinal disorders | 0/9 | 0/7 | 1/6 | 0/46 |
| DiarrhoeaGastrointestinal disorders | 0/9 | 1/7 | 0/6 | 1/46 |
| Liver abscessInfections and infestations | 0/9 | 1/7 | 0/6 | 0/46 |
| SepsisInfections and infestations | 0/9 | 1/7 | 0/6 | 0/46 |
| NauseaGastrointestinal disorders | 1/9 | 0/7 | 0/6 | 2/46 |
| Abdominal painGastrointestinal disorders | 1/9 | 0/7 | 0/6 | 1/46 |
| Abdominal abscessInfections and infestations | 1/9 | 0/7 | 0/6 | 0/46 |
| Hepatitis BInfections and infestations | 1/9 | 0/7 | 0/6 | 0/46 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/9 | 0/7 | 0/6 | 0/46 |
| Alanine aminotransferase increasedInvestigations | 1/9 | 0/7 | 0/6 | 0/46 |
| Event | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 |
|---|---|---|---|---|
| FatigueGeneral disorders | 8/9 | 7/7 | 4/6 | 36/46 |
| NauseaGastrointestinal disorders | 6/9 | 6/7 | 5/6 | 29/46 |
| DiarrhoeaGastrointestinal disorders | 6/9 | 6/7 | 3/6 | 23/46 |
| StomatitisGastrointestinal disorders | 4/9 | 6/7 | 1/6 | 18/46 |
| Neutrophil count decreasedInvestigations | 4/9 | 3/7 | 5/6 | 18/46 |
| White blood cell count decreasedInvestigations | 5/9 | 2/7 | 5/6 | 13/46 |
| AnaemiaBlood and lymphatic system disorders | 5/9 | 2/7 | 4/6 | 18/46 |
| Abdominal painGastrointestinal disorders | 2/9 | 4/7 | 3/6 | 16/46 |
| VomitingGastrointestinal disorders | 3/9 | 4/7 | 2/6 | 11/46 |
| PyrexiaGeneral disorders | 1/9 | 4/7 | 0/6 | 5/46 |
Safety Analysis Set: defined as participants who received at least one dose of onvansertib in any cycle. Three participants enrolled in 15 mg/m\^2 (2 in Phase 2 and 1 in Phase 1b) were inadvertently dosed at 12 mg/m\^2 and are represented under Phase 1b 12 mg/m\^2, as pre-specified in statistical analysis plan (SAP) section 9.4.
| Age, Continuous(years) | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 | Total |
|---|---|---|---|---|---|
| Mean | 60.3 ± 10.75 | 59.0 ± 14.39 | 57.5 ± 16.93 | 55.0 ± 9.82 | 56.3 ± 11.08 |
| Sex: Female, Male(Participants) | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 | Total |
|---|---|---|---|---|---|
| Female | 2 | 7 | 3 | 19 | 31 |
| Male | 7 | 0 | 3 | 27 | 37 |
| Ethnicity (NIH/OMB)(Participants) | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 1 | 6 | 7 |
| Not Hispanic or Latino | 8 | 7 | 5 | 39 | 59 |
| Unknown or Not Reported | 1 | 0 | 0 | 1 | 2 |
| Race/Ethnicity, Customized(Participants) | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 | Total |
|---|---|---|---|---|---|
| White | 6 | 6 | 4 | 38 | 54 |
| Black or African American | 0 | 0 | 0 | 3 | 3 |
| Asian | 2 | 0 | 2 | 3 | 7 |
| American Indian or Alaska Native | 0 | 1 | 0 | 0 | 1 |
| Other | 1 | 0 | 0 | 1 | 2 |
| Not Reported | 0 | 0 | 0 | 1 | 1 |
| Body Surface Area(m^2) | Phase 1b: Onvansertib 12 mg/m^2 | Phase 1b: Onvansertib 15 mg/m^2 | Phase 1b: Onvansertib 18 mg/m^2 | Phase 2: Onvansertib 15 mg/m^2 | Total |
|---|---|---|---|---|---|
| Mean | 1.99 ± 0.315 | 1.82 ± 0.293 | 2.02 ± 0.316 | 1.97 ± 0.264 | 1.96 ± 0.277 |
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Studies of the drugs tested here: Onvansertib · Bevacizumab
Cardiff Oncology