A Phase 3 interventional study of Ipatasertib and Paclitaxel in Breast Cancer, sponsored by Hoffmann-La Roche. Completed at 176 sites in 30 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
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Among 16 studies testing ipatasertib in Breast Neoplasms — 1 open to participants now, 5 under way, 1 of them phase 3. ipatasertib · Breast Neoplasms.
Among the 16 studies testing ipatasertib in Breast Neoplasms, this one is the 3rd largest by enrollment, is one of 3 that started in 2018, is one of 3 in phase 3, and was the 6th registered.
14,832 studies on the registry are indexed under Breast Neoplasms; 3,320 are open to participants now.
Browse Breast Neoplasms studies →1 of the 16 studies testing ipatasertib in Breast Neoplasms is open now, in 9 countries. Recruiting first, the newest first:
Hoffmann-La Roche · Sites in United States, Australia, France and 6 more countries
Ages 18+
By country, each count listing its studies:
No approval found in the FDA or EMA files read. How studies give it is on its page →
Of the 2,399 Breast Neoplasms studies recruiting now, 1,570 (65%) set no upper age limit and 592 (25%) stop at 75 or younger; 103 take children under 18; 215 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
On this site’s reading of the record, ipatasertib is the treatment under test here. Read study by study →
16 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 7 · Phase 2 8 · Phase 3 3
First in 2014; this study’s year is marked. 3 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 579 is above the median of 72 across 10,903 interventional studies indexed under Breast Neoplasms.
Median enrollment 132 across the 16 interventional studies. Of the 11 that completed or were terminated, 8 (73%) have results posted.
This tab as a report to print or save as PDF → With an account.
9 of 16 have an industry lead sponsor. The 9 most frequent:
Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 88 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
229 studies in Breast Neoplasms by Hoffmann-La Roche: 16 open now, 28 under way, 13 of them phase 3. Of 193 finished, 120 (62%) have results posted.
Among the 229 studies in Breast Neoplasms by Hoffmann-La Roche, this one is the 29th largest by enrollment of the 170 interventional ones that give a count, is one of 8 that started in 2018, is one of 61 in phase 3, and was the 181st registered.
Hoffmann-La Roche’s Breast Neoplasms studies by the year they started, since 1998.
1 of the studies testing ipatasertib in Breast Neoplasms that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04920708Royal Marsden NHS Foundation TrustFulvestrant, Ipatasertib and CDK4/6 Inhibition in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression | 2027-06 |
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Among the 16 studies testing ipatasertib in Breast Neoplasms, from their registry updates:
Among Hoffmann-La Roche’s 229 in Breast Neoplasms:
This tab as a report to print or save as PDF → With an account.
This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) breast adenocarcinoma who are not suitable for endocrine therapy.
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.
Exclusion Criteria:
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.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
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.
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.
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.
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.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
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.
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 share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
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.
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.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
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.
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.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
Drug: Ipatasertib · Drug: Paclitaxel
Drug: Paclitaxel · Drug: Placebo
Ipatasertib, 400 milligrams (mg), administered orally once a day (QD) on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Paclitaxel, 80 mg/square meter (m\^2), administered intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Matching placebo, administered orally QD on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Cohort A: Progression-Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
Time frame: From randomization up to 27 months
Cohort B: PFS
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.
Time frame: From randomization up to 24.4 months
Cohort C: PFS
PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From enrollment up to 31 months
Cohort A and B: Objective Response Rate (ORR)
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Time frame: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Cohort C: ORR
ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Time frame: From enrollment up to 31 months
Cohort A and B: Duration of Response (DOR)
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Cohort C: DOR
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From enrollment up to 31 months
Cohort A and B: Clinical Benefit Rate (CBR)
CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Time frame: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Cohort C: CBR
CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Time frame: From enrollment up to 31 months
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
Time frame: From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)
Cohort B: Time to Deterioration (TTD) in Pain
Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed ≥ 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.
Time frame: Baseline up to 24.4 months
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Time frame: Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Number of Participants With at Least One Adverse Events of Special Interest (AESI)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade \>= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade \>= 2 colitis/enterocolitis.
Time frame: Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Cohorts A and B:Plasma Concentration of Ipatasertib
Time frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Cohort C: Plasma Concentration of Ipatasertib
Time frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Cohorts A and B: Plasma Concentration of G-037720
G-037720 was a metabolite of ipatasertib.
Time frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Cohort C: Plasma Concentration of G-037720
G-037720 was a metabolite of ipatasertib.
Time frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Cohort C: 1-year Event-free PFS Rate
PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Time frame: From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year
Cohort C: 1-year Event-free OS Rate
OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.
Time frame: From enrollment up to death from any cause, up to 1 year
Cohort C: Serum Concentration of Atezolizumab
As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Time frame: Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)
Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Time frame: Up to 45.5 months
Participants with protocol specified triple-negative breast cancer (TNBC) or HR+/HER- took part in the study in the following countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, Costa Rica, Czech Republic, France, Greece, Germany, Hungary, Italy, India, Japan, Macedonia, Mexico, Poland, Peru, Republic of Korea, Russian Federation, Slovenia, Spain, Singapore, South Africa, Taiwan, Turkey, Ukraine, United Kingdom, and United States from 6 January 2018 to 4 January 2023.
| Milestone | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Started | 87 | 168 | 76 | 146 | 102 |
| Safety evaluable population | 87 | 166 | 75 | 145 | 102 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 87 | 168 | 76 | 146 | 102 |
| Withdrew: Reason not specified | 12 | 21 | 9 | 9 | 29 |
| Withdrew: Withdrawal by subject | 13 | 15 | 4 | 15 | 6 |
| Withdrew: Protocol deviation | 0 | 1 | 1 | 1 | 0 |
| Withdrew: Adverse event | 1 | 1 | 0 | 1 | 0 |
| Withdrew: Death | 40 | 89 | 43 | 76 | 50 |
| Withdrew: Lost to follow-up | 5 | 5 | 4 | 7 | 4 |
| Withdrew: Physician decision | 16 | 34 | 14 | 34 | 13 |
| Withdrew: Progressive disease | 0 | 2 | 1 | 2 | 0 |
| Withdrew: Symptomatic deterioration | 0 | 0 | 0 | 1 | 0 |
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
| months | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel |
|---|---|---|
| Cohort A: Progression-Free Survival (PFS) | 6.1 (5.5 to 9.0) | 7.4 (5.6 to 8.5) |
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.
| months | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|
| Cohort B: PFS | 9.3 (7.2 to 12.2) | 9.3 (8.0 to 11.0) |
PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
| months | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: PFS | 7.1 (5.5 to 9.1) |
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
| percentage of participants | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|---|---|
| Cohort A and B: Objective Response Rate (ORR) | 34.9 (24.92 to 45.92) | 38.9 (31.49 to 46.76) | 46.7 (35.05 to 58.55) | 46.5 (38.18 to 55.02) |
ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
| percentage of participants | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: ORR | 52.9 (42.80 to 62.90) |
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
| months | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|---|---|
| Cohort A and B: Duration of Response (DOR) | 16.6 (4.9 to NA) | 9.4 (7.3 to 11.1) | 9.2 (6.8 to 12.5) | 9.2 (7.2 to 11.3) |
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
| months | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: DOR | 8.7 (5.7 to 12.7) |
CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
| percentage of participants | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|---|---|
| Cohort A and B: Clinical Benefit Rate (CBR) | 45.3 (34.58 to 56.45) | 46.7 (38.96 to 54.57) | 65.3 (53.46 to 75.96) | 68.8 (60.50 to 76.21) |
CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
| percentage of participants | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: CBR | 54.9 (44.74 to 64.78) |
OS was defined as the time from randomization to death from any cause.
| months | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Overall Survival (OS) | 24.9 (16.9 to 40.4) | 24.2 (19.2 to 29.4) | 28.4 (20.6 to 37.3) | 29.0 (22.4 to 34.8) | 22.8 (17.8 to NA) |
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
| score on scale | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|---|---|
| Day 1 Cycle 2 | 0.95 ± 20.59 | -0.26 ± 24.58 | 4.79 ± 15.83 | -3.61 ± 21.45 |
| Day 1 Cycle 3 | -0.93 ± 20.53 | 0.35 ± 21.73 | 1.19 ± 19.62 | -2.13 ± 17.99 |
| Day 1 Cycle 4 | -4.44 ± 19.42 | -2.42 ± 21.95 | -0.79 ± 21.10 | -1.99 ± 20.75 |
| Day 1 Cycle 5 | -2.08 ± 16.46 | -2.87 ± 18.61 | -1.19 ± 20.00 | -3.01 ± 18.70 |
| Day 1 Cycle 6 | -6.94 ± 15.97 | -2.06 ± 21.04 | 1.42 ± 19.18 | -3.88 ± 20.67 |
| Day 1 Cycle 7 | -5.48 ± 12.45 | -3.28 ± 20.93 | 0.34 ± 20.34 | -4.17 ± 19.47 |
| Day 1 Cycle 8 | -6.90 ± 13.56 | 0.33 ± 22.11 | 0.35 ± 16.84 | -5.99 ± 18.55 |
| Day 1 Cycle 9 | 0.00 ± 10.29 | -3.49 ± 25.28 | 1.10 ± 18.80 | -7.37 ± 20.05 |
| Day 1 Cycle 10 | -2.38 ± 9.91 | -4.52 ± 21.61 | 1.28 ± 19.64 | -6.43 ± 18.83 |
| Day 1 Cycle 11 | -3.43 ± 15.88 | -4.46 ± 21.09 | 2.38 ± 22.83 | -5.13 ± 19.30 |
| Day 1 Cycle 12 | 0.76 ± 11.46 | -8.33 ± 19.94 | 0.00 ± 22.46 | -4.02 ± 16.32 |
| Day 1 Cycle 13 | -5.21 ± 10.85 | -8.33 ± 23.57 | -2.43 ± 21.63 | -4.65 ± 18.57 |
| Day 1 Cycle 14 | -2.38 ± 10.45 | -3.57 ± 19.26 | -0.76 ± 21.81 | -3.29 ± 15.68 |
| Day 1 Cycle 15 | -9.72 ± 11.08 | -5.77 ± 12.90 | -2.22 ± 18.49 | -0.62 ± 20.14 |
| Day 1 Cycle 16 | -6.67 ± 13.69 | -8.33 ± 14.91 | -4.17 ± 19.27 | -2.33 ± 16.05 |
| Day 1 Cycle 17 | -8.33 ± 9.62 | -6.82 ± 13.34 | -7.64 ± 15.27 | -5.95 ± 13.73 |
| Day 1 Cycle 18 | -8.33 ± 9.62 | -15.48 ± 16.96 | -9.26 ± 19.74 | -6.55 ± 16.07 |
| Day 1 Cycle 19 | -4.17 ± 8.33 | -20.00 ± 7.45 | -11.67 ± 16.24 | -7.64 ± 23.96 |
| Day 1 Cycle 20 | -8.33 ± 11.79 | -5.56 ± 9.62 | -16.67 ± 11.79 | -10.00 ± 12.30 |
| Day 1 Cycle 21 | -16.67 ± NA | -16.67 ± 0.00 | -13.89 ± 20.97 | -10.71 ± 13.36 |
| Day 1 Cycle 22 | -16.67 ± NA | -16.67 ± NA | -11.11 ± 9.62 | -14.29 ± 15.00 |
| Day 1 Cycle 23 | -16.67 ± NA | -25.00 ± NA | -16.67 ± 16.67 | -15.00 ± 18.07 |
| Day 1 Cycle 24 | -16.67 ± NA | -41.67 ± NA | -16.67 ± 0.00 | -16.67 ± 11.79 |
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
| score on scale | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Day 1 Cycle 2 | -0.42 ± 18.02 |
| Day 1 Cycle 3 | 0.18 ± 18.32 |
| Day 1 Cycle 4 | -4.37 ± 22.83 |
| Day 1 Cycle 5 | -6.41 ± 20.19 |
| Day 1 Cycle 6 | -7.10 ± 21.24 |
| Day 1 Cycle 7 | -5.09 ± 18.20 |
| Day 1 Cycle 8 | -4.83 ± 21.24 |
| Day 1 Cycle 9 | -7.66 ± 23.68 |
| Day 1 Cycle 10 | -7.07 ± 18.76 |
| Day 1 Cycle 11 | -6.00 ± 19.02 |
| Day 1 Cycle 12 | -2.90 ± 18.57 |
| Day 1 Cycle 13 | -1.45 ± 19.08 |
| Day 1 Cycle 14 | -7.89 ± 21.24 |
| Day 1 Cycle 15 | -5.09 ± 26.37 |
| Day 1 Cycle 16 | -11.98 ± 27.55 |
| Day 1 Cycle 17 | -10.90 ± 32.16 |
| Day 1 Cycle 18 | -3.85 ± 20.30 |
| Day 1 Cycle 19 | -3.21 ± 25.35 |
| Day 1 Cycle 20 | -3.21 ± 24.89 |
| Day 1 Cycle 21 | -2.56 ± 24.86 |
| Day 1 Cycle 22 | -12.18 ± 32.92 |
| Day 1 Cycle 23 | 3.03 ± 24.23 |
| Day 1 Cycle 24 | 3.79 ± 24.54 |
| Day 1 Cycle 25 | -4.63 ± 21.29 |
| Day 1 Cycle 26 | -0.83 ± 19.82 |
| Day 1 Cycle 27 | 2.08 ± 26.63 |
| Day 1 Cycle 28 | 1.39 ± 23.81 |
| Day 1 Cycle 29 | -1.19 ± 28.64 |
| Day 1 Cycle 30 | 3.33 ± 24.01 |
| Day 1 Cycle 31 | 22.22 ± 12.73 |
| Day 1 Cycle 32 | 10.42 ± 23.94 |
| Day 1 Cycle 33 | 16.67 ± 22.05 |
| Day 1 Cycle 34 | 16.67 ± 30.05 |
| Day 1 Cycle 35 | 13.89 ± 17.35 |
| Day 1 Cycle 36 | 20.83 ± 29.46 |
| Day 1 Cycle 37 | 16.67 ± 23.57 |
| Day 1 Cycle 38 | 16.67 ± 23.57 |
| Day 1 Cycle 39 | 25.00 ± 35.36 |
| Day 1 Cycle 40 | 33.33 ± NA |
| Day 1 Cycle 41 | 50.00 ± NA |
| Day 1 Cycle 42 | 41.67 ± NA |
| Day 1 Cycle 43 | 41.67 ± NA |
| Day 1 Cycle 44 | 50.00 ± NA |
Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed ≥ 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.
| months | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|
| Cohort B: Time to Deterioration (TTD) in Pain | NA (NA to NA) | NA (11.1 to NA) |
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
| Participants | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Number of Participants With Adverse Events (AEs) | 84 | 162 | 74 | 144 | 102 |
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade \>= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade \>= 2 colitis/enterocolitis.
| Participants | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Number of Participants With at Least One Adverse Events of Special Interest (AESI) | 79 | 157 | 73 | 141 | 101 |
| nanograms per milliliter (ng/mL) | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|
| Cycle 1 Day 1 | 176 ± 232 | 165 ± 326 |
| Cycle 1 Day 15 | 191 ± 184 | 211 ± 216 |
| Cycle 3 Day 15 | 165 ± 169 | 234 ± 149 |
| ng/mL | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cycle 1 Day 1 | 175 ± 183 |
| Cycle 1 Day 15 | 233 ± 161.6 |
| Cycle 3 Day 15 | 207 ± 197.6 |
G-037720 was a metabolite of ipatasertib.
| ng/mL | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel |
|---|---|---|
| Cycle 1 Day 1 | 45.6 ± 777 | 68.2 ± 405 |
| Cycle 1 Day 15 | 83.9 ± 183 | 95.1 ± 211 |
| Cycle 3 Day 15 | 90.8 ± 180 | 109 ± 169 |
G-037720 was a metabolite of ipatasertib.
| ng/mL | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cycle 1 Day 1 | 67.3 ± 222.3 |
| Cycle 1 Day 15 | 96.8 ± 140.7 |
| Cycle 3 Day 15 | 96.5 ± 167.9 |
PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
| percentage of participants | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: 1-year Event-free PFS Rate | 31.17 (21.59 to 40.76) |
OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.
| percentage of participants | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: 1-year Event-free OS Rate | 79.38 (71.31 to 87.44) |
As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
| micrograms per milliliter (µg/mL) | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Day 1 Cycle 1 | 309 ± 31.7 |
| Day 15 Cycle 1 | 91.5 ± 23.9 |
| Day 1 Cycle 2 | 130 ± 54.1 |
| Day 1 Cycle 3 | 200 ± 41.1 |
| Day 1 Cycle 4 | 231 ± 52.3 |
| Day 1 Cycle 8 | 327 ± 27.6 |
| Day 1 Cycle 12 | 371 ± 30.5 |
| Day 1 Cycle 16 | 402 ± 42.4 |
The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
| Participants | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|
| Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab | 18 |
Collected over Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| COHORT A Placebo + Paclitaxel | 41/87 (47.1%) | 20/87 (23%) | 82/87 (94.3%) |
| COHORT A Ipatasertib + Paclitaxel | 91/168 (54.2%) | 34/166 (20.5%) | 161/166 (97%) |
| COHORT B Placebo + Paclitaxel | 44/76 (57.9%) | 11/75 (14.7%) | 72/75 (96%) |
| COHORT B Ipatasertib + Paclitaxel | 78/146 (53.4%) | 30/145 (20.7%) | 141/145 (97.2%) |
| COHORT C Ipatasertib + Atezolizumab + Paclitaxel | 50/102 (49%) | 29/102 (28.4%) | 101/102 (99%) |
| Event | COHORT A Placebo + Paclitaxel | COHORT A Ipatasertib + Paclitaxel | COHORT B Placebo + Paclitaxel | COHORT B Ipatasertib + Paclitaxel | COHORT C Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 4/87 | 2/166 | 1/75 | 2/145 | 3/102 |
| DiarrhoeaGastrointestinal disorders | 0/87 | 6/166 | 1/75 | 4/145 | 4/102 |
| PyrexiaGeneral disorders | 0/87 | 0/166 | 0/75 | 0/145 | 4/102 |
| Urinary tract infectionInfections and infestations | 0/87 | 1/166 | 1/75 | 0/145 | 3/102 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 2/87 | 1/166 | 0/75 | 1/145 | 1/102 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/87 | 3/166 | 0/75 | 2/145 | 2/102 |
| VomitingGastrointestinal disorders | 0/87 | 2/166 | 0/75 | 0/145 | 2/102 |
| FatigueGeneral disorders | 0/87 | 1/166 | 1/75 | 0/145 | 2/102 |
| CholecystitisHepatobiliary disorders | 0/87 | 0/166 | 0/75 | 0/145 | 2/102 |
| DehydrationMetabolism and nutrition disorders | 0/87 | 0/166 | 0/75 | 1/145 | 2/102 |
| Event | COHORT A Placebo + Paclitaxel | COHORT A Ipatasertib + Paclitaxel | COHORT B Placebo + Paclitaxel | COHORT B Ipatasertib + Paclitaxel | COHORT C Ipatasertib + Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 28/87 | 138/166 | 29/75 | 125/145 | 86/102 |
| AlopeciaSkin and subcutaneous tissue disorders | 38/87 | 78/166 | 44/75 | 75/145 | 42/102 |
| NauseaGastrointestinal disorders | 22/87 | 66/166 | 17/75 | 60/145 | 42/102 |
| ConstipationGastrointestinal disorders | 31/87 | 49/166 | 26/75 | 42/145 | 13/102 |
| AnaemiaBlood and lymphatic system disorders | 23/87 | 43/166 | 15/75 | 45/145 | 34/102 |
| VomitingGastrointestinal disorders | 8/87 | 53/166 | 6/75 | 45/145 | 28/102 |
| Neuropathy peripheralNervous system disorders | 20/87 | 39/166 | 12/75 | 46/145 | 30/102 |
| Peripheral sensory neuropathyNervous system disorders | 19/87 | 32/166 | 23/75 | 23/145 | 8/102 |
| RashSkin and subcutaneous tissue disorders | 11/87 | 26/166 | 9/75 | 31/145 | 29/102 |
| FatigueGeneral disorders | 15/87 | 30/166 | 19/75 | 29/145 | 23/102 |
Intention-to-treat (ITT) Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C.
| Age, Continuous(years) | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| Mean | 54.2 ± 12.6 | 54.6 ± 12.8 | 54.5 ± 11.3 | 57.2 ± 11.1 | 54.6 ± 11.7 | 55.2 ± 12.0 |
| Sex: Female, Male(Participants) | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| Female | 87 | 167 | 76 | 144 | 102 | 576 |
| Male | 0 | 1 | 0 | 2 | 0 | 3 |
| Ethnicity (NIH/OMB)(Participants) | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 29 | 59 | 13 | 29 | 36 | 166 |
| Not Hispanic or Latino | 57 | 101 | 62 | 115 | 58 | 393 |
| Unknown or Not Reported | 1 | 8 | 1 | 2 | 8 | 20 |
| Race (NIH/OMB)(Participants) | Cohort A: Placebo + Paclitaxel | Cohort A: Ipatasertib + Paclitaxel | Cohort B: Placebo + Paclitaxel | Cohort B: Ipatasertib + Paclitaxel | Cohort C: Ipatasertib + Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 13 | 15 | 3 | 4 | 5 | 40 |
| Asian | 17 | 37 | 22 | 38 | 12 | 126 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 1 | 1 |
| Black or African American | 1 | 5 | 3 | 2 | 9 | 20 |
| White | 51 | 99 | 45 | 93 | 55 | 343 |
| More than one race | 0 | 4 | 2 | 0 | 5 | 11 |
| Unknown or Not Reported | 5 | 8 | 1 | 9 | 15 | 38 |
Showing the first 100 of 176 sites across 30 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jan 2018 to primary completion in Jan 2023, 59 months.
Results were first posted in Mar 2024, 1 year 2 months after primary completion.
Of 272 industry-sponsored phase 3 interventional studies under Breast Neoplasms, half reached primary completion within 40 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 63. This study's 59 months is above that.
Counting every sponsor, half of 600 studies reached it within 59 months; a quarter within 36 and three quarters within 96.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ipatasertib