A Phase 3 interventional study of Atezolizumab and Ipatasertib in Triple-Negative Breast Cancer, sponsored by Hoffmann-La Roche. Completed at 182 sites in 37 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-27.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
This study evaluated the efficacy and safety of ipatasertib in combination with atezolizumab and paclitaxel in locally advanced or metastatic Triple-Negative Breast Cancer (TNBC) previously untreated in this setting.
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Exclusion Criteria:
TNBC participants with programmed death-ligand 1 (PD-L1) non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m\^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.
Drug: Atezolizumab · Drug: Ipatasertib · Drug: Paclitaxel
TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Placebo for Atezolizumab
TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.
Drug: Paclitaxel · Drug: Placebo for Atezolizumab · Drug: Placebo for Ipatasertib
TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.
Drug: Atezolizumab · Drug: Ipatasertib · Drug: Paclitaxel
TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.
Drug: Atezolizumab · Drug: Paclitaxel · Drug: Placebo for Ipatasertib
Atezolizumab was administered as per the dosage regimen mentioned in arm descriptions.
Ipatasertib was administered as per the dosage regimen mentioned in arm descriptions.
Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.
Placebo was administered as per the dosage regimen mentioned in arm descriptions.
Placebo was administered as per the dosage regimen mentioned in arm descriptions.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from randomization to the first occurrence of disease progression as determined locally by RECIST or death from any cause during treatment, whichever occurs first.
Time frame: From Randomization to disease progression, study completion, or death (up to 39 months)
Overall Survival (OS)
OS was defined as the time from randomization to the time of death from any cause on study.
Time frame: From randomization up to study completion or death (Up to 39 months)
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Up to 39 months
Participants took part in the study at 215 investigative centers from 25 November 2019 to 28 February 2023.
| Milestone | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Started | 43 | 43 | 41 | 58 | 57 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 43 | 43 | 41 | 58 | 57 |
| Withdrew: Withdrawal by subject | 4 | 8 | 9 | 11 | 13 |
| Withdrew: Physician decision | 23 | 15 | 18 | 29 | 23 |
| Withdrew: Reason not specified | 0 | 1 | 0 | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 1 | 1 |
| Withdrew: Death | 16 | 19 | 13 | 17 | 18 |
PFS was defined as the time from randomization to the first occurrence of disease progression as determined locally by RECIST or death from any cause during treatment, whichever occurs first.
| months | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 7.1 (5.1 to 9.3) | 5.6 (3.7 to 8.2) | 3.7 (3.6 to 5.4) | 5.6 (5.4 to 9.2) | 5.7 (4.0 to 9.1) |
OS was defined as the time from randomization to the time of death from any cause on study.
| months | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Overall Survival (OS) | 15.7 (12.5 to NA) | 15.3 (15.3 to NA) | 16.6 (9.6 to NA) | NA (14.1 to NA) | 17.2 (13.4 to NA) |
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
| Participants | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| Number of Participants With Adverse Events (AEs) | 42 | 43 | 40 | 58 | 56 |
Collected over Up to 39 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | 16/43 (37.2%) | 14/43 (32.6%) | 42/43 (97.7%) |
| Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | 19/43 (44.2%) | 7/43 (16.3%) | 42/43 (97.7%) |
| Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | 13/41 (31.7%) | 7/41 (17.1%) | 40/41 (97.6%) |
| Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxe | 18/58 (31%) | 16/58 (27.6%) | 56/58 (96.6%) |
| Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel | 18/57 (31.6%) | 9/57 (15.8%) | 55/57 (96.5%) |
| Event | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxe | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| RashSkin and subcutaneous tissue disorders | 3/43 | 1/43 | 0/41 | 1/58 | 0/57 |
| COVID-19Infections and infestations | 0/43 | 1/43 | 2/41 | 0/58 | 0/57 |
| DiarrhoeaGastrointestinal disorders | 2/43 | 1/43 | 0/41 | 1/58 | 0/57 |
| CellulitisInfections and infestations | 2/43 | 0/43 | 0/41 | 0/58 | 0/57 |
| Septic shockInfections and infestations | 2/43 | 0/43 | 0/41 | 0/58 | 0/57 |
| NeutropeniaBlood and lymphatic system disorders | 0/43 | 0/43 | 0/41 | 2/58 | 0/57 |
| Alanine aminotransferase increasedInvestigations | 1/43 | 0/43 | 0/41 | 2/58 | 0/57 |
| Aspartate aminotransferase increasedInvestigations | 1/43 | 0/43 | 0/41 | 2/58 | 0/57 |
| Clostridium colitisInfections and infestations | 0/43 | 0/43 | 1/41 | 0/58 | 0/57 |
| Diarrhoea infectiousInfections and infestations | 0/43 | 0/43 | 1/41 | 0/58 | 0/57 |
| Event | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxe | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel |
|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 32/43 | 30/43 | 15/41 | 37/58 | 16/57 |
| ConstipationGastrointestinal disorders | 7/43 | 12/43 | 26/41 | 16/58 | 24/57 |
| AlopeciaSkin and subcutaneous tissue disorders | 10/43 | 13/43 | 19/41 | 18/58 | 25/57 |
| NauseaGastrointestinal disorders | 17/43 | 14/43 | 9/41 | 22/58 | 13/57 |
| AnaemiaBlood and lymphatic system disorders | 15/43 | 7/43 | 6/41 | 22/58 | 12/57 |
| NeutropeniaBlood and lymphatic system disorders | 15/43 | 5/43 | 8/41 | 11/58 | 9/57 |
| Neuropathy peripheralNervous system disorders | 15/43 | 8/43 | 10/41 | 8/58 | 8/57 |
| RashSkin and subcutaneous tissue disorders | 10/43 | 10/43 | 7/41 | 19/58 | 17/57 |
| Alanine aminotransferase increasedInvestigations | 11/43 | 11/43 | 12/41 | 12/58 | 11/57 |
| Decreased appetiteMetabolism and nutrition disorders | 6/43 | 6/43 | 6/41 | 16/58 | 7/57 |
Intent-to-treat (ITT) population included all participants randomized in this study.
| Age, Continuous(years) | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| Mean | 55.5 ± 11.7 | 50.8 ± 11.6 | 53.5 ± 10.7 | 53.7 ± 12.1 | 51.1 ± 11.7 | 52.9 ± 11.7 |
| Sex/Gender, Customized(Participants) | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| Female | 43 | 43 | 41 | 58 | 57 | 242 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 8 | 9 | 6 | 15 | 14 | 52 |
| Not Hispanic or Latino | 32 | 32 | 35 | 41 | 43 | 183 |
| Unknown or Not Reported | 3 | 2 | 0 | 2 | 0 | 7 |
| Race (NIH/OMB)(Participants) | Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 1 Arm B: Ipatasertib + Atezolizumab Matching Placebo + Paclitaxel | Cohort 1 Arm C: Ipatasertib Matching Placebo + Atezolizumab Matching Placebo + Paclitaxel | Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | Cohort 2 Arm B: Ipatasertib Matching Placebo+ Atezolizumab + Paclitaxel | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 5 | 3 | 1 | 5 | 6 | 20 |
| Asian | 10 | 7 | 9 | 19 | 16 | 61 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 0 | 2 | 2 | 8 |
| White | 26 | 29 | 29 | 29 | 32 | 145 |
| More than one race | 0 | 0 | 1 | 0 | 1 | 2 |
| Unknown or Not Reported | 0 | 2 | 1 | 3 | 0 | 6 |
Showing the first 100 of 182 sites across 37 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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