A Study to Evaluate the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer
A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Patients With Locally Advanced or Metastatic Triple-Negative Breast Cancer
2 other identifiers
interventional
139
5 countries
18
Brief Summary
This is a study consisting of four cohorts in this setting. In Cohort 1, the safety and efficacy of ipatasertib (ipat) in combination with atezolizumab (atezo) and paclitaxel (pac) or nab-paclitaxel will be evaluated for participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not previously received chemotherapy. In Cohort 2, ipatasertib and atezolizumab (with no chemotherapy), will be administered to participants with locally advanced or metastatic TNBC. In Cohort 3, the safety and efficacy of neoadjuvant ipatasertib, atezolizumab, doxorubicin and cyclophosphamide (AC) (Ipat + Atezo + AC) followed by Ipat + Atezo + Pac will be evaluated in participants with locally advanced Type 2-4 (T2-4) TNBC. In Cohort 4, the safety and efficacy of Ipat + Atezo + Pac will be evaluated in participants with PD-L1 (Programmed Death-Ligand-1) positive locally advanced or metastatic TNBC that is not amenable to resection and who have not previously received chemotherapy in the advanced setting.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 breast-cancer
Started Feb 2018
Typical duration for phase_1 breast-cancer
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 13, 2018
CompletedFirst Submitted
Initial submission to the registry
January 7, 2019
CompletedFirst Posted
Study publicly available on registry
January 11, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 16, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 16, 2022
CompletedResults Posted
Study results publicly available
October 30, 2024
CompletedOctober 30, 2024
August 1, 2024
4.1 years
January 7, 2019
March 15, 2023
August 12, 2024
Conditions
Outcome Measures
Primary Outcomes (3)
Cohort 1 and Cohort 4: Percentage of Participants With Objective Response (OR) as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version (v) 1.1
Objective Response Rate: percentage participants with confirmed complete response (CR) or partial response (PR) on 2 consecutive occasions \>or= 4 weeks apart, as determined by investigator according to RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Percentages have been rounded off. No participants were enrolled in cohort 4, hence no data reported.
From screening up to approximately 43.6 months
Cohort 3: Pathological Complete Response (pCR) Rate
pCR rate was defined as the percentage of participants who had no residual invasive disease in the breast and no residual disease in the lymph nodes (ypT0/Tis ypN0 in the current American Joint Committee on Cancer (AJCC )staging system) based on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant therapy.
2-6 weeks following last dose of study treatment (up to 69 weeks)
Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease are also considered as AEs. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). No participants were enrolled in cohort 3 Arm G and 4, and hence no data was reported.
Up until 90 days after the last dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to 4 years 1 month)
Secondary Outcomes (8)
Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1
From the date of first documented confirmed response (CR or PR) to disease progression or death due to any cause (up to approximately 43.6 months)
Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1
From enrollment up to disease progression or death due to any cause whichever occurs first (up to approximately 43.6 months)
Cohort 1 and Cohort 4: Overall Survival (OS)
From enrollment up to death due to any cause (up to approximately 43.6 months).
Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib
Day 15 Cycle 1: pre-dose and 1, 2, 4 and 6 hours post-dose, Day 15 Cycle2: predose and 1, 2, 4 and 6 hours post-dose and Day 15 Cycle 3 - post dose up to - 3 hours (each cycle is of 28 days)
Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720)
Day 15 Cycle 1 - pre-dose and 1 hour, 2 hours, 4 hours and 6 hours post-dose, Day 15 Cycle2: predose and 1 hour, 2 hours, 4 hours and 6 hours post-dose and Day 15 Cycle 3 - post dose up to - 3 hours (each cycle is of 28 days)
- +3 more secondary outcomes
Study Arms (15)
Arm A1: Ipat + Atezo + Pacl
EXPERIMENTALSafety Run-In (Cohort 1): Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by intravenous (IV) infusion on Days 1 and 15 of each 28 day cycle. Paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm A2: Ipat + Atezo + Pacl
EXPERIMENTALExpansion (Cohort 1): Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by intravenous (IV) infusion on Days 1 and 15 of each 28 day cycle. Paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm A3: Ipat + Atezo + Pacl
EXPERIMENTALExpansion (Cohort 1): Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by intravenous (IV) infusion on Days 1 and 15 of each 28 day cycle. Paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm B1: Ipat + Atezo + Nab-Pacl
EXPERIMENTALSafety Run-In (Cohort 1): Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by IV infusion on Days 1 and 15 of each 28 day cycle. Nab-paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm B2: Ipat + Atezo + Nab-Pacl
EXPERIMENTALExpansion (Cohort 1): Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by IV infusion on Days 1 and 15 of each 28 day cycle. Nab-paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm C1: (Ipat + Pacl) (2 weeks) + Atezo
EXPERIMENTALSafety Run-In (Cohort 1): Participants will receive a 2-week lead in of ipatasertib in combination with paclitaxel, followed by atezolizumab in an initial 28-day (1 cycle) period. Ipatasertib will be administered orally daily on Days 1-21, with paclitaxel administered by IV infusion on Days 1, 8 and 15. Atezolizumab will be administered by IV infusion on Day 15. In all subsequent treatment cycles, ipatasertib will be administered orally daily on Days 1-21, paclitaxel will be administered by IV infusion on Days 1, 8, and 15 and atezolizumab will be administered by IV infusion on Days 1 and 15. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm C2 (Ipat + Pacl) (2 weeks) + Atezo
EXPERIMENTALExpansion (Cohort 1): Participants will receive a 2-week lead in of ipatasertib in combination with paclitaxel, followed by atezolizumab in an initial 28-day (1 cycle) period. Ipatasertib will be administered orally daily on Days 1-21, with paclitaxel administered by IV infusion on Days 1, 8 and 15. Atezolizumab will be administered by IV infusion on Day 15. In all subsequent treatment cycles, ipatasertib will be administered orally daily on Days 1-21, paclitaxel will be administered by IV infusion on Days 1, 8, and 15 and atezolizumab will be administered by IV infusion on Days 1 and 15. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm D1: (Atezo + Pacl) (2 weeks) + Ipat
EXPERIMENTALSafety Run-In (Cohort 1): Participants will receive a 2-week lead in of atezolizumab in combination with paclitaxel, followed by ipatasertib in an initial 28-day (1 cycle) period. Atezolizumab will be administered via IV infusion on Days 1 and 15, with paclitaxel administered by IV infusion on Days 1, 8 and 15. Ipatasertib will be administered orally daily on Days 15-21. In all subsequent treatment cycles, ipatasertib will be administered orally daily on Days 1-21, paclitaxel will be administered by IV infusion on Days 1, 8, and 15 and atezolizumab will be administered by IV infusion on Days 1 and 15. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm D2: (Atezo + Pacl) (2 weeks) + Ipat
EXPERIMENTALExpansion (Cohort 1): Participants will receive a 2-week lead in of atezolizumab in combination with paclitaxel, followed by ipatasertib in an initial 28-day (1 cycle) period. Atezolizumab will be administered via IV infusion on Days 1 and 15, with paclitaxel administered by IV infusion on Days 1, 8 and 15. Ipatasertib will be administered orally daily on Days 15-21. In all subsequent treatment cycles, ipatasertib will be administered orally daily on Days 1-21, paclitaxel will be administered by IV infusion on Days 1, 8, and 15 and atezolizumab will be administered by IV infusion on Days 1 and 15. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm E: Ipat + Atezo
EXPERIMENTALParticipants (Cohort 2) will receive Ipatasertib orally daily on Days 1-28 of Cycle 1 (35-day cycle) and on Days 1-21 of subsequent cycles (28-day cycles). Atezolizumab will be administered by IV infusion on Days 8 and 22 of Cycle 1 and on Days 1 and 15 of subsequent cycles. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl
EXPERIMENTALSafety Run-In (Cohort 3): Participants will receive in Cycles 1 and 2 (28 day cycles), Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15 and AC (Doxorubicin and Cyclophosphamide) via IV infusion on Days 1 and 15. In Cycles 3-5, participants will receive Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15, with Paclitaxel administered by IV infusion on Days 1, 8, 15 and 22. All participants in this cohort will continue to be treated for five cycles (28-day cycles; 20 weeks) or until disease progression or unacceptable toxicity, whichever occurs first.
Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl
EXPERIMENTALExpansion (Cohort 3): Participants will receive in Cycles 1 and 2 (28 day cycles), Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15 and AC (Doxorubicin and Cyclophosphamide) via IV infusion on Days 1 and 15. In Cycles 3-5, participants will receive Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15, with Paclitaxel administered by IV infusion on Days 1, 8, 15 and 22. All participants in this cohort will continue to be treated for five cycles (28-day cycles; 20 weeks) or until disease progression or unacceptable toxicity, whichever occurs first.
Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl
EXPERIMENTALSafety Run-In (Cohort 3): Participants will receive in Cycles 1 and 2 (28 day cycles), Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15 and AC (Doxorubicin and Cyclophosphamide) via IV infusion on Days 1 and 15. In Cycles 3-5, participants will receive Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15, with Paclitaxel administered by IV infusion on Days 1, 8, 15 and 22. All participants in this cohort will continue to be treated for five cycles (28-day cycles; 20 weeks) or until disease progression or unacceptable toxicity, whichever occurs first.
Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl
EXPERIMENTALExpansion (Cohort 3): Participants will receive in Cycles 1 and 2 (28 day cycles), Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15 and AC (Doxorubicin and Cyclophosphamide) via IV infusion on Days 1 and 15. In Cycles 3-5, participants will receive Ipatasertib orally daily on Days 1-21, Atezolizumab via IV infusion on Days 1 and 15, with Paclitaxel administered by IV infusion on Days 1, 8, 15 and 22. All participants in this cohort will continue to be treated for five cycles (28-day cycles; 20 weeks) or until disease progression or unacceptable toxicity, whichever occurs first.
Arm H: Ipat + Atezo + Pacl
EXPERIMENTALParticipants (Cohort 4) will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by intravenous (IV) infusion on Days 1 and 15 of each 28 day cycle. Paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All participants in this cohort will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
Interventions
Ipatasertib will be administered at a dose of 400 milligrams (mg) orally daily on Days 1-21 of each 28 day cycle for all arms except for arms F1/F2 where it will be administered at a dose of 300 milligrams (mg) orally daily for the first two cycles and 400 mg for the remaining three cycles.
Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m\^2) as IV infusion on Days 1, 8, and 15 of each 28 day cycle for all arms, with the exceptions of Arms F1, F2, G1 and G2, where it will be also administered on Day 22 as well, of each 28 day cycle.
Atezolizumab will be administered by IV infusion at a fixed dose of 840 mg on Days 1 and 15 of each 28 day cycle for all arms, although in Arms C1/C2, it will be administered on Day 15 of Cycle 1 followed by Days 1 and 15 in subsequent cycles.
Nab-paclitaxel will be administered by IV infusion at a dose of 100 mg/m\^2 on Days 1, 8, and 15 of each 28 day cycle.
AC (Doxorubicin and Cyclophosphamide) will be administered by IV infusion at 60 mg/m\^2 and 600 mg/m\^2 respectively on Days 1 and 15 of Cycles 1 and 2 for Arms F1, F2, G1 and G2.
Eligibility Criteria
You may qualify if:
- General:
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Adequate hematologic and organ function.
- For Cohorts 1, 2 and 4: Life expectancy of at least 6 months.
- For men and women of child bearing potential: agreement to remain abstinent or use protocol defined contraceptive measures during the treatment period and for at least 28 days after the last dose of ipatasertib, 6 months after the last dose of paclitaxel, nab-paclitaxel, or doxorubicin, and 12 months after the last dose of cyclophosphamide, and 5 months after the last dose of atezolizumab, whichever occurs later along with refraining from donating sperm or eggs during this same period.
- Disease-specific:
- For Cohorts 1, 2 and 4: histologically documented TNBC that is locally advanced or metastatic and is not amenable to resection with curative intent.
- For Cohort 2: disease progression following one or two lines of systemic therapy for inoperable locally advanced or metastatic TNBC.
- For Cohorts 1, 2 and 4: measurable disease according to RECIST v1.1 criteria.
- For Cohort 2: Treated brain or spinal cord metastases are allowed if participants have stable disease and are not on steroid treatment.
- For Cohort 3: histologically documented TNBC with a primary breast tumour size of \> 2 cm by at least one radiographic or clinical measurement and disease stage at presentation of cT2-4 cN0-3 cM0.
- For Cohort 3: participant agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment.
- For Cohort 4: participants must have centrally confirmed PD-L1-positive tumour.
You may not qualify if:
- General:
- History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
- Active infection requiring antibiotics.
- History of or current evidence of HIV infection.
- Known clinically significant history of liver disease.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure (other than anticipated breast surgery for Cohort 3) during the course of the study.
- Pregnant or breastfeeding.
- New York Heart Association (NYHA) Class II, III, or IV heart failure; left ventricular ejection fraction \< 50%; or active ventricular arrhythmia requiring medication.
- Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1.
- Prior treatment with an Akt inhibitor.
- Disease-specific:
- For Cohorts 1 and 4: history of or known presence of brain or spinal cord metastases.
- For Cohorts 1 and 4: participants who have received previous systemic therapy for inoperable locally advanced or metastatic TNBC, including chemotherapy, immune checkpoint inhibitors, or targeted agents.
- Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
- Participants who have received palliative radiation treatment to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 and have recovered from all acute, reversible effects.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Pacific Shores Medical Group
Long Beach, California, 90813, United States
St Vincents Hospital; Cardiopulmonary transplant Ambulatory Care Dept
Darlinghurst, New South Wales, 2010, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Peter MacCallum Cancer Center
North Melbourne, Victoria, 3051, Australia
Institut de Cancerologie de l Ouest
Angers, 49055, France
Institut Bergonie
Bordeaux, 33076, France
Centre Georges Francois Leclerc
Dijon, 21000, France
Institut Curie
Paris, 75005, France
Gustave Roussy
Villejuif, 94805, France
Hospital de la Santa Creu i Sant Pau
Barcelona, 8041, Spain
Hospital Universitario La Paz
Madrid, 280146, Spain
Hospital Clinico San Carlos; Servicio de Oncologia
Madrid, 28040, Spain
Hospital Universitario Fundacion Jimenez Diaz.
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Madrid, 28050, Spain
Hospital Universitario Virgen del Rocío
Seville, 41013, Spain
Barts Cancer Institute
London, E1 2AT, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH, United Kingdom
Related Publications (1)
Schmid P, Turner NC, Barrios CH, Isakoff SJ, Kim SB, Sablin MP, Saji S, Savas P, Vidal GA, Oliveira M, O'Shaughnessy J, Italiano A, Espinosa E, Boni V, White S, Rojas B, Freitas-Junior R, Chae Y, Bondarenko I, Lee J, Torres Mattos C, Martinez Rodriguez JL, Lam LH, Jones S, Reilly SJ, Huang X, Shah K, Dent R. First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results. Clin Cancer Res. 2024 Feb 16;30(4):767-778. doi: 10.1158/1078-0432.CCR-23-2084.
PMID: 38060199DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 7, 2019
First Posted
January 11, 2019
Study Start
February 13, 2018
Primary Completion
March 16, 2022
Study Completion
March 16, 2022
Last Updated
October 30, 2024
Results First Posted
October 30, 2024
Record last verified: 2024-08