Breast CancerPhase 1NCT03800836
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 1 study testing Ipatasertib, Paclitaxel and Atezolizumab in people with Breast Cancer, run by Hoffmann-La Roche at 18 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Ipatasertib, Paclitaxel and Atezolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 18 sitesin 5 countries
- Study dates
- 13 Feb 2018to 16 Mar 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
- Uncontrolled pleural effusion, pericardial effusion, or ascites.
- Uncontrolled tumor related complications.
- Uncontrolled hypercalcaemia or symptomatic hypercalcaemia requiring continued use of bisphosphonate therapy.
- Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1.
- For Cohort 3, participants with the following are excluded: [1] prior history of invasive breast cancer; [2] prior systemic therapy for treatment and/or prevention of invasive breast cancer; [3] previous therapy with anthracyclines or taxanes for any malignancy; [4] bilateral breast cancer; [5] undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes; [6] undergone axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy; [6] history of other malignancy within 5 years prior to screening; [7] history of cerebrovascular accident within 12 months prior to initiation of study treatment; [8] cardiopulmonary dysfunction; [9] known allergy or hypersensitivity to the components of cyclophosphamide/doxorubicin formulations and filgrastim or pegfilgrastim formulations; [10] severe infection within 4 weeks prior to initiation of study treatment; [11] treatment with therapeutic oral or IV (Intravenous) antibiotics within 2 weeks prior to initiation of study treatment and [12] prior treatment with CD137 agonists or immune checkpoint - blockade therapies.
- Ipatasertib-specific:
- History of Type I or Type II diabetes mellitus requiring insulin.
- Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
- History of or active inflammatory bowel disease or active bowel inflammation.
- Clinically significant lung disease.
- Treatment with strong CYP3A inhibitors or strong CYP3A inducers.
- Atezolizumab-specific:
- Active or history of autoimmune disease or immune deficiency.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- Prior allogeneic stem cell or solid organ transplantation.
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with atezolizumab or within 5 months after the last dose of atezolizumab.
- History of hypersensitivity reactions to study drug or any component of the study drug formulation.
- Treatment with systemic immunostimulatory agents and immunosuppressive medication treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.
- Paclitaxel-specific:
- Grade >= 2 peripheral neuropathy.
Trial locations and contacts
18 sites in 5 countries.
18 sites in 5 countries
Spain7 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, 8041
Hospital Universitario La Paz
Madrid, 280146
Hospital Clinico San Carlos; Servicio de Oncologia
Madrid, 28040
Hospital Universitario Fundacion Jimenez Diaz.
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Madrid, 28050
Hospital Universitario Virgen del Rocío
Seville, 41013
France5 sites
Institut de Cancerologie de l Ouest
Angers, 49055
Institut Bergonie
Bordeaux, 33076
Centre Georges Francois Leclerc
Dijon, 21000
Institut Curie
Paris, 75005
Gustave Roussy
Villejuif, 94805
Australia3 sites
St Vincents Hospital; Cardiopulmonary transplant Ambulatory Care Dept
Darlinghurst, New South Wales, 2010
Austin Hospital
Heidelberg, Victoria, 3084
Peter MacCallum Cancer Center
North Melbourne, Victoria, 3051
United Kingdom2 sites
Barts Cancer Institute
London, E1 2AT
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH
United States1 site
Pacific Shores Medical Group
Long Beach, California, 90813
About this study
Official title: 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
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.
- Conditions
- Breast Cancer
- Being tested
- Ipatasertib, Paclitaxel, Atezolizumab, Nab-Paclitaxel, AC
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpatasertibDrug
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.
PaclitaxelDrug
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.
AtezolizumabDrug
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-PaclitaxelDrug
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.
ACDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A1: Ipat + Atezo + Pacl | Experimental | Safety 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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm A2: Ipat + Atezo + Pacl | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm A3: Ipat + Atezo + Pacl | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm B1: Ipat + Atezo + Nab-Pacl | Experimental | Safety 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. Receives: Drug: Ipatasertib; Drug: Atezolizumab; Drug: Nab-Paclitaxel |
| Arm B2: Ipat + Atezo + Nab-Pacl | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Atezolizumab; Drug: Nab-Paclitaxel |
| Arm C1: (Ipat + Pacl) (2 weeks) + Atezo | Experimental | Safety 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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm C2 (Ipat + Pacl) (2 weeks) + Atezo | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm D1: (Atezo + Pacl) (2 weeks) + Ipat | Experimental | Safety 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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm D2: (Atezo + Pacl) (2 weeks) + Ipat | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
| Arm E: Ipat + Atezo | Experimental | Participants (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. Receives: Drug: Ipatasertib; Drug: Atezolizumab |
| Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl | Experimental | Safety 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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab; Drug: AC |
| Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab; Drug: AC |
| Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl | Experimental | Safety 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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab; Drug: AC |
| Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl | Experimental | Expansion (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab; Drug: AC |
| Arm H: Ipat + Atezo + Pacl | Experimental | Participants (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. Receives: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
DOR was defined as the time from the first occurrence of a documented confirmed CR or PR to the first date of recorded disease progression (PD), as determined by the investigator according to RECIST v1.1 or death from any cause. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduced 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 diameter of target lesions, taking as reference the smallest sum on study (nadir) including baseline; the appearance of one or more new lesions. No participants were enrolled in cohort 4, and hence no data was reported. Participants who did not progress or died at time of analysis were censored at last disease assessment date.
Measured: 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
PFS: time from enrollment to date of 1st recorded occurrence of PD, as determined by investigator according to RECIST v1.1 or death from any cause, whichever occurs first. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (nadir) including baseline; appearance of one or more new lesions. Data for participants who did not experience PD or death was censored at last date of evaluable tumor assessment. No participants were enrolled in cohort 4, and hence no data was reported.
Measured: 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)
OS was defined as the time from enrollment to death from any cause.
Measured: From enrollment up to death due to any cause (up to approximately 43.6 months).
Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib
Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
Measured: 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)
Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
Measured: 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)
Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment
Participants were considered to be ADA positive if they were ADA negative or were missing data at Baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at Baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the Baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline and all postbaseline samples were negative, or if they were ADA positive at Baseline but did not have any postbaseline samples with a titer that was at least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected). Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
Measured: From baseline up to 30 days from the last dose of atezolizumab (to approximately 4 years 1.1 month)
Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab
Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
Measured: Cycle 1 Day 1 and 15: predose and 30 mins post dose; Cycle 2: Day 1 and 15 predose, Cycle 3, 4, 8, 12, and 16 Day 1: predose; treatment discontinuation visit
Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1
CBR was defined as percentage of participants with stable disease (SD) for at least 24 weeks or with confirmed CR or PR as determined by the investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have 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. Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
Measured: From screening up to confirmed SD or CR or PR (up to approximately 43.6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start13 Feb 2018
- Primary completion16 Mar 2022
- Study completion16 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03800836
- Sponsor's protocol ID
- CO40151
- Other IDs
- 2017-001957-15, 2017
- Status last verified
- Aug 2024
- First submitted
- 7 Jan 2019
- Last updated
- 30 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38060199
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03800836
- Acronym / sponsor ID
- CO40151
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 13 Feb 2018 (actual)
- Primary completion
- 16 Mar 2022 (actual)
- Study completion
- 16 Mar 2022 (actual)
- First posted
- 11 Jan 2019 (actual)
- Results
- Posted 30 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Arm A1: Ipat + Atezo + Pacl | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabSafety 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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabExpansion (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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabExpansion (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 | Experimental | Drug: Ipatasertib, Drug: Atezolizumab, Drug: Nab-PaclitaxelSafety 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 | Experimental | Drug: Ipatasertib, Drug: Atezolizumab, Drug: Nab-PaclitaxelExpansion (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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabSafety 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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabExpansion (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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabSafety 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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabExpansion (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 | Experimental | Drug: Ipatasertib, Drug: AtezolizumabParticipants (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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: Atezolizumab, Drug: ACSafety 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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: Atezolizumab, Drug: ACExpansion (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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: Atezolizumab, Drug: ACSafety 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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: Atezolizumab, Drug: ACExpansion (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 | Experimental | Drug: Ipatasertib, Drug: Paclitaxel, Drug: AtezolizumabParticipants (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- For Cohorts 1, 2 and 4: histologically documented TNBC that is locally advanced or metastatic and is not amenable to resection with curative intent.
Key exclusion criteria (35 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpatasertibIpatasertib 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. | Drug | Arm A1: Ipat + Atezo + Pacl, Arm A2: Ipat + Atezo + Pacl, Arm A3: Ipat + Atezo + Pacl, Arm B1: Ipat + Atezo + Nab-Pacl, Arm B2: Ipat + Atezo + Nab-Pacl, Arm C1: (Ipat + Pacl) (2 weeks) + Atezo, Arm C2 (Ipat + Pacl) (2 weeks) + Atezo, Arm D1: (Atezo + Pacl) (2 weeks) + Ipat, Arm D2: (Atezo + Pacl) (2 weeks) + Ipat, Arm E: Ipat + Atezo, Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm H: Ipat + Atezo + Pacl |
| PaclitaxelPaclitaxel 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. | Drug | Arm A1: Ipat + Atezo + Pacl, Arm A2: Ipat + Atezo + Pacl, Arm A3: Ipat + Atezo + Pacl, Arm C1: (Ipat + Pacl) (2 weeks) + Atezo, Arm C2 (Ipat + Pacl) (2 weeks) + Atezo, Arm D1: (Atezo + Pacl) (2 weeks) + Ipat, Arm D2: (Atezo + Pacl) (2 weeks) + Ipat, Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm H: Ipat + Atezo + Pacl |
| AtezolizumabAtezolizumab 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. | Drug | Arm A1: Ipat + Atezo + Pacl, Arm A2: Ipat + Atezo + Pacl, Arm A3: Ipat + Atezo + Pacl, Arm B1: Ipat + Atezo + Nab-Pacl, Arm B2: Ipat + Atezo + Nab-Pacl, Arm C1: (Ipat + Pacl) (2 weeks) + Atezo, Arm C2 (Ipat + Pacl) (2 weeks) + Atezo, Arm D1: (Atezo + Pacl) (2 weeks) + Ipat, Arm D2: (Atezo + Pacl) (2 weeks) + Ipat, Arm E: Ipat + Atezo, Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm H: Ipat + Atezo + Pacl |
| Nab-PaclitaxelNab-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. | Drug | Arm B1: Ipat + Atezo + Nab-Pacl, Arm B2: Ipat + Atezo + Nab-Pacl |
| ACAC (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. | Drug | Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl, Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl |
Primary outcome
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
Time frame: From screening up to approximately 43.6 months
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.
Cohort 3: Pathological Complete Response (pCR) Rate
Time frame: 2-6 weeks following last dose of study treatment (up to 69 weeks)
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.
Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs)
Time frame: 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)
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.
8 secondary outcomes
Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1
Time frame: 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
Time frame: 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)
Time frame: From enrollment up to death due to any cause (up to approximately 43.6 months).
Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib
Time frame: 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)
Time frame: 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)
Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment
Time frame: From baseline up to 30 days from the last dose of atezolizumab (to approximately 4 years 1.1 month)
Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab
Time frame: Cycle 1 Day 1 and 15: predose and 30 mins post dose; Cycle 2: Day 1 and 15 predose, Cycle 3, 4, 8, 12, and 16 Day 1: predose; treatment discontinuation visit
Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1
Time frame: From screening up to confirmed SD or CR or PR (up to approximately 43.6 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38060199Schmid 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
18 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipatasertib, Paclitaxel and Atezolizumab in people with Breast Cancer, run by Hoffmann-La Roche at 18 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Spain, France, Australia, United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: From screening up to approximately 43.6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03800836, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2024.