CompletedNCT03800836Updated Oct 30, 2024Results posted

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 interventional study of Ipatasertib and Paclitaxel in Breast Cancer, sponsored by Hoffmann-La Roche. Completed at 18 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-30.

Sponsored by Hoffmann-La Roche · Phase 1, Interventional, and Treatment

From the registry’s dates

Registered 10 months after the study started (first participant enrolled Feb 2018, registered Jan 2019).

Phase: Phase 1
Study type: Interventional
Enrollment: 139
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

Breast Cancer

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In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 139 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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.
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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 139 participants (actual)

Study arms

Experimental
Arm A1: Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm A2: Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm A3: Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm B1: Ipat + Atezo + Nab-Pacl
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.
Drug: Ipatasertib · Drug: Atezolizumab · Drug: Nab-Paclitaxel
Experimental
Arm B2: Ipat + Atezo + Nab-Pacl
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.
Drug: Ipatasertib · Drug: Atezolizumab · Drug: Nab-Paclitaxel
Experimental
Arm C1: (Ipat + Pacl) (2 weeks) + Atezo
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm C2 (Ipat + Pacl) (2 weeks) + Atezo
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm D1: (Atezo + Pacl) (2 weeks) + Ipat
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm D2: (Atezo + Pacl) (2 weeks) + Ipat
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab
Experimental
Arm E: Ipat + Atezo
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.
Drug: Ipatasertib · Drug: Atezolizumab
Experimental
Arm F1: Ipat + Atezol + AC / Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab · Drug: AC
Experimental
Arm F2: Ipat + Atezol + AC / Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab · Drug: AC
Experimental
Arm G1: Ipat + Atezol + AC / Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab · Drug: AC
Experimental
Arm G2: Ipat + Atezol + AC / Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab · Drug: AC
Experimental
Arm H: Ipat + Atezo + Pacl
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.
Drug: Ipatasertib · Drug: Paclitaxel · Drug: Atezolizumab

Interventions

DrugIpatasertib
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.
DrugPaclitaxel
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.
DrugAtezolizumab
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.
DrugNab-Paclitaxel
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.
DrugAC
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.

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
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)

Secondary outcomes

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.
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
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.
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)
OS was defined as the time from enrollment to death from any cause.
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
Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
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)
Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
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
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.
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
Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.
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
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.
Time frame: From screening up to confirmed SD or CR or PR (up to approximately 43.6 months)

Results

Posted Oct 30, 2024

Participant flow

Participants took part in this study from 13 February 2018 to 16 March 2022.

Participant flow — Overall Study
Milestone	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D	Cohort 2-Arm E	Cohort 3-Arm F
Started	71	20	13	12	17	6
Safety population	70	20	12	12	17	6
Completed	0	0	0	0	0	0
Not completed	71	20	13	12	17	6
Withdrew: Other	2	1	0	2	0	1
Withdrew: Lost to follow-up	2	0	1	1	3	0
Withdrew: Withdrawal by subject	1	0	0	0	0	0
Withdrew: Physician decision	31	3	6	4	4	5
Withdrew: Death	34	16	5	5	10	0
Withdrew: Symptomatic deterioration	1	0	1	0	0	0

Outcome measures

PrimaryCohort 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.

Time frame:: From screening up to approximately 43.6 months
Reported as:: Number · percentage of participants

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
percentage of participants	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D
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	51.4 (39.17 to 63.56)	65.0 (40.78 to 84.61)	66.7 (34.89 to 90.08)	33.3 (9.92 to 65.11)

SecondaryCohort 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.

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)
Reported as:: Median · months

Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1
months	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D
Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1	7.8 (5.6 to 12.9)	7.3 (5.0 to 9.2)	9.2 (3.9 to 14.7)	4.8 (3.7 to NA)

PrimaryCohort 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.

Time frame:: 2-6 weeks following last dose of study treatment (up to 69 weeks)
Reported as:: Number · percentage of participants

Cohort 3: Pathological Complete Response (pCR) Rate
percentage of participants	Cohort 3-Arm F
Cohort 3: Pathological Complete Response (pCR) Rate	50

PrimaryCohort 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.

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)
Reported as:: Count of participants · Participants

Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs)
Participants	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D	Cohort 2-Arm E	Cohort 3-Arm F
Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs)	70	20	12	12	17	6

SecondaryCohort 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.

Time frame:: From enrollment up to disease progression or death due to any cause whichever occurs first (up to approximately 43.6 months)
Reported as:: Median · months

Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1
months	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D
Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1	7.2 (5.3 to 7.4)	6.6 (3.4 to 9.2)	8.8 (5.6 to 12.9)	6.5 (5.2 to 11.3)

SecondaryCohort 1 and Cohort 4: Overall Survival (OS)

OS was defined as the time from enrollment to death from any cause.

Time frame:: From enrollment up to death due to any cause (up to approximately 43.6 months).
Reported as:: Median · months

Cohort 1 and Cohort 4: Overall Survival (OS)
months	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D
Cohort 1 and Cohort 4: Overall Survival (OS)	28.3 (17.2 to 43.0)	20.1 (11.1 to 30.8)	NA (21.2 to NA)	NA (11.7 to NA)

SecondaryCohort 1 and Cohort 4: Plasma Concentration of Ipatasertib

Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.

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)
Reported as:: Geometric mean · nanograms per milliliter (ng/mL)

Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib
nanograms per milliliter (ng/mL)	Cohort 1- Arm A1	Cohort 1- A2	Cohort1- Arm A3	Cohort 1- Arm B1	Cohort 1- Arm B2	Cohort 1- Arm C1	Cohort 1- Arm C2	Cohort 1- Arm D1	Cohort 1- Arm D2
Cycle 1 Day 15 Pre-dose	47.9 ± 47.2	13.6 ± 783.4	29.4 ± 163.1	30.2 ± 37.1	46.9 ± 172.8	61.1 ± 94.3	77.3 ± 207.0	—	—
Cycle 1 Day 15 1 hour Post-dose	507 ± 43.6	182 ± 167.0	258 ± 127.2	253 ± 128.0	219 ± 186.6	—	—	—	—
Cycle 1 Day 15 2 hour Post-dose	318 ± 21.4	318 ± 47.8	421 ± 51.5	287 ± 35.7	282 ± 235.6	—	—	225 ± 41.9	190 ± 484.7
Cycle 1 Day 15 4 hour Post-dose	226 ± 32.7	255 ± 39.7	305 ± 40.8	225 ± 10.0	266 ± 78.1	—	—	—	—
Cycle 1 Day 15 6 hour Post-dose	—	182 ± 39.2	233 ± 46.7	165 ± 25.0	186 ± 80.3	—	—	—	—
Cycle 2 Day 15 Pre-dose	—	—	—	—	—	44.9 ± 43.3	50.3 ± 31.4	29.2 ± 59.5	31.6 ± 53.1
Cycle 2 Day 15 1 hour Post-dose	—	—	—	—	—	260 ± 21.6	614 ± 34.2	232 ± 150.0	364 ± 81.4
Cycle 2 Day 15 2 hour Post-dose	—	—	—	—	—	575 ± 22.5	500 ± 18.3	311 ± 67.5	610 ± 36.7
Cycle 2 Day 15 4 hour Post-dose	—	—	—	—	—	402 ± 44.9	340 ± 29.9	258 ± 20.6	433 ± 41.7
Cycle 2 Day 15 6 hour Post-dose	—	—	—	—	—	253 ± 31.7	273 ± 15.3	162 ± 8.2	234 ± 32.6
Cycle 3 Day 15 1 to 3 hour Post-dose	—	126 ± 241.7	196 ± 133.7	134 ± 82.8	214 ± 130.8	127 ± 369.0	155 ± 282.3	233 ± 120.9	382 ± 87.9

SecondaryCohort 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.

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)
Reported as:: Geometric mean · ng/mL

Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720)
ng/mL	Cohort 1- Arm A1	Cohort 1-Arm A2	Cohort 1-Arm A3	Cohort 1- Arm B1	Cohort 1- Arm B2	Cohort 1- Arm C1	Cohort 1- Arm C2	Cohort 1- Arm D1	Cohort 1- Arm D2
Cycle 1 Day 15 Pre-dose	27.0 ± 32.4	8.27 ± 404.3	15.0 ± 165.9	23.3 ± 58.3	24.1 ± 97.7	30.9 ± 48.3	36.4 ± 356.1	—	—
Cycle 1 Day 15 1 hour Post-dose	200 ± 58.3	61.8 ± 209.2	85.9 ± 119.9	126 ± 158.4	86.4 ± 135.3	—	—	—	—
Cycle 1 Day 15 2 hour Post-dose	151 ± 29.9	124 ± 55.0	153 ± 68.8	166 ± 102.2	120 ± 193.0	—	—	78.1 ± 125.6	177 ± 37.1
Cycle 1 Day 15 4 hour Post-dose	118 ± 26.1	121 ± 41.5	157 ± 62.9	154 ± 39.8	134 ± 99.2	—	—	—	—
Cycle 1 Day 15 6 hour Post-dose	—	106 ± 47.3	133 ± 60.3	120 ± 45.6	101 ± 82.8	—	—	—	—
Cycle 2 Day 15 Pre-dose	—	—	—	—	—	22.5 ± 27.6	20.5 ± 38.4	15.2 ± 81.4	24.4 ± 76.7
Cycle 2 Day 15 1 hour Post-dose	—	—	—	—	—	41.3 ± 90.1	148 ± 39.4	70.5 ± 244.4	140 ± 94.2
Cycle 2 Day 15 2 hour Post-dose	—	—	—	—	—	206 ± 35.1	184 ± 28.0	120 ± 171.0	355 ± 22.9
Cycle 2 Day 15 4 hour Post-dose	—	—	—	—	—	185 ± 30.2	146 ± 46.5	131 ± 30.8	402 ± 43.4
Cycle 2 Day 15 6 hour Post-dose	—	—	—	—	—	124 ± 11.4	137 ± 30.4	98.8 ± 77.3	232 ± 57.4
Cycle 3 Day 15 1 to 3 hour Posst-dose	—	47.1 ± 238.3	69.4 ± 161.2	68.6 ± 131.8	79.4 ± 150.8	50.4 ± 299.8	45.0 ± 182.3	84.6 ± 227.5	144 ± 121.6

SecondaryCohort 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.

Time frame:: From baseline up to 30 days from the last dose of atezolizumab (to approximately 4 years 1.1 month)
Reported as:: Count of participants · Participants

Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment
Participants	Cohort 1-Arm A1	Cohort 1- Arm A2	Cohort 1- Arm A3	Cohort 1-Arm B1	Cohort 1- Arm B2	Cohort 1-Arm C1	Cohort 1- Arm C2	Cohort 1- Arm D1	Cohort 1- Arm D2
Baseline: Positive for ADA	0	0	0	0	0	0	0	0	0
Baseline: Negative for ADA	6	13	43	6	14	0	0	6	6
Post Baseline: Positive for Treatment Emergent ADA	0	3	2	0	3	2	1	0	0
Post Baseline: Negative for Treatment Emergent ADA	6	10	38	6	9	4	5	6	6

SecondaryCohort 1 and Cohort 4: Plasma Concentration of Atezolizumab

Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1.

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
Reported as:: Geometric mean · ng/mL

Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab
ng/mL	Cohort 1- Arm A1	Cohort 1-Arm A2	Cohort 1-Arm A3	Cohort 1- Arm B1	Cohort 1- Arm B2	Cohort 1-Arm C1	Cohort 1-Arm C2	Cohort 1- Arm D1	Cohort 1- Arm D2
Cycle 1 Day 1 Pre-dose	—	—	853 ± 1344.8	—	65.3 ± 3.4	—	—	82.5 ± 7.6	—
Cycle 1 Day 1 30 min Post-dose	354000 ± 12.2	330000 ± 18.1	329000 ± 25.3	315000 ± 5.4	365000 ± 19.2	—	—	335000 ± 13.9	339000 ± 13.6
Cycle 1 Day 15 Pre-Dose	106000 ± 12.1	75200 ± 170.2	94500 ± 27.8	93100 ± 15.6	91700 ± 21	126 ± NA	—	87100 ± 31.6	108000 ± 32.2
Cycle 1 Day 15 30 min Post-dose	—	—	351000 ± 49	—	393000 ± NA	362000 ± 8.8	370000 ± 9.8	274000 ± NA	345000 ± NA
Cycle 2 Day 1 Pre-Dose	143000 ± 34.3	90200 ± 883.4	149000 ± 45	99700 ± 118.4	132000 ± 45	101000 ± 39.1	121000 ± 21.6	147000 ± 35.3	156000 ± 20
Cycle 2 Day 15 Pre-Dose	—	—	120000 ± NA	—	180000 ± NA	124000 ± 83.8	189000 ± 18.2	178000 ± 41.7	194000 ± 26.1
Cycle 3 Day 1 Pre-Dose	193000 ± 85.5	105000 ± 1195.9	216000 ± 50.7	219000 ± 32	246000 ± 33	166000 ± 34.7	230000 ± 16.1	197000 ± 32.4	247000 ± 9.7
Cycle 4 Day 1 Pre-Dose	347000 ± 12.4	179000 ± 256.2	283000 ± 23.8	239000 ± 37	283000 ± 16.7	293000 ± 40.3	293000 ± 18.3	250000 ± 43.9	247000 ± 46
Cycle 8 Day 1 Pre-Dose	376000 ± 11.9	398000 ± 34.4	345000 ± 55.9	385000 ± 19.2	293000 ± 7.1	386000 ± 32.5	545000 ± 29.6	153000 ± 119.9	357000 ± 10.3
Cycle 12 Day 1 Pre-Dose	333000 ± NA	505000 ± 14.4	—	—	285000 ± NA	122000 ± NA	384000 ± 11.8	393000 ± 26	—
Cycle 16 Day 1Pre-Dose	562000 ± 40.3	408000 ± 42	—	388000 ± NA	—	135000 ± NA	—	—	—
Treatment Discontinuation	—	97400 ± 153.2	135000 ± 99.8	253000 ± 81.9	195000 ± 47.5	337000 ± 31.7	181000 ± 40.9	274000 ± 113	178000 ± 67.9

SecondaryCohort 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.

Time frame:: From screening up to confirmed SD or CR or PR (up to approximately 43.6 months)
Reported as:: Number · percentage of participants

Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1
percentage of participants	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D
Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1	58.6 (46.17 to 70.23)	65.0 (40.78 to 84.61)	75.0 (42.81 to 94.51)	58.3 (27.67 to 84.83)

Adverse events

Collected over 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). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1- Arm A	34/70 (48.6%)	26/70 (37.1%)	70/70 (100%)
Cohort 1- Arm B	16/20 (80%)	9/20 (45%)	20/20 (100%)
Cohort 1- Arm C	5/12 (41.7%)	5/12 (41.7%)	12/12 (100%)
Cohort 1- Arm D	5/12 (41.7%)	4/12 (33.3%)	12/12 (100%)
Cohort 2- Arm E	10/17 (58.8%)	5/17 (29.4%)	17/17 (100%)
Cohort 3- Arm F	0/6 (0%)	4/6 (66.7%)	6/6 (100%)

Most frequent serious events

Showing 10 of 51

Most frequent serious events
Event	Cohort 1- Arm A	Cohort 1- Arm B	Cohort 1- Arm C	Cohort 1- Arm D	Cohort 2- Arm E	Cohort 3- Arm F
NeutropeniaBlood and lymphatic system disorders	1/70	1/20	0/12	0/12	0/17	2/6
Postoperative wound infectionInfections and infestations	0/70	0/20	0/12	0/12	0/17	1/6
PyelonephritisInfections and infestations	0/70	0/20	0/12	0/12	0/17	1/6
HyperglycaemiaMetabolism and nutrition disorders	0/70	0/20	0/12	0/12	0/17	1/6
RashSkin and subcutaneous tissue disorders	3/70	2/20	2/12	0/12	0/17	0/6
PyrexiaGeneral disorders	1/70	2/20	1/12	0/12	1/17	0/6
ColitisGastrointestinal disorders	0/70	0/20	0/12	1/12	0/17	0/6
DiarrhoeaGastrointestinal disorders	2/70	0/20	0/12	1/12	1/17	0/6
Chest painGeneral disorders	0/70	0/20	1/12	0/12	0/17	0/6
Anal abscessInfections and infestations	0/70	0/20	1/12	0/12	0/17	0/6

Most frequent other events

Showing 10 of 230

Most frequent other events
Event	Cohort 1- Arm A	Cohort 1- Arm B	Cohort 1- Arm C	Cohort 1- Arm D	Cohort 2- Arm E	Cohort 3- Arm F
DiarrhoeaGastrointestinal disorders	59/70	15/20	10/12	9/12	9/17	6/6
NauseaGastrointestinal disorders	37/70	16/20	4/12	5/12	5/17	5/6
AnaemiaBlood and lymphatic system disorders	17/70	6/20	3/12	2/12	1/17	4/6
AlopeciaSkin and subcutaneous tissue disorders	26/70	11/20	6/12	7/12	0/17	4/6
Neuropathy peripheralNervous system disorders	20/70	9/20	7/12	0/12	1/17	0/6
VomitingGastrointestinal disorders	15/70	11/20	4/12	3/12	3/17	1/6
AstheniaGeneral disorders	19/70	7/20	3/12	4/12	9/17	3/6
Nail dystrophySkin and subcutaneous tissue disorders	2/70	0/20	0/12	0/12	0/17	3/6
RashSkin and subcutaneous tissue disorders	25/70	8/20	3/12	4/12	7/17	3/6
FatigueGeneral disorders	32/70	6/20	5/12	4/12	2/17	2/6

Baseline characteristics

Safety population included all participants who received any study treatment.

Age, Continuous
Age, Continuous(years)	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D	Cohort 2-Arm E	Cohort 3-Arm F	Total
Mean	56.6 ± 13.0	50.2 ± 9.6	46.4 ± 14.0	48.8 ± 9.6	52.1 ± 11.2	53.2 ± 7.4	53.4 ± 12.3

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D	Cohort 2-Arm E	Cohort 3-Arm F	Total
Female	70	20	12	12	17	6	137
Male	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D	Cohort 2-Arm E	Cohort 3-Arm F	Total
American Indian or Alaska Native	1	0	0	0	0	0	1
Asian	5	0	0	1	0	0	6
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	1	0	0	0	0	0	1
White	55	15	11	9	17	6	113
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	8	5	1	2	0	0	16

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Cohort 1-Arm A	Cohort 1-Arm B	Cohort 1-Arm C	Cohort 1-Arm D	Cohort 2-Arm E	Cohort 3-Arm F	Total
Hispanic or Latino	7	3	1	0	5	2	18
Not Hispanic or Latino	51	14	9	11	11	4	100
Not Stated	7	2	2	0	1	0	12
Unknown	5	1	0	1	0	0	7

Study locations

18 sites

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
Sevilla, 41013, Spain
Barts Cancer Institute
London, E1 2AT, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH, United Kingdom

References and documents

Study documents

Protocol and statistical analysis plan · Jan 26, 2021

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Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 30, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03800836
Lead sponsor: Hoffmann-La Roche
Responsible party: Sponsor
First posted: Jan 11, 2019
Start date: Feb 13, 2018
Primary completion: Mar 16, 2022
Completion: Mar 16, 2022
Results posted: Oct 30, 2024
Last update: Oct 30, 2024

Study contacts

Clinical Trials

study director · Hoffmann-La Roche

Oversight

FDA-regulated drug: Yes
FDA-regulated device: No

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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

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