Breast Cancer
Conditions
Brief summary
This is a study consisting of four cohorts in this setting. In Cohort 1, the safety and efficacy of ipatasertib (ipat) in combination with atezolizumab (atezo) and paclitaxel (pac) or nab-paclitaxel will be evaluated for participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not previously received chemotherapy. In Cohort 2, ipatasertib and atezolizumab (with no chemotherapy), will be administered to participants with locally advanced or metastatic TNBC. In Cohort 3, the safety and efficacy of neoadjuvant ipatasertib, atezolizumab, doxorubicin and cyclophosphamide (AC) (Ipat + Atezo + AC) followed by Ipat + Atezo + Pac will be evaluated in participants with locally advanced Type 2-4 (T2-4) TNBC. In Cohort 4, the safety and efficacy of Ipat + Atezo + Pac will be evaluated in participants with PD-L1 (Programmed Death-Ligand-1) positive locally advanced or metastatic TNBC that is not amenable to resection and who have not previously received chemotherapy in the advanced setting.
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Day 15 Cycle 1: pre-dose and 1, 2, 4 and 6 hours post-dose, Day 15 Cycle2: predose and 1, 2, 4 and 6 hours post-dose and Day 15 Cycle 3 - post dose up to - 3 hours (each cycle is of 28 days) | Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1. |
| Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Day 15 Cycle 1 - pre-dose and 1 hour, 2 hours, 4 hours and 6 hours post-dose, Day 15 Cycle2: predose and 1 hour, 2 hours, 4 hours and 6 hours post-dose and Day 15 Cycle 3 - post dose up to - 3 hours (each cycle is of 28 days) | Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1. |
| Cohort 1 and Cohort 4: Overall Survival (OS) | From enrollment up to death due to any cause (up to approximately 43.6 months). | OS was defined as the time from enrollment to death from any cause. |
| Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | 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 | Since, Cohort 4 did not enroll any participants, data is only reported for Cohort 1. |
| Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1 | From screening up to confirmed SD or CR or PR (up to approximately 43.6 months) | 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. |
| Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | From baseline up to 30 days from the last dose of atezolizumab (to approximately 4 years 1.1 month) | 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. |
| Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 | From the date of first documented confirmed response (CR or PR) to disease progression or death due to any cause (up to approximately 43.6 months) | 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. |
| Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1 | From enrollment up to disease progression or death due to any cause whichever occurs first (up to approximately 43.6 months) | 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. |
Countries
Australia, France, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in this study from 13 February 2018 to 16 March 2022.
Pre-assignment details
139 participants were enrolled, 2 were not treated and excluded from analyses. 137 participants were enrolled in either Cohort 1 (Arms A \[A1,2,3\], B \[B1,2\], C \[C1,2\], and D \[D1,2\]), Cohort 2 (Arm E) or Arm F1 in Cohort 3. Sponsor made decision not to continue study enrollment before arms F2, G1, G2 (Cohort 3) and H (Cohort 4) enrolled any participants.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1-Arm A Participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who had not previously received chemotherapy in the advanced setting received 400 milligrams (mg) of ipatasertib (Ipat) orally, once daily (QD) on Days 1-21, 840 mg intravenous (IV) of atezolizumab (Atezo) on Days 1 and 15, and 80 milligrams per square meter (mg/m\^2) IV paclitaxel (Pac) on Days 1, 8, and 15 of each 28-day cycle. Following completion of a safety run-in cohort (A1), subsequent expansion arms enrolled (A2 and A3). All participants in Arm A continued to receive treatment until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or end of the study. | 70 |
| Cohort 1-Arm B Participants with locally advanced or metastatic TNBC who had not previously received chemotherapy in the advanced setting received 400 mg of Ipat orally, QD on Days 1-21, 840 mg IV of Atezo on Days 1 and 15, and 100 mg/m\^2 IV nab-paclitaxel (Nab-Pac) on Days 1, 8, and 15 of each 28-day cycle. Following completion of a safety run-in cohort (B1), a subsequent expansion arm enrolled (B2). All participants in Arm B continued to receive treatment until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or end of the study. | 20 |
| Cohort 1-Arm C Participants with locally advanced or metastatic TNBC who had not previously received chemotherapy in the advanced setting received 400 mg of Ipat orally, QD on Days 1-21, 80 mg/m2 IV Pac on Days 1, 8, and 15 and 840 mg IV Atezo on Day 15 of Cycle 1 (28 day cycle). In Cycles ≥ 2, participants received 400 mg Ipat orally on Days 1-21, 840 mg IV Atezo on Days 1 and 15 and 80 mg/m2 IV Pac on Days 1, 8, and 15 of each 28-day Cycle. Following completion of the safety run-in cohort (C1), a subsequent expansion cohort (C2) enrolled. All participants in Arm C continued to receive treatment until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or end of the study. | 12 |
| Cohort 1-Arm D Participants with locally advanced or metastatic TNBC who had not previously received chemotherapy in the advanced setting received 840 mg IV Atezo on Days 1 and 15, 80 mg/m2 IV Pac on Days 1, 8, and 15 and 400 mg Ipat orally on days 15-21 of Cycle 1 (28 day cycle). In Cycles ≥ 2, participants received 400 mg Ipat orally on Days 1-21, 80 mg/m2 IV Pac on Days 1, 8, and 15 and 840 mg IV Atezo on Days 1 and 15 of each 28 day Cycle. Following completion of the safety run-in cohort (D1), a subsequent expansion cohort (D2) enrolled. All participants in Arm D continued to receive treatment until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or end of the study. | 12 |
| Cohort 2-Arm E Participants in the second-line and third-line setting with locally advanced or metastatic TNBC received 400 mg Ipat orally QD on Days 1-28 and 840 mg IV Atezo on Days 8 and 22 of Cycle 1 (Cycle 1 = 35 days). In Cycles ≥ 2, participants received 400 mg Ipat orally on Days 1-21 and 840 mg IV Atezo on Days 1 and 15 of each cycle (Cycles ≥ 2 = 28-days) until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or end of the study. | 17 |
| Cohort 3-Arm F Participants in the safety run-in stage (arm F1) with locally advanced T2-4 TNBC received 300 mg Ipat orally QD on Days 1-21, 840mg IV Atezo on Days 1 and 15, 60 mg/m2 IV doxorubicin and 600 mg/m2 IV cyclophosphamide on Days 1 and 15 of Cycles 1 and 2 (1 Cycle=28-days). Participants then received 400 mg Ipat orally QD on Days 1-21, 840mg IV Atezo on Days 1 and 15 and 80 mg/m2 IV Pac on Days 1, 8, 15, and 22 of Cycles 3-5, until completion of 5 cycles or disease progression or unacceptable toxicity, whichever occurred first. | 6 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 34 | 16 | 5 | 5 | 10 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 1 | 3 | 0 |
| Overall Study | Other | 2 | 1 | 0 | 2 | 0 | 1 |
| Overall Study | Physician Decision | 31 | 3 | 6 | 4 | 4 | 5 |
| Overall Study | Symptomatic Deterioration | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1-Arm B | Total | Cohort 3-Arm F | Cohort 2-Arm E | Cohort 1-Arm A | Cohort 1-Arm D | Cohort 1-Arm C |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.2 years STANDARD_DEVIATION 9.6 | 53.4 years STANDARD_DEVIATION 12.3 | 53.2 years STANDARD_DEVIATION 7.4 | 52.1 years STANDARD_DEVIATION 11.2 | 56.6 years STANDARD_DEVIATION 13 | 48.8 years STANDARD_DEVIATION 9.6 | 46.4 years STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 18 Participants | 2 Participants | 5 Participants | 7 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 14 Participants | 100 Participants | 4 Participants | 11 Participants | 51 Participants | 11 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Stated | 2 Participants | 12 Participants | 0 Participants | 1 Participants | 7 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 7 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 16 Participants | 0 Participants | 0 Participants | 8 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 15 Participants | 113 Participants | 6 Participants | 17 Participants | 55 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Female | 20 Participants | 137 Participants | 6 Participants | 17 Participants | 70 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 34 / 70 | 16 / 20 | 5 / 12 | 5 / 12 | 10 / 17 | 0 / 6 |
| other Total, other adverse events | 70 / 70 | 20 / 20 | 12 / 12 | 12 / 12 | 17 / 17 | 6 / 6 |
| serious Total, serious adverse events | 26 / 70 | 9 / 20 | 5 / 12 | 4 / 12 | 5 / 17 | 4 / 6 |
Outcome results
Primary
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
Population: Efficacy evaluable population included all enrolled participants who received at least one dose of study treatment, regardless of treatment allocation. Participants without a postbaseline tumor assessment were considered as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-Arm A | 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 percentage of participants |
| Cohort 1-Arm B | 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 | 65.0 percentage of participants |
| Cohort 1-Arm C | 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 | 66.7 percentage of participants |
| 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 | 33.3 percentage of participants |
Primary
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)
Population: Safety population included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1-Arm A | Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs) | 70 Participants |
| Cohort 1-Arm B | Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs) | 20 Participants |
| Cohort 1-Arm C | Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs) | 12 Participants |
| Cohort 1-Arm D | Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs) | 12 Participants |
| Cohort 2-Arm E | Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs) | 17 Participants |
| Cohort 3-Arm F | Cohort 1, Cohort 2, Cohort 3 and Cohort 4: Number of Participants With Adverse Events (AEs) | 6 Participants |
Primary
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)
Population: Efficacy evaluable population included all enrolled participants who received at least one dose of study treatment, regardless of treatment allocation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-Arm A | Cohort 3: Pathological Complete Response (pCR) Rate | 50 percentage of participants |
Secondary
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)
Population: Efficacy evaluable population included all enrolled participants who received at least one dose of study treatment, regardless of treatment allocation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1 | 58.6 percentage of participants |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1 | 65.0 percentage of participants |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1 | 75.0 percentage of participants |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Clinical Benefit Rate (CBR) as Assessed by Investigator Based on RECIST v1.1 | 58.3 percentage of participants |
Secondary
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)
Population: Efficacy evaluable population included all enrolled participants who received at least one dose of study treatment, regardless of treatment allocation. Number analyzed are participants who had OR (i.e., a confirmed CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 | 7.8 months |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 | 7.3 months |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 | 9.2 months |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 | 4.8 months |
Secondary
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)
Population: Immunogenicity evaluable population included all participants with atleast 1 ADA assessment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at a given time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 6 Participants |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 0 Participants |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 6 Participants |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 10 Participants |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 13 Participants |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 3 Participants |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 43 Participants |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 38 Participants |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 2 Participants |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 6 Participants |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 0 Participants |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 6 Participants |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 3 Participants |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 14 Participants |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 9 Participants |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 4 Participants |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 2 Participants |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 0 Participants |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 1 Participants |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 0 Participants |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 5 Participants |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 6 Participants |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 6 Participants |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 0 Participants |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Positive for ADA | 0 Participants |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Negative for Treatment Emergent ADA | 6 Participants |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Post Baseline: Positive for Treatment Emergent ADA | 0 Participants |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Number of Participants With Anti-Drug Antibodies (ADAs) for Atezolizumab During Study Treatment | Baseline: Negative for ADA | 6 Participants |
Secondary
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).
Population: Efficacy evaluable population included all enrolled participants who received at least one dose of study treatment, regardless of treatment allocation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Overall Survival (OS) | 28.3 months |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Overall Survival (OS) | 20.1 months |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Overall Survival (OS) | NA months |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Overall Survival (OS) | NA months |
Secondary
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
Population: PK evaluable population included all participants who had at least 1 evaluable PK concentration post atezolizumab administration. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at a given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 16 Day 1Pre-Dose | 562000 ng/mL | Geometric Coefficient of Variation 40.3 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 106000 ng/mL | Geometric Coefficient of Variation 12.1 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 376000 ng/mL | Geometric Coefficient of Variation 11.9 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 354000 ng/mL | Geometric Coefficient of Variation 12.2 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 193000 ng/mL | Geometric Coefficient of Variation 85.5 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 347000 ng/mL | Geometric Coefficient of Variation 12.4 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 143000 ng/mL | Geometric Coefficient of Variation 34.3 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 12 Day 1 Pre-Dose | 333000 ng/mL | — |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 330000 ng/mL | Geometric Coefficient of Variation 18.1 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 105000 ng/mL | Geometric Coefficient of Variation 1195.9 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 97400 ng/mL | Geometric Coefficient of Variation 153.2 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 75200 ng/mL | Geometric Coefficient of Variation 170.2 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 16 Day 1Pre-Dose | 408000 ng/mL | Geometric Coefficient of Variation 42 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 12 Day 1 Pre-Dose | 505000 ng/mL | Geometric Coefficient of Variation 14.4 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 90200 ng/mL | Geometric Coefficient of Variation 883.4 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 398000 ng/mL | Geometric Coefficient of Variation 34.4 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 179000 ng/mL | Geometric Coefficient of Variation 256.2 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 Pre-dose | 853 ng/mL | Geometric Coefficient of Variation 1344.8 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 216000 ng/mL | Geometric Coefficient of Variation 50.7 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 135000 ng/mL | Geometric Coefficient of Variation 99.8 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 15 Pre-Dose | 120000 ng/mL | — |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 94500 ng/mL | Geometric Coefficient of Variation 27.8 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 30 min Post-dose | 351000 ng/mL | Geometric Coefficient of Variation 49 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 149000 ng/mL | Geometric Coefficient of Variation 45 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 345000 ng/mL | Geometric Coefficient of Variation 55.9 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 329000 ng/mL | Geometric Coefficient of Variation 25.3 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 283000 ng/mL | Geometric Coefficient of Variation 23.8 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 16 Day 1Pre-Dose | 388000 ng/mL | — |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 239000 ng/mL | Geometric Coefficient of Variation 37 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 315000 ng/mL | Geometric Coefficient of Variation 5.4 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 385000 ng/mL | Geometric Coefficient of Variation 19.2 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 99700 ng/mL | Geometric Coefficient of Variation 118.4 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 93100 ng/mL | Geometric Coefficient of Variation 15.6 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 253000 ng/mL | Geometric Coefficient of Variation 81.9 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 219000 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 30 min Post-dose | 393000 ng/mL | — |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 Pre-dose | 65.3 ng/mL | Geometric Coefficient of Variation 3.4 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 365000 ng/mL | Geometric Coefficient of Variation 19.2 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 91700 ng/mL | Geometric Coefficient of Variation 21 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 132000 ng/mL | Geometric Coefficient of Variation 45 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 15 Pre-Dose | 180000 ng/mL | — |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 246000 ng/mL | Geometric Coefficient of Variation 33 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 283000 ng/mL | Geometric Coefficient of Variation 16.7 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 293000 ng/mL | Geometric Coefficient of Variation 7.1 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 12 Day 1 Pre-Dose | 285000 ng/mL | — |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 195000 ng/mL | Geometric Coefficient of Variation 47.5 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 16 Day 1Pre-Dose | 135000 ng/mL | — |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 337000 ng/mL | Geometric Coefficient of Variation 31.7 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 101000 ng/mL | Geometric Coefficient of Variation 39.1 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 126 ng/mL | — |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 15 Pre-Dose | 124000 ng/mL | Geometric Coefficient of Variation 83.8 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 293000 ng/mL | Geometric Coefficient of Variation 40.3 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 386000 ng/mL | Geometric Coefficient of Variation 32.5 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 166000 ng/mL | Geometric Coefficient of Variation 34.7 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 30 min Post-dose | 362000 ng/mL | Geometric Coefficient of Variation 8.8 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 12 Day 1 Pre-Dose | 122000 ng/mL | — |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 545000 ng/mL | Geometric Coefficient of Variation 29.6 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 12 Day 1 Pre-Dose | 384000 ng/mL | Geometric Coefficient of Variation 11.8 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 30 min Post-dose | 370000 ng/mL | Geometric Coefficient of Variation 9.8 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 230000 ng/mL | Geometric Coefficient of Variation 16.1 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 293000 ng/mL | Geometric Coefficient of Variation 18.3 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 15 Pre-Dose | 189000 ng/mL | Geometric Coefficient of Variation 18.2 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 121000 ng/mL | Geometric Coefficient of Variation 21.6 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 181000 ng/mL | Geometric Coefficient of Variation 40.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 197000 ng/mL | Geometric Coefficient of Variation 32.4 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 147000 ng/mL | Geometric Coefficient of Variation 35.3 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 250000 ng/mL | Geometric Coefficient of Variation 43.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 30 min Post-dose | 274000 ng/mL | — |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 153000 ng/mL | Geometric Coefficient of Variation 119.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 274000 ng/mL | Geometric Coefficient of Variation 113 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 12 Day 1 Pre-Dose | 393000 ng/mL | Geometric Coefficient of Variation 26 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 87100 ng/mL | Geometric Coefficient of Variation 31.6 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 335000 ng/mL | Geometric Coefficient of Variation 13.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 Pre-dose | 82.5 ng/mL | Geometric Coefficient of Variation 7.6 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 15 Pre-Dose | 178000 ng/mL | Geometric Coefficient of Variation 41.7 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 4 Day 1 Pre-Dose | 247000 ng/mL | Geometric Coefficient of Variation 46 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 1 30 min Post-dose | 339000 ng/mL | Geometric Coefficient of Variation 13.6 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Treatment Discontinuation | 178000 ng/mL | Geometric Coefficient of Variation 67.9 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 1 Pre-Dose | 156000 ng/mL | Geometric Coefficient of Variation 20 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 8 Day 1 Pre-Dose | 357000 ng/mL | Geometric Coefficient of Variation 10.3 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 2 Day 15 Pre-Dose | 194000 ng/mL | Geometric Coefficient of Variation 26.1 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 Pre-Dose | 108000 ng/mL | Geometric Coefficient of Variation 32.2 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 3 Day 1 Pre-Dose | 247000 ng/mL | Geometric Coefficient of Variation 9.7 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Atezolizumab | Cycle 1 Day 15 30 min Post-dose | 345000 ng/mL | — |
Secondary
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)
Population: Pharmacokinetic (PK) evaluable population included all participants who had at least 1 evaluable PK concentration post ipatasertib administration. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at a given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 4 hour Post-dose | 226 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.7 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 1 hour Post-dose | 507 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.6 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 318 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21.4 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 47.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.2 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 13.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 783.4 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 1 hour Post-dose | 182 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 167 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 126 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 241.7 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 318 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.8 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 6 hour Post-dose | 182 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.2 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 4 hour Post-dose | 255 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.7 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 421 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.5 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 29.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 163.1 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 1 hour Post-dose | 258 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 127.2 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 196 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 133.7 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 4 hour Post-dose | 305 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.8 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 6 hour Post-dose | 233 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.7 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 287 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.7 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 134 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 82.8 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 6 hour Post-dose | 165 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 4 hour Post-dose | 225 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 30.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37.1 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 1 hour Post-dose | 253 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 128 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 1 hour Post-dose | 219 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 186.6 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 4 hour Post-dose | 266 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.1 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 6 hour Post-dose | 186 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.3 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 214 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 130.8 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 46.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 172.8 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 282 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 235.6 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 Pre-dose | 44.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.3 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 61.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 94.3 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 1 hour Post-dose | 260 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21.6 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 2 hour Post-dose | 575 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.5 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 4 hour Post-dose | 402 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.9 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 6 hour Post-dose | 253 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.7 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 127 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 369 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 2 hour Post-dose | 500 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.3 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 Pre-dose | 50.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.4 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 1 hour Post-dose | 614 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.2 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 6 hour Post-dose | 273 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15.3 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 Pre-dose | 77.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 207 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 155 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 282.3 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 4 hour Post-dose | 340 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 1 hour Post-dose | 232 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 150 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 2 hour Post-dose | 311 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67.5 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 4 hour Post-dose | 258 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20.6 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 233 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 120.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 6 hour Post-dose | 162 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 8.2 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 225 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.9 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 Pre-dose | 29.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 59.5 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 1 Day 15 2 hour Post-dose | 190 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 484.7 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 3 Day 15 1 to 3 hour Post-dose | 382 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 87.9 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 1 hour Post-dose | 364 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 81.4 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 Pre-dose | 31.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53.1 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 2 hour Post-dose | 610 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.7 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 6 hour Post-dose | 234 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.6 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib | Cycle 2 Day 15 4 hour Post-dose | 433 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.7 |
Secondary
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)
Population: PK evaluable population included all participants who had at least 1 evaluable PK concentration post ipatasertib administration. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at a given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 4 hour Post-dose | 118 ng/mL | Geometric Coefficient of Variation 26.1 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 1 hour Post-dose | 200 ng/mL | Geometric Coefficient of Variation 58.3 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 151 ng/mL | Geometric Coefficient of Variation 29.9 |
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 27.0 ng/mL | Geometric Coefficient of Variation 32.4 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 8.27 ng/mL | Geometric Coefficient of Variation 404.3 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 1 hour Post-dose | 61.8 ng/mL | Geometric Coefficient of Variation 209.2 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 47.1 ng/mL | Geometric Coefficient of Variation 238.3 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 124 ng/mL | Geometric Coefficient of Variation 55 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 6 hour Post-dose | 106 ng/mL | Geometric Coefficient of Variation 47.3 |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 4 hour Post-dose | 121 ng/mL | Geometric Coefficient of Variation 41.5 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 153 ng/mL | Geometric Coefficient of Variation 68.8 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 15.0 ng/mL | Geometric Coefficient of Variation 165.9 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 1 hour Post-dose | 85.9 ng/mL | Geometric Coefficient of Variation 119.9 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 69.4 ng/mL | Geometric Coefficient of Variation 161.2 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 4 hour Post-dose | 157 ng/mL | Geometric Coefficient of Variation 62.9 |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 6 hour Post-dose | 133 ng/mL | Geometric Coefficient of Variation 60.3 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 166 ng/mL | Geometric Coefficient of Variation 102.2 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 68.6 ng/mL | Geometric Coefficient of Variation 131.8 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 6 hour Post-dose | 120 ng/mL | Geometric Coefficient of Variation 45.6 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 4 hour Post-dose | 154 ng/mL | Geometric Coefficient of Variation 39.8 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 23.3 ng/mL | Geometric Coefficient of Variation 58.3 |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 1 hour Post-dose | 126 ng/mL | Geometric Coefficient of Variation 158.4 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 1 hour Post-dose | 86.4 ng/mL | Geometric Coefficient of Variation 135.3 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 4 hour Post-dose | 134 ng/mL | Geometric Coefficient of Variation 99.2 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 6 hour Post-dose | 101 ng/mL | Geometric Coefficient of Variation 82.8 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 79.4 ng/mL | Geometric Coefficient of Variation 150.8 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 24.1 ng/mL | Geometric Coefficient of Variation 97.7 |
| Cohort 2-Arm E | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 120 ng/mL | Geometric Coefficient of Variation 193 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 Pre-dose | 22.5 ng/mL | Geometric Coefficient of Variation 27.6 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 30.9 ng/mL | Geometric Coefficient of Variation 48.3 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 1 hour Post-dose | 41.3 ng/mL | Geometric Coefficient of Variation 90.1 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 2 hour Post-dose | 206 ng/mL | Geometric Coefficient of Variation 35.1 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 4 hour Post-dose | 185 ng/mL | Geometric Coefficient of Variation 30.2 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 6 hour Post-dose | 124 ng/mL | Geometric Coefficient of Variation 11.4 |
| Cohort 3-Arm F | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 50.4 ng/mL | Geometric Coefficient of Variation 299.8 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 2 hour Post-dose | 184 ng/mL | Geometric Coefficient of Variation 28 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 Pre-dose | 20.5 ng/mL | Geometric Coefficient of Variation 38.4 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 1 hour Post-dose | 148 ng/mL | Geometric Coefficient of Variation 39.4 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 6 hour Post-dose | 137 ng/mL | Geometric Coefficient of Variation 30.4 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 Pre-dose | 36.4 ng/mL | Geometric Coefficient of Variation 356.1 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 45.0 ng/mL | Geometric Coefficient of Variation 182.3 |
| Cohort 1- Arm C2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 4 hour Post-dose | 146 ng/mL | Geometric Coefficient of Variation 46.5 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 1 hour Post-dose | 70.5 ng/mL | Geometric Coefficient of Variation 244.4 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 2 hour Post-dose | 120 ng/mL | Geometric Coefficient of Variation 171 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 4 hour Post-dose | 131 ng/mL | Geometric Coefficient of Variation 30.8 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 84.6 ng/mL | Geometric Coefficient of Variation 227.5 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 6 hour Post-dose | 98.8 ng/mL | Geometric Coefficient of Variation 77.3 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 78.1 ng/mL | Geometric Coefficient of Variation 125.6 |
| Cohort 1- Arm D1 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 Pre-dose | 15.2 ng/mL | Geometric Coefficient of Variation 81.4 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 1 Day 15 2 hour Post-dose | 177 ng/mL | Geometric Coefficient of Variation 37.1 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 3 Day 15 1 to 3 hour Posst-dose | 144 ng/mL | Geometric Coefficient of Variation 121.6 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 1 hour Post-dose | 140 ng/mL | Geometric Coefficient of Variation 94.2 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 Pre-dose | 24.4 ng/mL | Geometric Coefficient of Variation 76.7 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 2 hour Post-dose | 355 ng/mL | Geometric Coefficient of Variation 22.9 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 6 hour Post-dose | 232 ng/mL | Geometric Coefficient of Variation 57.4 |
| Cohort 1- Arm D2 | Cohort 1 and Cohort 4: Plasma Concentration of Ipatasertib Metabolite M1 (G-037720) | Cycle 2 Day 15 4 hour Post-dose | 402 ng/mL | Geometric Coefficient of Variation 43.4 |
Secondary
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)
Population: Efficacy evaluable population included all enrolled participants who received at least one dose of study treatment, regardless of treatment allocation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1-Arm A | Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1 | 7.2 months |
| Cohort 1-Arm B | Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1 | 6.6 months |
| Cohort 1-Arm C | Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1 | 8.8 months |
| Cohort 1-Arm D | Cohort 1 and Cohort 4: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1 | 6.5 months |