Advanced Unresectable or Metastatic Solid Malignancy
Conditions
Brief summary
This is a Phase II, multicenter, non-randomized, open-label, multi-arm study designed to evaluate the safety and efficacy of targeted therapies as single agents or in rational, specified combinations in participants with advanced unresectable or metastatic solid tumors determined to harbor specific biomarkers. Patients will be enrolled based on local testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory. The multi-arm structure of the MyTACTIC study allows patients with solid tumors to be treated with a drug or drug regimen tailored to their biomarker identified at screening.
Interventions
DRUGEntrectinib
Entrectinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 600 milligrams (mg) per day once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.
DRUGInavolisib
Inavolisib will be self-administered by participants orally at home (except on clinic days) at the same time each day, on a starting dose of 9 mg/day QD until disease progression, intolerable toxicity, or consent withdrawal.
DRUGAlectinib
Alectinib will be self-administered by participants orally at home (except on clinic days), at the same times each day, on a starting dose of 600 mg twice a day (BID) until disease progression, intolerable toxicity, or consent withdrawal.
DRUGIpatasertib
Ipatasertib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg QD until disease progression, intolerable toxicity, or consent withdrawal.
DRUGAtezolizumab
Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg for participants on Day 1 of each 21-day cycle until unacceptable toxicity or progressive disease (or loss of clinical benefit).
DRUGTrastuzumab Emtansine
Trastuzumab emtansine will be administered at 3.6 mg per kilogram (kg) of body weight by IV infusion every 21 days (unless dose reduction and/or dose delays are required) until disease progression or unacceptable toxicity.
DRUGPertuzumab, Trastuzumab, and Hyaluronidase-zzxf
PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab once every 3 weeks.
DRUGTucatinib
Tucatinib 300 mg will be administered orally BID continuously starting from Cycle 1 Day 1 onwards.
Chemotherapy will consist of docetaxel, paclitaxel, or capecitabine, as determined by the investigator, and will be administered per the respective package insert and institutional guidelines.
DRUGPaclitaxel
The dose of paclitaxel is 80 mg/m2 administered by IV infusion on Days 1, 8, and 15 of each 28-day cycle. The paclitaxel infusion will be delivered over at least 60 minutes for each dose per institutional guidelines and administered after the oral dose of ipatasertib.
DRUGTiragolumab
Following the administration of atezolizumab and an observation period, participants will receive 600 mg tiragolumab at a fixed dose administered by IV infusion on Day 1 of each 21-day cycle.
DRUGPralsetinib
Pralsetinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg/day (four 100-mg capsules per day) once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.
Sponsors
Genentech, Inc.
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
* Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic solid malignancy * Positive biomarker results from a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory and availability of a full report of the testing results. This may be from a tissue or blood sample. * Evaluable or measurable disease * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Life expectancy ≥8 weeks * Adequate hematologic and end-organ function, as defined in the protocol, obtained within 14 days prior to initiation of study treatment * Agrees to take measures to prevent pregnancy in the patient or partner * In addition to the general inclusion criteria above, there are treatment-specific inclusion criteria that apply for each respective treatment arm (as detailed in the protocol)
Exclusion criteria
* Current participation or enrollment in another therapeutic clinical trial * Symptomatic or actively progressing CNS metastases (asymptomatic patients with treated or untreated CNS metastases may be eligible, provided all protocol-defined criteria are met) * History of leptomeningeal disease, unless noted otherwise for a specific treatment arm of the study * Wide field radiotherapy within 14 days prior to start of study treatment * Stereotactic radiosurgery within 7 days prior to start of study treatment * Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact patient safety * Receipt of any anticancer drug/biologic or investigational treatment 21 days prior to Cycle 1, Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1, Day 1 (androgen blockage may be continued for male patients with prostate cancer) * Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection with status outside of study-allowed criteria * History of or concurrent serious medical condition or abnormality in clinical laboratory tests that precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study * History of malignancy other than disease under study within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death * Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment * Major surgical procedure, other than for diagnosis, or significant traumatic injury within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study * Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina * Pregnant or breastfeeding, or intending to become pregnant during the study * In addition to the general
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | Up to 32 months | Confirmed objective response rate (cORR)=percentage of participants with best response as complete response (CR) or partial response (PR) for measurable disease & CR for non-measurable disease. Confirmation=CR/PR on 2 consecutive visits ≥4 weeks apart for 3-week cycles & ≥6 weeks apart for 4-week cycles. Per RECIST, CR=disappearance of all target lesions. PR= ≥30% decrease in sum of diameters of target lesions, in absence of CR. Per RANO, CR=complete disappearance of all measurable & non-measurable disease for ≥4 weeks; no new lesions/abnormality on T2/FLAIR imaging; stable/improved non-enhancing lesions; participants must be off corticosteroids or on physiological doses; clinical status stable/improved. PR= ≥50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions on T2/FLAIR imaging for ≥4 weeks; no progression of non-measurable T1 disease; stable/improved non-enhancing lesions; corticosteroid dose ≤ baseline; clinical status stable/improved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | Time from start of treatment to the first occurrence of disease progression or death from any cause (Up to 32 months) | PFS=time from start of treatment to the first occurrence of disease progression (PD) or death from any cause, whichever occurs first, per RECIST v1.1, or RANO. Per RECIST, PD=≥20% increase in sum of diameters of lesions, using the smallest sum during the study as reference, including baseline (BL). Per RANO, PD= ≥25% increase in sum of products of perpendicular diameters of enhancing lesions compared to smallest tumor measurement at BL/best response, on stable/increasing corticosteroids (CS) dose; Significant/ ≥25% increase of T2/FLAIR non-enhancing lesion on stable/increasing CS dose compared to BL/best response after therapy start; Presence of new lesions/increase of enhancement; Clear progression of non-measurable disease; Definite clinical deterioration only due to tumor/decrease in CS dose; Failure to return for evaluation due to death/deterioration. Kaplan-Meier methodology was used to estimate PFS; patients without an event were censored on the last available assessment day. |
| Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | Time from the date of the first confirmed CR/PR to PD or death from any cause (Up to 32 months) | DOR was defined as the time from the date of the first confirmed complete response (CR) or partial response (PR) to disease progression (PD) or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. CR & PR were defined per RECIST or RANO as outlined in the description for the cORR outcome measure (OM). PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Kaplan-Meier methodology was used to estimate the median DOR. The 95% confidence intervals for the median DOR were computed by the method of Brookmeyer and Crowley. Participants who did not experience death or PD were censored on the day of the last available assessment. |
| PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | At Months 3, 6, 9 and 12 | The PFS rates were calculated using the Kaplan-Meier (KM) method to estimate the percent survival probability of participants (i.e., PFS event-free: did not experience PD or death from any cause) in each treatment arm at landmark timepoints. The 95% confidence intervals for each PFS rate were computed by the method of Greenwood. PFS was defined as the time from the start of study treatment to the first occurrence of PD or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Participants who did not experience death or PD were censored on the day of the last available assessment. The number analyzed per landmark timepoint actually represents the number of participants who remained at risk of experiencing a PFS event at that timepoint. Percentages are rounded off to the nearest decimal point. |
| Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | Up to 32 months | Disease control rate was defined as the percentage of participants whose best response was confirmed CR, confirmed PR, or a response of CR, PR, stable disease (SD), or non-CR/non-PD for a minimum of 98 days for 28-day cycle arms or 70 days for 21-day cycle arms after the first treatment date. CR & PR were defined per RECIST/RANO as outlined in the description for the cORR OM. SD per RECIST: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. SD per RANO: Participant does not qualify for CR, PR, or minor response or PD; Stable non-enhancing (T2/FLAIR) lesions or abnormalities on same or lower dose of corticosteroids compared to baseline; No new lesions or new T2 or FLAIR abnormalities apart from those consistent with radiation effect, & no new or increased enhancement; Participants on a should be corticosteroid dose that is not greater than dose at baseline scan & is stable or improved clinically; Clinical status, stable/improved. |
| Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | From initiation of study drug until 28 days after the final dose of study drugs other than atezolizumab and until 90 days after the final dose of atezolizumab (Up to 32 months) | An AE is an untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with the product. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to it. AEs were graded for severity according to NCI CTCAE v5.0. Grade 1= Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3 = Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4= Life-threatening consequences/urgent intervention indicated; Grade 5= Death related to adverse event. |
Countries
United States
Participant flow
Recruitment details
A total of 252 participants with advanced unresectable or metastatic solid tumors with positive biomarker result took part in the study across 38 investigative sites in the United States.
Pre-assignment details
Participants in this multi-arm study were treated with a drug or drug regimen tailored to their biomarker identified at screening. A total of 15 arms (Arms A to O) were planned for this study. However, no participants were enrolled in Arm A.
Participants by arm
| Arm | Count |
|---|---|
| Arm B: Inavolisib (GDC-0077) Participants with a positive tumor biomarker result for PIK3CA activating mutation self-administered inavolisib 9 mg, orally, QD until disease progression, intolerable toxicity, or consent withdrawal whichever occurs first. | 26 |
| Arm C: Alectinib Participants with a positive tumor biomarker result for ALK gene fusion self-administered alectinib, 600 mg, orally, BID until disease progression, intolerable toxicity, or consent withdrawal, whichever occurs first. | 5 |
| Arm D: Ipatasertib Participants with a positive tumor biomarker result for phosphatase and tensin homolog (PTEN) loss/loss-of-function or protein kinase B (AKT) activating mutation self-administered ipatasertib, 400 mg orally, QD until disease progression, intolerable toxicity, or consent withdrawal, whichever occurs first. | 26 |
| Arm E: Atezolizumab + Chemotherapy Participants with a positive tumor biomarker result for TMB-H or MSI-H or dMMR received atezolizumab, 1200 mg, as IV infusion, on Day 1 of each 21-day cycle in combination with investigators choice of chemotherapy (docetaxel, paclitaxel, or capecitabine) until disease progression, loss of clinical benefit, or unacceptable toxicity whichever occurs first. | 25 |
| Arm F: Trastuzumab Emtansine + Atezolizumab Participants with a positive tumor biomarker result for human epidermal growth factor receptor 2 (HER2) gene amplification or mutation without known TMB-H/ MSI-H/ dMMR received atezolizumab, 1200 mg, as IV infusion, on Day 1 of each 21-day cycle, followed by trastuzumab emtansine, 3.6 milligrams/kilograms (mg/kg), as IV infusion, every 21 days until disease progression, loss of clinical benefit, or unacceptable toxicity, whichever occurs first. | 25 |
| Arm G: PH FDC SC Participants with a positive tumor biomarker result for HER2 gene amplification or mutation without known TMB-H/ MSI-H/ dMMR received PH FDC SC, a loading dose of 1200 mg pertuzumab + 600 mg trastuzumab as subcutaneous (SC) injection on Day 1 of Cycle 1 followed by a maintenance dose of 600 mg pertuzumab + 600 mg trastuzumab as a SC injection on Day 1 of each 21-day cycle, starting at Cycle 2. | 13 |
| Arm H: PH FDC SC + Chemotherapy Participants with a positive tumor biomarker result for HER2 gene amplification or mutation without known TMB-H/ MSI-H/ dMMR received PH FDC SC, a loading dose of 1200 mg pertuzumab + 600 mg trastuzumab as a SC injection on Day 1 of Cycle 1 followed by a maintenance dose of 600 mg pertuzumab + 600 mg trastuzumab as a SC injection on Day 1 of each 21-day cycle, starting at Cycle 2 in combination with investigators choice of chemotherapy (docetaxel, paclitaxel, or capecitabine). | 8 |
| Arm I: Trastuzumab Emtansine + Tucatinib Participants with a positive tumor biomarker result for HER2 gene amplification or mutation without known TMB-H/ MSI-H/ dMMR received trastuzumab emtansine, 3.6 mg/kg as IV infusion, every 21 days in combination with tucatinib, 300 mg, orally, BID starting from Cycle 1 Day 1 until disease progression or unacceptable toxicity, whichever occurs first. | 23 |
| Arm J: Trastuzumab Emtansine + Atezolizumab Participants with a positive tumor biomarker result for HER2 gene amplification or mutation plus TMB-H/ MSI-H/ dMMR received atezolizumab, 1200 mg, as IV infusion, on Day 1 of each 21-day cycle, followed by trastuzumab emtansine, 3.6 mg/kg, as IV infusion, every 21 days until disease progression, loss of clinical benefit, or unacceptable toxicity, whichever occurs first. | 19 |
| Arm K: Ipatasertib + Atezolizumab Participants with a positive tumor biomarker result for PIK3CA activating mutation received ipatasertib, 400 mg, orally QD in combination with atezolizumab, 1200 mg, as IV infusion, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity, whichever occurs first. | 28 |
| Arm L: Ipatasertib + Atezolizumab Participants with a positive tumor biomarker result for PTEN loss/loss-of-function or AKT-activating mutation self-administered ipatasertib, 400 mg, orally, QD and received atezolizumab, 1200 mg, as IV infusion, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or intolerable toxicity, whichever occurs first. | 25 |
| Arm M: Ipatasertib + Paclitaxel Participants with a positive tumor biomarker result for co-mutations in PIK3CA activating mutations and PTEN loss/loss-of-function or AKT-activating mutation self-administered ipatasertib, 400 mg, orally, QD on Days 1 to 21 of 28-day cycles and received paclitaxel, 80 mg/m\^2, as IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, or consent withdrawal, whichever occurs first. | 3 |
| Arm N: Atezolizumab + Tiragolumab Participants with a positive tumor biomarker result for TMB-H/ MSI-H/ dMMR received atezolizumab, 1200 mg, as IV infusion, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity, whichever occurs first. | 23 |
| Arm O: Pralsetinib Participants with a positive tumor biomarker result for RET gene fusion self-administered pralsetinib, 400 mg, orally, QD until disease progression, intolerable toxicity, or consent withdrawal whichever occurs first. | 3 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Death | 17 | 1 | 14 | 14 | 13 | 6 | 7 | 12 | 15 | 20 | 8 | 2 | 10 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 1 | 1 | 1 | 2 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 |
| Overall Study | Reason not Specified | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 5 | 4 | 3 | 3 | 0 | 5 | 0 | 2 | 8 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Arm B: Inavolisib (GDC-0077) | Arm C: Alectinib | Arm D: Ipatasertib | Arm E: Atezolizumab + Chemotherapy | Arm F: Trastuzumab Emtansine + Atezolizumab | Arm G: PH FDC SC | Arm H: PH FDC SC + Chemotherapy | Arm I: Trastuzumab Emtansine + Tucatinib | Arm J: Trastuzumab Emtansine + Atezolizumab | Arm K: Ipatasertib + Atezolizumab | Arm L: Ipatasertib + Atezolizumab | Arm M: Ipatasertib + Paclitaxel | Arm N: Atezolizumab + Tiragolumab | Arm O: Pralsetinib | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 11.5 | 62.6 years STANDARD_DEVIATION 6.7 | 66.7 years STANDARD_DEVIATION 10 | 66.0 years STANDARD_DEVIATION 12 | 66.1 years STANDARD_DEVIATION 12.9 | 63.8 years STANDARD_DEVIATION 10.7 | 61.1 years STANDARD_DEVIATION 12.8 | 64.2 years STANDARD_DEVIATION 12 | 61.8 years STANDARD_DEVIATION 10.7 | 60.3 years STANDARD_DEVIATION 10.4 | 59.8 years STANDARD_DEVIATION 11.4 | 57.7 years STANDARD_DEVIATION 19.4 | 63.7 years STANDARD_DEVIATION 11 | 71.3 years STANDARD_DEVIATION 16.2 | 63.6 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 5 Participants | 24 Participants | 24 Participants | 24 Participants | 12 Participants | 6 Participants | 20 Participants | 17 Participants | 26 Participants | 25 Participants | 3 Participants | 20 Participants | 3 Participants | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 4 Participants | 0 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) White | 24 Participants | 5 Participants | 21 Participants | 24 Participants | 20 Participants | 12 Participants | 4 Participants | 20 Participants | 12 Participants | 24 Participants | 23 Participants | 3 Participants | 19 Participants | 3 Participants | 214 Participants |
| Sex: Female, Male Female | 18 Participants | 4 Participants | 18 Participants | 11 Participants | 8 Participants | 7 Participants | 5 Participants | 15 Participants | 9 Participants | 19 Participants | 15 Participants | 2 Participants | 14 Participants | 1 Participants | 146 Participants |
| Sex: Female, Male Male | 8 Participants | 1 Participants | 8 Participants | 14 Participants | 17 Participants | 6 Participants | 3 Participants | 8 Participants | 10 Participants | 9 Participants | 10 Participants | 1 Participants | 9 Participants | 2 Participants | 106 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 26 | 1 / 5 | 16 / 26 | 16 / 25 | 16 / 25 | 6 / 13 | 8 / 8 | 14 / 23 | 16 / 19 | 22 / 28 | 10 / 25 | 2 / 3 | 10 / 23 | 1 / 3 |
| other Total, other adverse events | 25 / 26 | 5 / 5 | 25 / 26 | 25 / 25 | 23 / 25 | 11 / 13 | 8 / 8 | 23 / 23 | 19 / 19 | 26 / 28 | 25 / 25 | 3 / 3 | 21 / 23 | 3 / 3 |
| serious Total, serious adverse events | 5 / 26 | 2 / 5 | 6 / 26 | 11 / 25 | 9 / 25 | 2 / 13 | 2 / 8 | 6 / 23 | 7 / 19 | 10 / 28 | 8 / 25 | 2 / 3 | 6 / 23 | 2 / 3 |
Outcome results
Primary
Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors
Confirmed objective response rate (cORR)=percentage of participants with best response as complete response (CR) or partial response (PR) for measurable disease & CR for non-measurable disease. Confirmation=CR/PR on 2 consecutive visits ≥4 weeks apart for 3-week cycles & ≥6 weeks apart for 4-week cycles. Per RECIST, CR=disappearance of all target lesions. PR= ≥30% decrease in sum of diameters of target lesions, in absence of CR. Per RANO, CR=complete disappearance of all measurable & non-measurable disease for ≥4 weeks; no new lesions/abnormality on T2/FLAIR imaging; stable/improved non-enhancing lesions; participants must be off corticosteroids or on physiological doses; clinical status stable/improved. PR= ≥50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions on T2/FLAIR imaging for ≥4 weeks; no progression of non-measurable T1 disease; stable/improved non-enhancing lesions; corticosteroid dose ≤ baseline; clinical status stable/improved.
Time frame: Up to 32 months
Population: Efficacy population included all participants who received at least one dose of study treatment and either had at least one post-baseline tumor assessment or discontinued treatment for any reason. Percentages have been rounded off to the nearest decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Inavolisib (GDC-0077) | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 11.5 percentage of participants |
| Arm C: Alectinib | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 20.0 percentage of participants |
| Arm D: Ipatasertib | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 11.5 percentage of participants |
| Arm E: Atezolizumab + Chemotherapy | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 28.0 percentage of participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 12.0 percentage of participants |
| Arm G: PH FDC SC | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 0.0 percentage of participants |
| Arm H: PH FDC SC + Chemotherapy | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 0.0 percentage of participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 13.0 percentage of participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 0.0 percentage of participants |
| Arm K: Ipatasertib + Atezolizumab | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 0.0 percentage of participants |
| Arm L: Ipatasertib + Atezolizumab | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 0.0 percentage of participants |
| Arm M: Ipatasertib + Paclitaxel | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 66.7 percentage of participants |
| Arm N: Atezolizumab + Tiragolumab | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 21.7 percentage of participants |
| Arm O: Pralsetinib | Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors | 33.3 percentage of participants |
Secondary
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria
DOR was defined as the time from the date of the first confirmed complete response (CR) or partial response (PR) to disease progression (PD) or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. CR & PR were defined per RECIST or RANO as outlined in the description for the cORR outcome measure (OM). PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Kaplan-Meier methodology was used to estimate the median DOR. The 95% confidence intervals for the median DOR were computed by the method of Brookmeyer and Crowley. Participants who did not experience death or PD were censored on the day of the last available assessment.
Time frame: Time from the date of the first confirmed CR/PR to PD or death from any cause (Up to 32 months)
Population: Efficacy population included all participants who received at least one dose of study treatment and either had at least one post-baseline tumor assessment or discontinued treatment for any reason. Participants who achieved a confirmed CR/PR were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Inavolisib (GDC-0077) | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 5.6 months |
| Arm C: Alectinib | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6.5 months |
| Arm D: Ipatasertib | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 5.5 months |
| Arm E: Atezolizumab + Chemotherapy | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | NA months |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 20.0 months |
| Arm I: Trastuzumab Emtansine + Tucatinib | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 7.6 months |
| Arm M: Ipatasertib + Paclitaxel | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 5.5 months |
| Arm N: Atezolizumab + Tiragolumab | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | NA months |
| Arm O: Pralsetinib | Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | NA months |
Secondary
Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
An AE is an untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with the product. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to it. AEs were graded for severity according to NCI CTCAE v5.0. Grade 1= Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3 = Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4= Life-threatening consequences/urgent intervention indicated; Grade 5= Death related to adverse event.
Time frame: From initiation of study drug until 28 days after the final dose of study drugs other than atezolizumab and until 90 days after the final dose of atezolizumab (Up to 32 months)
Population: Safety evaluable population included all participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm B: Inavolisib (GDC-0077) | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm B: Inavolisib (GDC-0077) | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 25 Participants |
| Arm B: Inavolisib (GDC-0077) | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 6 Participants |
| Arm B: Inavolisib (GDC-0077) | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 2 Participants |
| Arm B: Inavolisib (GDC-0077) | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 14 Participants |
| Arm B: Inavolisib (GDC-0077) | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 3 Participants |
| Arm C: Alectinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 5 Participants |
| Arm C: Alectinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 2 Participants |
| Arm C: Alectinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 2 Participants |
| Arm C: Alectinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm C: Alectinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 0 Participants |
| Arm C: Alectinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 1 Participants |
| Arm D: Ipatasertib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 9 Participants |
| Arm D: Ipatasertib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 14 Participants |
| Arm D: Ipatasertib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 25 Participants |
| Arm D: Ipatasertib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 1 Participants |
| Arm D: Ipatasertib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm D: Ipatasertib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 1 Participants |
| Arm E: Atezolizumab + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 11 Participants |
| Arm E: Atezolizumab + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 25 Participants |
| Arm E: Atezolizumab + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 4 Participants |
| Arm E: Atezolizumab + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 0 Participants |
| Arm E: Atezolizumab + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 1 Participants |
| Arm E: Atezolizumab + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 9 Participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 11 Participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 24 Participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 10 Participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 3 Participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm G: PH FDC SC | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm G: PH FDC SC | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 2 Participants |
| Arm G: PH FDC SC | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm G: PH FDC SC | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 3 Participants |
| Arm G: PH FDC SC | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 6 Participants |
| Arm G: PH FDC SC | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 11 Participants |
| Arm H: PH FDC SC + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 1 Participants |
| Arm H: PH FDC SC + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 8 Participants |
| Arm H: PH FDC SC + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 3 Participants |
| Arm H: PH FDC SC + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 4 Participants |
| Arm H: PH FDC SC + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm H: PH FDC SC + Chemotherapy | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 4 Participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 0 Participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 11 Participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 1 Participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 23 Participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 7 Participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 19 Participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 0 Participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 11 Participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 1 Participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 7 Participants |
| Arm K: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 27 Participants |
| Arm K: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 7 Participants |
| Arm K: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 16 Participants |
| Arm K: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 1 Participants |
| Arm K: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 1 Participants |
| Arm K: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 2 Participants |
| Arm L: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 2 Participants |
| Arm L: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm L: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 25 Participants |
| Arm L: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 10 Participants |
| Arm L: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 2 Participants |
| Arm L: Ipatasertib + Atezolizumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 11 Participants |
| Arm M: Ipatasertib + Paclitaxel | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 0 Participants |
| Arm M: Ipatasertib + Paclitaxel | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 3 Participants |
| Arm M: Ipatasertib + Paclitaxel | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm M: Ipatasertib + Paclitaxel | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 3 Participants |
| Arm M: Ipatasertib + Paclitaxel | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 0 Participants |
| Arm M: Ipatasertib + Paclitaxel | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 0 Participants |
| Arm N: Atezolizumab + Tiragolumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 11 Participants |
| Arm N: Atezolizumab + Tiragolumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 8 Participants |
| Arm N: Atezolizumab + Tiragolumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 1 Participants |
| Arm N: Atezolizumab + Tiragolumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 1 Participants |
| Arm N: Atezolizumab + Tiragolumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 21 Participants |
| Arm N: Atezolizumab + Tiragolumab | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
| Arm O: Pralsetinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 3 Participants |
| Arm O: Pralsetinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 3 AEs | 2 Participants |
| Arm O: Pralsetinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 5 AEs | 1 Participants |
| Arm O: Pralsetinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 1 AEs | 0 Participants |
| Arm O: Pralsetinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 2 AEs | 0 Participants |
| Arm O: Pralsetinib | Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Highest Severity: Grade 4 AEs | 0 Participants |
Secondary
Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria
Disease control rate was defined as the percentage of participants whose best response was confirmed CR, confirmed PR, or a response of CR, PR, stable disease (SD), or non-CR/non-PD for a minimum of 98 days for 28-day cycle arms or 70 days for 21-day cycle arms after the first treatment date. CR & PR were defined per RECIST/RANO as outlined in the description for the cORR OM. SD per RECIST: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. SD per RANO: Participant does not qualify for CR, PR, or minor response or PD; Stable non-enhancing (T2/FLAIR) lesions or abnormalities on same or lower dose of corticosteroids compared to baseline; No new lesions or new T2 or FLAIR abnormalities apart from those consistent with radiation effect, & no new or increased enhancement; Participants on a should be corticosteroid dose that is not greater than dose at baseline scan & is stable or improved clinically; Clinical status, stable/improved.
Time frame: Up to 32 months
Population: Efficacy population included all participants who received at least one dose of study treatment and either had at least one post-baseline tumor assessment or discontinued treatment for any reason. Percentages have been rounded off to the nearest decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Inavolisib (GDC-0077) | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 57.7 percentage of participants |
| Arm C: Alectinib | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 40.0 percentage of participants |
| Arm D: Ipatasertib | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 34.6 percentage of participants |
| Arm E: Atezolizumab + Chemotherapy | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 32.0 percentage of participants |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 52.0 percentage of participants |
| Arm G: PH FDC SC | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 23.1 percentage of participants |
| Arm H: PH FDC SC + Chemotherapy | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 37.5 percentage of participants |
| Arm I: Trastuzumab Emtansine + Tucatinib | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 26.1 percentage of participants |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 15.8 percentage of participants |
| Arm K: Ipatasertib + Atezolizumab | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 10.7 percentage of participants |
| Arm L: Ipatasertib + Atezolizumab | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 32.0 percentage of participants |
| Arm M: Ipatasertib + Paclitaxel | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 66.7 percentage of participants |
| Arm N: Atezolizumab + Tiragolumab | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 47.8 percentage of participants |
| Arm O: Pralsetinib | Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 66.7 percentage of participants |
Secondary
PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria
The PFS rates were calculated using the Kaplan-Meier (KM) method to estimate the percent survival probability of participants (i.e., PFS event-free: did not experience PD or death from any cause) in each treatment arm at landmark timepoints. The 95% confidence intervals for each PFS rate were computed by the method of Greenwood. PFS was defined as the time from the start of study treatment to the first occurrence of PD or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Participants who did not experience death or PD were censored on the day of the last available assessment. The number analyzed per landmark timepoint actually represents the number of participants who remained at risk of experiencing a PFS event at that timepoint. Percentages are rounded off to the nearest decimal point.
Time frame: At Months 3, 6, 9 and 12
Population: Efficacy population included all participants who received at least one dose of study treatment and either had at least one post-baseline tumor assessment or discontinued treatment for any reason. The number analyzed per timepoint is the number of participants (out of the overall number of participants analyzed for PFS per arm) who remained at risk for a PFS event at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm B: Inavolisib (GDC-0077) | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 57.69 percent probability |
| Arm B: Inavolisib (GDC-0077) | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 20.60 percent probability |
| Arm B: Inavolisib (GDC-0077) | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 37.09 percent probability |
| Arm B: Inavolisib (GDC-0077) | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 16.48 percent probability |
| Arm C: Alectinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 50.00 percent probability |
| Arm C: Alectinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 25.00 percent probability |
| Arm C: Alectinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 50.00 percent probability |
| Arm D: Ipatasertib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 4.50 percent probability |
| Arm D: Ipatasertib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 9.00 percent probability |
| Arm D: Ipatasertib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 36.00 percent probability |
| Arm D: Ipatasertib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 52.00 percent probability |
| Arm E: Atezolizumab + Chemotherapy | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 18.97 percent probability |
| Arm E: Atezolizumab + Chemotherapy | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 52.17 percent probability |
| Arm E: Atezolizumab + Chemotherapy | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 28.46 percent probability |
| Arm E: Atezolizumab + Chemotherapy | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 33.20 percent probability |
| Arm F: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 44.00 percent probability |
| Arm F: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 32.00 percent probability |
| Arm F: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 64.00 percent probability |
| Arm F: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 23.33 percent probability |
| Arm G: PH FDC SC | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 41.03 percent probability |
| Arm G: PH FDC SC | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 20.51 percent probability |
| Arm G: PH FDC SC | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 10.26 percent probability |
| Arm H: PH FDC SC + Chemotherapy | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 12.50 percent probability |
| Arm H: PH FDC SC + Chemotherapy | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 50.00 percent probability |
| Arm I: Trastuzumab Emtansine + Tucatinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 33.69 percent probability |
| Arm I: Trastuzumab Emtansine + Tucatinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 19.25 percent probability |
| Arm I: Trastuzumab Emtansine + Tucatinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 48.13 percent probability |
| Arm I: Trastuzumab Emtansine + Tucatinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 9.63 percent probability |
| Arm J: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 10.53 percent probability |
| Arm J: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 10.53 percent probability |
| Arm J: Trastuzumab Emtansine + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 26.32 percent probability |
| Arm K: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 35.56 percent probability |
| Arm K: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 11.85 percent probability |
| Arm K: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 3.95 percent probability |
| Arm L: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 33.82 percent probability |
| Arm L: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 65.22 percent probability |
| Arm L: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 24.15 percent probability |
| Arm L: Ipatasertib + Atezolizumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 14.49 percent probability |
| Arm M: Ipatasertib + Paclitaxel | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 66.67 percent probability |
| Arm M: Ipatasertib + Paclitaxel | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 33.33 percent probability |
| Arm N: Atezolizumab + Tiragolumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 9 months | 36.36 percent probability |
| Arm N: Atezolizumab + Tiragolumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 59.09 percent probability |
| Arm N: Atezolizumab + Tiragolumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 12 months | 36.36 percent probability |
| Arm N: Atezolizumab + Tiragolumab | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 40.91 percent probability |
| Arm O: Pralsetinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3 months | 66.67 percent probability |
| Arm O: Pralsetinib | PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 6 months | 66.67 percent probability |
Secondary
Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria
PFS=time from start of treatment to the first occurrence of disease progression (PD) or death from any cause, whichever occurs first, per RECIST v1.1, or RANO. Per RECIST, PD=≥20% increase in sum of diameters of lesions, using the smallest sum during the study as reference, including baseline (BL). Per RANO, PD= ≥25% increase in sum of products of perpendicular diameters of enhancing lesions compared to smallest tumor measurement at BL/best response, on stable/increasing corticosteroids (CS) dose; Significant/ ≥25% increase of T2/FLAIR non-enhancing lesion on stable/increasing CS dose compared to BL/best response after therapy start; Presence of new lesions/increase of enhancement; Clear progression of non-measurable disease; Definite clinical deterioration only due to tumor/decrease in CS dose; Failure to return for evaluation due to death/deterioration. Kaplan-Meier methodology was used to estimate PFS; patients without an event were censored on the last available assessment day.
Time frame: Time from start of treatment to the first occurrence of disease progression or death from any cause (Up to 32 months)
Population: Efficacy population included all participants who received at least one dose of study treatment and either had at least one post-baseline tumor assessment or discontinued treatment for any reason. Participants who did not experience death or disease progression were censored on the day of the last available assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Inavolisib (GDC-0077) | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 4.24 months |
| Arm C: Alectinib | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 4.98 months |
| Arm D: Ipatasertib | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3.48 months |
| Arm E: Atezolizumab + Chemotherapy | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3.94 months |
| Arm F: Trastuzumab Emtansine + Atezolizumab | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 4.73 months |
| Arm G: PH FDC SC | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 2.46 months |
| Arm H: PH FDC SC + Chemotherapy | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3.02 months |
| Arm I: Trastuzumab Emtansine + Tucatinib | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 2.69 months |
| Arm J: Trastuzumab Emtansine + Atezolizumab | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 1.87 months |
| Arm K: Ipatasertib + Atezolizumab | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 2.10 months |
| Arm L: Ipatasertib + Atezolizumab | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 3.61 months |
| Arm M: Ipatasertib + Paclitaxel | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 5.98 months |
| Arm N: Atezolizumab + Tiragolumab | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 4.76 months |
| Arm O: Pralsetinib | Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria | 7.10 months |