Biliary Cancer, Bladder Cancer, Neoplasms, Salivary Cancer, Solid Tumors
Conditions
Brief summary
This multicenter, non-randomized, open-label study will evaluate the efficacy and safety of six treatment regimens in participants with advanced solid tumors for whom therapies that will convey clinical benefit are not available and/or are not suitable options per the treating physician's judgment.
Interventions
DRUGTrastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGPertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGErlotinib
Erlotinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGVemurafenib
Vemurafenib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGCobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGVismodegib
Vismodegib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGAlectinib
Alectinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
DRUGAtezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
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
General Inclusion Criteria: * Life expectancy greater than or equal to (≥) 12 weeks * Histologically documented metastatic cancer (solid tumors, not including hematologic malignancies) * Participants who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option. Eligible participants should not have available therapies that will convey clinical benefit and/or are not suitable options per the treating physician's judgment * No previous treatment with the specific assigned study drug or any other drug sharing the same target * Measurable disease by RECIST v1.1 * Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 (For patients enrolling in the atezolizumab arm, ECOG score must be documented within 7 days prior to first treatment and confirmation of ECOG PS must be entered into the interactive web response system \[IWRS\] prior to initiation of treatment) * Adequate hematologic, renal, and liver function as defined by the protocol * If applicable, use of contraception methods or abstinence as defined by the protocol Study-Drug Specific Inclusion Criteria: Trastuzumab plus Pertuzumab * Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories (using tissue and/or blood) demonstrating HER2 overexpression or amplification. Participants must have one of the following tumor types: biliary cancer, salivary cancer, or bladder cancer a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment) * Left ventricular ejection fraction (LVEF) greater than (\>) 50 percent (%) or above the lower limit of the institutional normal range, whichever is lower * Availability of an archival or new pre-treatment tissue sample is required if molecular testing was not performed by Foundation Medicine. Any available tumor tissue sample can be submitted. The tissue sample must be submitted within 4 weeks after enrollment Erlotinib * Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating epidermal growth factor receptor (EGFR)-activating mutations Vemurafenib plus Cobimetinib * Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating BRAF V600 mutations a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment) Vismodegib * Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating hedgehog pathway relevant mutation (activating mutation of smoothened \[SMO\] or loss-of-function mutation of protein patched homolog-1 \[PTCH-1\]) a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment) * All non-hematological adverse events related to any prior chemotherapy, surgery, or radiotherapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade less than or equal to (≤) 2 prior to starting therapy Alectinib * Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating anaplastic lymphoma kinase (ALK) gene rearrangements, ALK mutations, ALK copy number gain or (for melanoma only) increased ALK expression or presence of ALK-alternative transcription initiation transcript (ALKATI) a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment) Atezolizumab * Molecular testing results from CLIA-certified laboratories (using tissue) demonstrating elevated tissue tumor mutational burden (tTMB ≥10 mutations/ Megabase \[Mb\]) * For patients where molecular testing was not performed using Foundation Medicine, submission of an archival or new pretreatment tissue sample is mandatory. For patients where molecular testing was performed using Foundation Medicine, submission of an archival or new pretreatment tissue sample is required, if available. The tissue sample must be submitted within 4 weeks after enrollment General
Exclusion criteria
* Participants with hematologic malignancies * Concurrent administration of any other anti-cancer therapy (except male participants with prostate cancer receiving androgen blockade): Bisphosphonates and denosumab are allowed; Most recent anti-cancer therapy ≤28 days and have not recovered from the side effects, excluding alopecia; Radiation therapy within ≤14 days * Active or untreated brain metastases * History of carcinomatous meningitis * Uncontrolled concurrent malignancy (early stage is allowed if not requiring active therapy or intervention) * Pregnant or breastfeeding women, or intending to become pregnant during the study * Any significant cardiovascular events within 6 months prior to study entry * Pulmonary embolism within 30 days prior to study entry * History or presence of clinically significant ventricular or atrial dysrhythmia \>Grade 2 per NCI CTCAE v4.0 * Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol Study-Drug Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | From the date of first study treatment until disease progression or death from any cause, whichever occurs first (72.1 months) | The Objective Response Rate (ORR) is defined as the percentage of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by investigators using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for all arms. |
| Percentage of Atezolizumab-Treated Participants With Tissue Tumor Mutational Burden (tTMB) ≥16 Mutations/Mb With Overall Response, as Assessed by the Independent Review Committee (IRC) | From the date of first study treatment until disease progression or death from any cause, whichever occurs first (68.9 months) | The Objective Response Rate (ORR) is defined as the proportion of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 87.5 months | Overall Survival (OS, months) is defined as the time from the date of the first study treatment (Day 1) to the date of death from any cause. |
| Percentage of Participants With Disease Control | From the date of first study treatment until disease progression or death from any cause, whichever occurs first (72.1 months) | Disease Control Rate (DCR) is defined as the proportion of patients whose best response is CR, PR or stable disease maintained more than 4 months (SD\>4 months). Tumor responses were assessed by investigators using RECIST version 1.1 for all arms. |
| Number of Participants With Adverse Events | From first study treatment administration to 30 days (45 days for vismodegib, 90 days for atezolizumab) after the last dose (up to approximately 6.3 years) | Incidence, nature, and severity of Adverse Events (AE), per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) for participants enrolled prior to Version 6 of the protocol. The NCI CTCAE (v5.0) grading scale was used for assessing AE severity for participants enrolled under Version 6 of the protocol and subsequent versions. |
| Duration of Response (DoR) | From the date of first documented response (complete response [CR] or partial response [PR]) to the time of disease progression or death from any cause, whichever occurs first (70.8 months) | Duration of Response (DoR) is defined as the time from the date of first documented response (CR or PR) to date of first occurrence of disease progression as determined by the investigator, or death from any cause, whichever occurs first. |
| Progression-Free Survival (PFS) | From the date of first study treatment until disease progression as assessed by the investigator, or death from any cause, whichever occurs first (72.1 months) | PFS is defined as the time from the start of study treatment to the first occurrence of disease progression, or death, whichever occurs first. Tumor responses were assessed by investigators using RECIST version 1.1 for all arms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Plus Pertuzumab Participants will receive trastuzumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion as loading dose, followed by 6 mg/kg IV infusion every 3 weeks; and pertuzumab 840 mg IV infusion as loading dose, followed by 420 mg IV infusion every 3 weeks. | 357 |
| Atezolizumab Participants will receive atezolizumab 1200 mg IV infusion every 3 weeks. | 174 |
| Vemurafenib Participants will receive vemurafenib 960 mg orally twice daily (BID) in each 28-day cycle. | 55 |
| Vemurafenib Plus Cobimetinib Participants will receive vemurafenib 960 mg orally twice daily (BID) in each 28-day cycle; and cobimetinib 60 mg orally once daily for 21 days on and 7 days off in each 28-day cycle. | 15 |
| Vismodegib Participants will receive vismodegib 150 mg orally once daily in each 28-day cycle. | 37 |
| Alectinib Participants will receive alectinib 600 mg orally BID in each 28-day cycle. | 21 |
| Erlotinib Participants will receive erlotinib 150 mg orally once daily in each 28-day cycle. | 13 |
| Total | 672 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 280 | 118 | 46 | 13 | 31 | 16 | 12 |
| Overall Study | Lost to Follow-up | 21 | 5 | 1 | 0 | 1 | 2 | 0 |
| Overall Study | Reason Not Specified | 6 | 5 | 2 | 0 | 0 | 0 | 1 |
| Overall Study | Study Ended by Sponsor | 1 | 9 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 21 | 13 | 3 | 2 | 2 | 3 | 0 |
| Overall Study | Withdrew informed consent before receiving study drug | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Atezolizumab | Vemurafenib | Vemurafenib Plus Cobimetinib | Vismodegib | Alectinib | Erlotinib | Trastuzumab Plus Pertuzumab | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 97 Participants | 23 Participants | 9 Participants | 22 Participants | 10 Participants | 7 Participants | 156 Participants | 324 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants | 32 Participants | 6 Participants | 15 Participants | 11 Participants | 6 Participants | 201 Participants | 348 Participants |
| Age, Customized | 65.1 Years STANDARD_DEVIATION 12.33 | 61.3 Years STANDARD_DEVIATION 11.15 | 63.2 Years STANDARD_DEVIATION 8.69 | 63.5 Years STANDARD_DEVIATION 11.41 | 63.5 Years STANDARD_DEVIATION 12.17 | 64.5 Years STANDARD_DEVIATION 13.41 | 61.0 Years STANDARD_DEVIATION 12.06 | 62.4 Years STANDARD_DEVIATION 12.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 19 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 152 Participants | 48 Participants | 12 Participants | 36 Participants | 20 Participants | 12 Participants | 320 Participants | 600 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 18 Participants | 32 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 21 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 7 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 28 Participants | 60 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 16 Participants | 29 Participants |
| Race (NIH/OMB) White | 131 Participants | 46 Participants | 13 Participants | 31 Participants | 18 Participants | 10 Participants | 288 Participants | 537 Participants |
| Sex: Female, Male Female | 98 Participants | 29 Participants | 7 Participants | 16 Participants | 12 Participants | 5 Participants | 179 Participants | 346 Participants |
| Sex: Female, Male Male | 76 Participants | 26 Participants | 8 Participants | 21 Participants | 9 Participants | 8 Participants | 178 Participants | 326 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 285 / 357 | 118 / 174 | 46 / 55 | 13 / 15 | 31 / 37 | 16 / 21 | 12 / 13 |
| other Total, other adverse events | 313 / 357 | 147 / 174 | 50 / 55 | 12 / 15 | 30 / 37 | 20 / 21 | 11 / 13 |
| serious Total, serious adverse events | 95 / 357 | 62 / 174 | 21 / 55 | 11 / 15 | 13 / 37 | 7 / 21 | 3 / 13 |
Outcome results
Primary
Percentage of Atezolizumab-Treated Participants With Tissue Tumor Mutational Burden (tTMB) ≥16 Mutations/Mb With Overall Response, as Assessed by the Independent Review Committee (IRC)
The Objective Response Rate (ORR) is defined as the proportion of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (68.9 months)
Population: The efficacy evaluable population included all atezolizumab-treated participants with tumor mutation burden ≥16 Mutations/Mb and whose tumor responses were assessed by Independent Review Committee (IRC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Plus Pertuzumab | Percentage of Atezolizumab-Treated Participants With Tissue Tumor Mutational Burden (tTMB) ≥16 Mutations/Mb With Overall Response, as Assessed by the Independent Review Committee (IRC) | 29.5 Percentage of Participants |
Primary
Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator
The Objective Response Rate (ORR) is defined as the percentage of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by investigators using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for all arms.
Time frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (72.1 months)
Population: The efficacy evaluable population included all participants who received at least one dose of each drug for their assigned treatment regimen. The population includes the treated participants who have baseline tumor measurement and either have a post-baseline tumor measurement or have discontinued treatment for any reason.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Plus Pertuzumab | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 21.0 Percentage of Participants |
| Atezolizumab | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 19.5 Percentage of Participants |
| Vemurafenib | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 25.5 Percentage of Participants |
| Vemurafenib Plus Cobimetinib | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 33.3 Percentage of Participants |
| Vismodegib | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 10.8 Percentage of Participants |
| Alectinib | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 14.3 Percentage of Participants |
| Erlotinib | Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator | 7.7 Percentage of Participants |
Secondary
Duration of Response (DoR)
Duration of Response (DoR) is defined as the time from the date of first documented response (CR or PR) to date of first occurrence of disease progression as determined by the investigator, or death from any cause, whichever occurs first.
Time frame: From the date of first documented response (complete response [CR] or partial response [PR]) to the time of disease progression or death from any cause, whichever occurs first (70.8 months)
Population: Efficacy evaluable population who have achieved a complete or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Plus Pertuzumab | Duration of Response (DoR) | 7.3 Months |
| Atezolizumab | Duration of Response (DoR) | 32.1 Months |
| Vemurafenib | Duration of Response (DoR) | 6.0 Months |
| Vemurafenib Plus Cobimetinib | Duration of Response (DoR) | 17.2 Months |
| Vismodegib | Duration of Response (DoR) | 14.1 Months |
| Alectinib | Duration of Response (DoR) | 6.6 Months |
| Erlotinib | Duration of Response (DoR) | 8.3 Months |
Secondary
Number of Participants With Adverse Events
Incidence, nature, and severity of Adverse Events (AE), per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) for participants enrolled prior to Version 6 of the protocol. The NCI CTCAE (v5.0) grading scale was used for assessing AE severity for participants enrolled under Version 6 of the protocol and subsequent versions.
Time frame: From first study treatment administration to 30 days (45 days for vismodegib, 90 days for atezolizumab) after the last dose (up to approximately 6.3 years)
Population: The safety (SAF) population is defined as enrolled patients who receive at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 43 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 79 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one non-serious AESI | 5 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 3 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 146 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 17 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one AE | 334 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one AE leading to death | 13 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one SAE | 95 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one Related SAE | 17 Participants |
| Trastuzumab Plus Pertuzumab | Number of Participants With Adverse Events | With at least one Related AE | 261 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one AE | 162 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 25 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one SAE | 62 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one AE leading to death | 5 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 1 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 97 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 45 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one Related AE | 104 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 15 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one Related SAE | 14 Participants |
| Atezolizumab | Number of Participants With Adverse Events | With at least one non-serious AESI | 9 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one SAE | 21 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 25 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one Related AE | 49 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one AE leading to death | 2 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one Related SAE | 6 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one AE | 54 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 37 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 27 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one non-serious AESI | 3 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 28 Participants |
| Vemurafenib | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 10 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 12 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one AE | 15 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one SAE | 11 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one Related AE | 13 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one Related SAE | 5 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 6 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one non-serious AESI | 3 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 3 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 11 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 3 Participants |
| Vemurafenib Plus Cobimetinib | Number of Participants With Adverse Events | With at least one AE leading to death | 2 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one Related SAE | 2 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one non-serious AESI | 0 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one Related AE | 26 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 1 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 21 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one AE | 35 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one AE leading to death | 1 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 11 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one SAE | 13 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 0 Participants |
| Vismodegib | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 8 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 0 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 11 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one Related SAE | 1 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 6 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one SAE | 7 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 4 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one AE leading to death | 0 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one AE | 21 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one non-serious AESI | 0 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one Related AE | 19 Participants |
| Alectinib | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 4 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one AE leading to death | 1 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one Related AE | 9 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one AE | 12 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one Related SAE | 0 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one AE leading to study drug withdrawn | 1 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one AE leading to study drug reduction | 0 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one Grade 3-5 related AE | 1 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one AE leading to study drug interruption | 4 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one SAE | 3 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one Grade 3-5 AE | 4 Participants |
| Erlotinib | Number of Participants With Adverse Events | With at least one non-serious AESI | 0 Participants |
Secondary
Overall Survival (OS)
Overall Survival (OS, months) is defined as the time from the date of the first study treatment (Day 1) to the date of death from any cause.
Time frame: 87.5 months
Population: The efficacy evaluable population included all participants who received at least one dose of each drug for their assigned treatment regimen. The population includes the treated participants who have baseline tumor measurement and either have a post-baseline tumor measurement or have discontinued treatment for any reason.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Plus Pertuzumab | Overall Survival (OS) | 10.1 Months |
| Atezolizumab | Overall Survival (OS) | 13.5 Months |
| Vemurafenib | Overall Survival (OS) | 10.6 Months |
| Vemurafenib Plus Cobimetinib | Overall Survival (OS) | 15.6 Months |
| Vismodegib | Overall Survival (OS) | 9.8 Months |
| Alectinib | Overall Survival (OS) | 14.1 Months |
| Erlotinib | Overall Survival (OS) | 7.7 Months |
Secondary
Percentage of Participants With Disease Control
Disease Control Rate (DCR) is defined as the proportion of patients whose best response is CR, PR or stable disease maintained more than 4 months (SD\>4 months). Tumor responses were assessed by investigators using RECIST version 1.1 for all arms.
Time frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (72.1 months)
Population: The efficacy evaluable population included all participants who received at least one dose of each drug for their assigned treatment regimen. The population includes the treated participants who have baseline tumor measurement and either have a post-baseline tumor measurement or have discontinued treatment for any reason.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Plus Pertuzumab | Percentage of Participants With Disease Control | 41.5 Percentage of Participants |
| Atezolizumab | Percentage of Participants With Disease Control | 39.1 Percentage of Participants |
| Vemurafenib | Percentage of Participants With Disease Control | 34.5 Percentage of Participants |
| Vemurafenib Plus Cobimetinib | Percentage of Participants With Disease Control | 66.7 Percentage of Participants |
| Vismodegib | Percentage of Participants With Disease Control | 16.2 Percentage of Participants |
| Alectinib | Percentage of Participants With Disease Control | 42.9 Percentage of Participants |
| Erlotinib | Percentage of Participants With Disease Control | 23.1 Percentage of Participants |
Secondary
Progression-Free Survival (PFS)
PFS is defined as the time from the start of study treatment to the first occurrence of disease progression, or death, whichever occurs first. Tumor responses were assessed by investigators using RECIST version 1.1 for all arms.
Time frame: From the date of first study treatment until disease progression as assessed by the investigator, or death from any cause, whichever occurs first (72.1 months)
Population: The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen. The population includes the treated participants who have baseline tumor measurement and either have a post-baseline tumor measurement or have discontinued treatment for any reason.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Plus Pertuzumab | Progression-Free Survival (PFS) | 2.8 Months |
| Atezolizumab | Progression-Free Survival (PFS) | 2.7 Months |
| Vemurafenib | Progression-Free Survival (PFS) | 3.1 Months |
| Vemurafenib Plus Cobimetinib | Progression-Free Survival (PFS) | 8.2 Months |
| Vismodegib | Progression-Free Survival (PFS) | 1.8 Months |
| Alectinib | Progression-Free Survival (PFS) | 3.2 Months |
| Erlotinib | Progression-Free Survival (PFS) | 1.8 Months |