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.
Name: Trastuzumab
Name: Pertuzumab
Name: Erlotinib
Name: Vemurafenib
Name: Cobimetinib
Name: Vismodegib
Name: Alectinib
Name: Atezolizumab
Description: Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for all arms.
Measure: Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator Time: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)Description: Tumor response will be assessed using RECIST version 1.1.
Measure: 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) Time: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)Description: Tumor response will be assessed using RECIST version 1.1 for all arms.
Measure: Percentage of Participants With Disease Control Time: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)Description: Tumor response will be assessed using RECIST version 1.1 for all arms.
Measure: Progression-Free Survival (PFS) Time: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)Description: Tumor response will be assessed using RECIST version 1.1 for all arms.
Measure: Duration of Response Time: 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 (up to approximately 5 years)Description: Tumor response will be assessed using RECIST version 1.1.
Measure: Percentage of Atezolizumab-Treated Participants with tTMB ≥10 Mutations/Mb and <16 Mutations/Mb With Overall Response, as Assessed by the Investigator Time: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)Description: Tumor response will be assessed using RECIST version 1.1.
Measure: Percentage of Atezolizumab-Treated Participants with Blood Tumor Mutational Burden (bTMB) ≥16 Mutations With Overall Response, as Assessed by the IRC Time: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)Allocation: Non-Randomized
Parallel Assignment
There is one SNP
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 Exclusion Criteria: Trastuzumab plus Pertuzumab - Previous treatment with any HER2-targeted therapy Erlotinib - Non-small cell lung cancer (NSCLC) or pancreatic cancer identified by exon 19 deletions or exon 21 L858R substitution mutations - EGFR amplifications in the absence of EGFR-activating mutations - Cancers with exon 20 mutations - Previous treatment with erlotinib or any other EGFR inhibitor - Inability to swallow pills - Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of erlotinib Vemurafenib plus Cobimetinib - Malignant melanoma, papillary thyroid cancer, colorectal cancer, or hematologic malignancy including multiple myeloma - LVEF below institutional lower level of normal (LLN) or below 50%, whichever is lower - History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration - Presence of any of the following conditions, which are risk factors for RVO: Uncontrolled glaucoma with intraocular pressure >21 millimetres of mercury (mm Hg); Serum cholesterol ≥Grade 2; Hypertriglyceridemia ≥Grade 2; Hyperglycemia (fasting) ≥Grade 2; Grade ≥2 uncontrolled hypertension (participants with a history of hypertension controlled with anti-hypertensive medication to Grade =1 are eligible) - Prior or concurrent malignancy with known RAS mutation - Previous treatment with vemurafenib or any other BRAF inhibitor (prior sorafenib is allowed) - Previous treatment with cobimetinib or any other mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor - Prior treatment with a RAF inhibitor - Inability to swallow pills - Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of vemurafenib - History of congenital long QT syndrome or mean (average of triplicate measurements) corrected QT (QTc) measured using Fridericia's method ≥450 millisecond (ms) at baseline or uncorrectable abnormalities in serum electrolytes (sodium, potassium, calcium, magnesium, phosphorus) Vismodegib - Basal cell carcinoma of the skin, medulloblastoma, small-cell lung cancer, or hematologic malignancies - Previous treatment with vismodegib or any other hedgehog pathway inhibitor - Inability to swallow pills - Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of vismodegib Alectinib - ALK-positive NSCLC, neuroblastoma, and childhood tumors - Previous treatment with alectinib or any other ALK inhibitor - Participants with symptomatic bradycardia - Administration of strong/potent cytochrome P3A4 (CYP3A4) inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib - Inability to swallow pills - Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of alectinib Atezolizumab - History of leptomeningeal disease - Uncontrolled tumor pain - Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). --- L858R ---