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My Pathway: An open-label phase IIa study evaluating trastuzumab/pertuzumab, erlotinib, vemurafenib/cobimetinib, vismodegib, alectinib, and atezolizumab in patients who have advanced solid tumors with mutations or gene expression abnormalities predictive of response to one of these agents

Description

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.

Many cancers contain molecular abnormalities (cells show biological and genetic changes in the laboratory) that cause or contribute to their ability to grow and spread. By blocking the effects of these abnormalities, the growth of cancer may be stopped or slowed down. Many new cancer drugs work in this way. Because they block the effects of specific molecular abnormalities within the cancer, they are known as “targeted” agents.

As more such targets are identified, and more drugs are found to work against them, more patients are now having molecular tests done on their tumor tissue (“molecular profiling”), in order to identify potential molecular targets for treatment.

Participants' voluntary participation in this research study may help find out what effects, good or bad, that Herceptin®/Perjeta®, Tarceva®, Zelboraf®/Cotellic®, Erivedge®, Alecensa® and Tecentriq® may have in participants with the same type of cancer.

Status

Accepting new patients

Primary Study Objective(s)

  • Percentage of participants with overall response
  • Tumor response, assessed using Response Evaluation Criteria in Solid Tumors (RECIST) for all arms except atezolizumab (atezolizumab arm assessed using immune-modified RECIST)

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients with:

  • Life expectancy greater than or equal to (>/=) 12 weeks
  • Histologically documented metastatic cancer (solid tumors, not including hematologic malignancies)
  • History of receiving 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 or evaluable disease by RECIST v1.1

Additional 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 over-expression, amplification or HER2-activating mutation
    • For participants screened using a blood assay, obtain tissue-based testing result confirming study eligibility (within first four weeks after enrollment)
  • Participants with breast, gastric or gastroesophageal junction cancer must have HER2-activating mutation.
  • Left ventricular ejection fraction 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 may be submitted within four weeks after enrollment

Erlotinib

  • Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating 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])
    • For participants screened using a blood assay, obtain tissue-based testing result confirming study eligibility (within first four weeks after enrollment).

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 programmed death-ligand 1 (PD-L1) copy number gain/amplification, deficiency in mismatch repair enzymes (dMMR), high levels of micro-satellite instability (MSI-H), high tumor mutational burden (TMB-H), alterations of deoxyribonucleic acid (DNA) proofreading/repair genes (example., polymerase epsilon [POLE], polymerase delta 1 [POLD1])
  • 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 may be submitted within four weeks after enrollment.

Excluding patients with these conditions:

  • 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)

Additional study drug-specific exclusion criteria:

Trastuzumab plus pertuzumab

  • Breast, gastric, or gastroesophageal junction cancer identified by HER2 amplification or over-expression
  • 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
  • Epidermal growth factor receptor (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 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 millimeters 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 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

  • Metastatic NSCLC, metastatic urothelial carcinoma or microsatellite instability high metastatic colorectal cancer
  • Previous treatment with atezolizumab or another programmed death-1 (PD-1)/PD-L1 inhibitor
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells
  • Known allergy or hypersensitivity to any component of the atezolizumab formulation
  • Active or history of autoimmune disease or immune deficiency
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan