Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: A Study of the Safety and Tolerability of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors

Summary: This study will evaluate the safety, tolerability and pharmacokinetic variability of atezolizumab in combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU) (FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin.


Eligibility: Inclusion Criteria:
  General Inclusion criteria
  -  Measurable disease per RECIST v1.1
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Adequate hematologic and end organ function
  -  Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade less than or equal to (</=) 1 prior to study entry, with the exception of alopecia
  -  Ready to use reliable contraceptive procedures
  Inclusion Criteria Specific to HCC (Arm A and Arm D):
  -  Participants with advanced or metastatic and/or unresectable HCC
  -  The participant has disease that is not amenable to a curative approach
  -  No prior line of systemic therapy (includes participants who are sorafenib-naïve)
  -  Willing to undergo fresh liver biopsy if provided archival tissue was taken greater than (>) 6 months from Cycle 1 Day 1
  -  Child-Pugh Score of up to B7
  -  Serum bilirubin </= 3 times upper limit of normal (x ULN)
  -  International normalized ratio (INR) and activated partial thromboplastin time (aPTT) </= 2 x ULN
  -  Albumin >2.8 grams per deciliter (g/dL)
  -  Documented virology status of hepatitis, as confirmed by screening hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and/or anti-hepatitis C virus (anti-HCV)
  -  Antiviral therapy per local standard-of-care if active hepatitis B virus (HBV)
  Inclusion Criteria Specific to Gastric Cancer (Arm B)
  -  Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or GEJ in participants who have not received prior systemic therapy for metastatic disease
  -  Absence of HER2 expression documented as in situ hybridization (ISH) negative on previously collected and assessed tumor tissue upon initial diagnosis of disease
  Inclusion criteria specific to metastatic pancreatic cancer (Arm C)
  -  Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas
  -  No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease
  Inclusion Criteria Specific to mEC (Arm E)
  -  Histologically or cytologically confirmed locally mEC or metastatic adenocarcinoma of the GEJ Siewert Classification Type I in participants who have not received prior systemic therapy for primary and metastatic disease or chemoradiation therapy for primary disease
  -  Absence of HER2 expression documented as ISH-negative on previously collected and assessed tumor tissue upon initial diagnosis of disease
  -  Willing to undergo biopsy if archival tissue is not available or if archival tissue was taken >6 months from Cycle 1 Day 1
  Exclusion Criteria:
  General Exclusion Criteria
  -  Uncontrolled pleural effusion, pericardial effusion, or ascites
  -  Uncontrolled tumor-related pain
  -  Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
  -  Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease (exception for participants in Arm A and Arm D)
  -  Known primary central nervous system (CNS) malignancy or untreated or active CNS metastases
  -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or other recombinant human antibodies
  -  Positive test for Human Immunodeficiency Virus (HIV)
  -  Active hepatitis B (chronic or acute), or hepatitis C (exception for participants in Arm A and Arm D)
  -  Active tuberculosis
  -  Severe infections within 4 weeks prior to Day 1
  -  Signs or symptoms of significant infection within 2 weeks prior to Day 1
  -  Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
  -  Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to Day 1, unstable arrhythmias, or unstable angina
  -  History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to Day 1
  -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  -  Any serious medical condition or abnormality in clinical laboratory tests that, in the investigators judgment, precludes the participants safe participation in and completion of the study
  -  Malignancies other than pancreatic carcinoma within 2 years prior to study start, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS >90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
  Exclusion Criteria Related to Medications
  -  Prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1) therapeutic antibody
  -  Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is longer, prior to screening
  -  Treatment with systemic corticosteroids or other immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1
  -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  -  Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  -  Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-FU, nab-paclitaxel (or other taxanes) or gemcitabine
  Bevacizumab and Vanucizumab-Specific Exclusions (Arms A, B, and D)
  -  Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab or vanucizumab
  -  History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to Day 1
  -  History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction within 6 months prior to Day 1 of Cycle 1
  -  Clinical signs or symptoms of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  -  Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
  -  Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  -  Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection
  -  Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses of large volume. HCC participants (Arm A and D) with vascular invasion of the portal or hepatic veins may be enrolled
  -  History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1
  -  Radiotherapy within 28 days and abdominal/pelvic radiotherapy within 60 days prior to Day 1 of Cycle 1
  -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1
  -  Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID)
  Exclusions specific to Arms A and D (HCC)
  -  Participants with untreated or incompletely treated varices with bleeding or high-risk for bleeding
  -  Treatment with any HCV anti-viral therapy within 4 weeks prior to Cycle 1 Day 1
  -  Moderate or severe ascites
  -  Hepatic encephalopathy
  Exclusions Specific to Arm E (Metastatic Esophageal Cancer)
  -  HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry
  -  Prior chemotherapy treatment, including radio-sensitization in pre- and post-operative settings

Relevance to patient case: not relevant