Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Atezolizumab Combined With Intratumoral G100 AnD Immunogenic Radiotherapy in Patients With Advanced Solid Tumors (AGADIR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03915678
Recruitment Status : Not yet recruiting
First Posted : April 16, 2019
Last Update Posted : April 16, 2019
Sponsor:
Collaborators:
Roche Pharma AG
National Cancer Institute, France
Immune Design
Information provided by (Responsible Party):
Institut Bergonié

Brief Summary:
Basket trial concept to independently and simultaneously assess the effects of the association of atezolizumab + G100 + radiotherapy in multiple solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Pancreatic Cancer Virus-associated Tumors Non Small Cell Lung Cancer Melanoma Bladder Cancer Triple Negative Breast Cancer Drug: Association atezolizumab + G100 + RT Phase 2

Detailed Description:

6 independent, multicenter, prospective, single-arm phase II trials, based on 2-stage Simon's optimal design, will be conducted in parallel to assess the efficacy of atezolimab + G100 + radiotherapy, separately, in distinct populations of solid tumors:

  • Population 1: pancreatic cancer
  • Population 2: virus-associated tumors
  • Population 3: non-small lung cancer
  • Population 4: melanoma cancer
  • Population 5: bladder cancer
  • Population 6: triple negative breast cancer

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 247 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

6 independent single-arm, multicenter, phase II trials, based on 2-stage Simon's optimal design (Simon R, Controlled Clinical Trials 1989):

  • Population 1: pancreatic cancer
  • Population 2: virus-associated tumors
  • Population 3: non-small lung cancer
  • Population 4: melanoma cancer
  • Population 5: bladder cancer
  • Population 6: triple negative breast cancer
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Atezolizumab Combined With Intratumoral G100 AnD Immunogenic Radiotherapy in Patients With Advanced Solid Tumors
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Population 1: Pancreatic cancer
Participants with pancreatic cancer will be treated with Atezolizumab combined with intratumoral G100 and radiotherapy.
Drug: Association atezolizumab + G100 + RT

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

G100 will be administered by intra-tumoral at fixed dose (20µg), once weekly for at least 6 weeks and for a maximum of 12 weeks. Treatment by G100 will start one week before atezolizumab administration (e.g, Day -7, "impregnation phase"). Note that a maximum of 3 lesions can be injected.

Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration:

  • Short course irradiation on injected metastasis: 2 fractions of 2 Gy for a total dose of 4 Gy,
  • High dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Experimental: Population 2: Virus-associated tumors
Participants with virus-associated tumors will be treated with Atezolizumab combined with intratumoral G100 and radiotherapy.
Drug: Association atezolizumab + G100 + RT

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

G100 will be administered by intra-tumoral at fixed dose (20µg), once weekly for at least 6 weeks and for a maximum of 12 weeks. Treatment by G100 will start one week before atezolizumab administration (e.g, Day -7, "impregnation phase"). Note that a maximum of 3 lesions can be injected.

Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration:

  • Short course irradiation on injected metastasis: 2 fractions of 2 Gy for a total dose of 4 Gy,
  • High dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Experimental: Population 3: Non-small lung cancer
Participants with non-small lung cancer will be treated with Atezolizumab combined with intratumoral G100 and radiotherapy.
Drug: Association atezolizumab + G100 + RT

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

G100 will be administered by intra-tumoral at fixed dose (20µg), once weekly for at least 6 weeks and for a maximum of 12 weeks. Treatment by G100 will start one week before atezolizumab administration (e.g, Day -7, "impregnation phase"). Note that a maximum of 3 lesions can be injected.

Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration:

  • Short course irradiation on injected metastasis: 2 fractions of 2 Gy for a total dose of 4 Gy,
  • High dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Experimental: Population 4: Melanoma
Participants with melanoma will be treated with Atezolizumab combined with intratumoral G100 and radiotherapy.
Drug: Association atezolizumab + G100 + RT

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

G100 will be administered by intra-tumoral at fixed dose (20µg), once weekly for at least 6 weeks and for a maximum of 12 weeks. Treatment by G100 will start one week before atezolizumab administration (e.g, Day -7, "impregnation phase"). Note that a maximum of 3 lesions can be injected.

Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration:

  • Short course irradiation on injected metastasis: 2 fractions of 2 Gy for a total dose of 4 Gy,
  • High dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Experimental: Population 5: Bladder cancer
Participants with bladder cancer will be treated with Atezolizumab combined with intratumoral G100 and radiotherapy.
Drug: Association atezolizumab + G100 + RT

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

G100 will be administered by intra-tumoral at fixed dose (20µg), once weekly for at least 6 weeks and for a maximum of 12 weeks. Treatment by G100 will start one week before atezolizumab administration (e.g, Day -7, "impregnation phase"). Note that a maximum of 3 lesions can be injected.

Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration:

  • Short course irradiation on injected metastasis: 2 fractions of 2 Gy for a total dose of 4 Gy,
  • High dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Experimental: Population 6: Triple negative breast cancer
Participants with triple negative breast cancer will be treated with Atezolizumab combined with intratumoral G100 and radiotherapy.
Drug: Association atezolizumab + G100 + RT

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

G100 will be administered by intra-tumoral at fixed dose (20µg), once weekly for at least 6 weeks and for a maximum of 12 weeks. Treatment by G100 will start one week before atezolizumab administration (e.g, Day -7, "impregnation phase"). Note that a maximum of 3 lesions can be injected.

Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration:

  • Short course irradiation on injected metastasis: 2 fractions of 2 Gy for a total dose of 4 Gy,
  • High dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.




Primary Outcome Measures :
  1. Assessment of the antitumor activity of atezolizumab combined with G100 and radiotherapy (independently for each population). [ Time Frame: Within 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of objective response rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR) or partial response (PR) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.


Secondary Outcome Measures :
  1. 6-month objective response (OR) independently for each population. [ Time Frame: 6 months ]
    Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed at 6 months, based on RECIST 1.1 criteria.

  2. 6-month Progression-free rate (PFR), independently for each population. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.

  3. Best overall response, independently for each population. [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Best overall response is defined as the best response across all time points (RECIST 1.1). The best overall response is determined once all the data for the patient is known (RECIST 1.1).

  4. 1-year progression-free survival, independently for each population. [ Time Frame: 1 year ]
    Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.

  5. 2-year progression-free survival, independently for each population. [ Time Frame: 2 years ]
    Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.

  6. 1-year overall survival, independently for each population. [ Time Frame: 1 year ]
    Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).

  7. 2-year overall survival, independently for each population. [ Time Frame: 2 years ]
    Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).

  8. Safety profile, independently for each population: Common Terminology Criteria for Adverse Events version 5 [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.

  9. Tumor immune cells levels [ Time Frame: before treatment onset and cycle 3 day 1 (each cycle is 21 days) ]
    Levels of immune cells in tumor will be measured by immunohistochemistry.

  10. Blood cytokines levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of cytokines in blood will be measured by ELISA.

  11. Blood lymphocytes levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of lymphocytes in blood will be measured by flow cytometry.

  12. Blood kynurenine levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of kynurenine in blood will be measured by ELISA.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histology: histologically confirmed pancreatic cancer (population 1), virus-associated tumors tumors (population 2), non-small lung cancer (population 3), melanoma (population 4), bladder cancer (population 5), triple negative breast cancer (population 6). For population 2, diagnosis must be confirmed by the RRePS Network as recommended by the French NCI,
  2. Metastatic disease with at least one injectable lesion. Note that lesion must be a lymph node, or cutaneous, subcutaneous, intramuscular, liver metastasis,
  3. Age ≥ 18 years,
  4. ECOG, Performance status ≤ 1,
  5. At least three lesions: one injectable lesion (G100), one lesion that can be treated by radiotherapy and one site of disease that must be uni-dimensionally ≥ 10 mm considered as measurable according to RECIST (outside any previously irradiated field, except if progressive as per RECIST at inclusion). This lesion will not be treated by radiotherapy and G100. However, note that lesion(s) that will be treated by radiotherapy and G100 will also be considered as measurable,
  6. Life expectancy > 6 months,
  7. At least one tumor site that can be biopsied for research purpose,
  8. Availability of archived paraffin-embedded tumor tissue for research purpose,
  9. Participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
  10. Adequate hematological, renal, metabolic and hepatic functions:

    1. Hemoglobin ≥ 9 g/dl (participants may have received prior red blood cell [RBC] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.5 G/l, platelet count ≥ 100 G/l, white blood cell count ≥ 2.5 G/l (or within local laboratory normal limits) and lymphocyte count ≥ 0.75 G/l
    2. Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (ASP) ≤ 2.5 x upper limit of normality (ULN) (≤ 5 in case of extensive skeletal involvement for AP exclusively and ≤ 5 x ULN in case of liver metastasis for AST and ALT).
    3. Direct bilirubin ≤ 1.5 x ULN,
    4. Albumin ≥ 25g/l.
    5. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 30 ml/min (according to Cockroft and Gault formula).
    6. INR ≤ 1.5 x ULN
    7. aPTT ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
    8. Serum calcium within normal laboratory ranges,
    9. Thyroid function within normal laboratory ranges (TSH, free T3, free T4)
  11. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
  12. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
  13. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE, version 5.0)),
  14. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion. Note that serum pregnancy test must be repeated 72 hours prior to receiving the first dose of study medication,
  15. Both women and men must agree to use an effective method of contraception throughout the treatment period and for five months after discontinuation of treatment. Acceptable methods for contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier. Subjects of childbearing potential are those who have not been surgically sterilized (e.g., vasectomy for males and hysterectomy for females) or have not been free from menses for ≥ 1 year.
  16. Voluntary signed and dated written informed consents prior to any specific study procedure,
  17. Participants with a social security in compliance with the French law.

Exclusion Criteria:

  1. Previous treatment with atezolizumab or TLS agonist
  2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2,
  3. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
  4. Women who are pregnant or breast feeding,
  5. Participation to a study involving a medical or therapeutic intervention in the last 30 days,
  6. Previous enrolment in the present study,
  7. Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
  8. Known hypersensitivity to CHO cell products or to any involved study drug or of its formulation components,
  9. History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
  10. Treatment with systemic immunosuppressive medications including, but not limited, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to inclusion. Participants who have received acute and/or low-dose systemic immunosuppressant medications (e.g. a one-time dose of dexamethasone for nausea or chronic use of ≤10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion and approval by the Sponsor.
  11. The use of inhaled corticosteroids and mineral corticoids is allowed.
  12. Major surgical procedure, open biopsy or significant traumatic injury within 28 days before inclusion,
  13. Any of the following cardiac criteria:

    • Congestive heart failure ≥ New York Heart Association (NHYA) class 2,
    • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
    • Myocardial infarction less than 6 months before inclusion
    • Uncontrolled cardiac arrhythmias,
    • Known left ventricular ejection fraction (LVEF) <50%
  14. Individuals deprived of liberty or placed under legal guardianship,
  15. Prior organ transplantation, including allogeneic stem cell transplantation,
  16. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver and inherited liver disease, ,
  17. History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease or colitis.
  18. History of autoimmune disease including, but not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, systemic immune activation, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barré syndrome, Bell's palsy.

    • Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible,
    • Participants with controlled Type I diabetes mellitus on a stable insulin regimen are eligible,
    • Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with only dermatologic manifestations <10% of the skin (e.g, participants with psoriatic arthritis would be excluded) are eligible.
  19. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  20. Poorly controlled Type II diabetes mellitus defined as a screening fasting plasma glucose ≥160 mg/dL (or 8.8 mmol/L).
  21. Severe infections within 2 weeks prior to inclusion, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  22. Received therapeutic oral or IV antibiotics within 2 weeks prior to inclusion. Participants receiving prophylactic antibiotics (e.g, for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  23. Participants with oral anticoagulation therapy of the potential of bleeding. For ASA and anti-platelet agents, we follow the recommendations for injection from consensus guidelines. Based on the consensus guidelines from the Cardiovascular and Interventional Radiology Society of Europe, if a patient is to have a superficial lymph node or subcutaneous mass injected, NSAIDs, aspirin, or clopidogrel may be used and do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Sponsor and may need to be discontinued before beginning G100 therapy. (Higher risk would include deeper lesions or those within organs or with the potential for bleeding without the possibility of simple compression to help stop the bleeding).
  24. Participant has spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >2 weeks prior to inclusion.
  25. Administration of a live, attenuated vaccine within 4 weeks before the start of study medication or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (approximatively October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to the start of study medication or at any time during the study or within 5 months after the last dose of atezoluzumab.
  26. Has known active hepatitis B or hepatitis C,
  27. Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS),
  28. Has a known history of tuberculosis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03915678


Contacts
Layout table for location contacts
Contact: Antoine ITALIANO, MD, PhD +33 5.56.33.33.33 a.italiano@bordeaux.unicancer.fr
Contact: Simone MATHOULIN-PELISSIER, MD, PhD s.mathoulin@bordeaux.unicancer.fr

Locations
Layout table for location information
France
Institut Bergonié Not yet recruiting
Bordeaux, France, 33076
Contact: Antoine ITALIANO, MD, PhD       a.italiano@bordeaux.unicancer.fr   
Centre Georges François Leclerc Not yet recruiting
Dijon, France, 21079
Contact: Nicolas ISAMBERT, MD         
Principal Investigator: Nicolas ISAMBERT, MD         
Centre Oscar Lambret Not yet recruiting
Lille Cedex, France, 59020
Contact: Nicolas PENEL, MD, PhD         
Principal Investigator: Nicolas PENEL, MD, PhD         
Centre Léon Bérard Not yet recruiting
Lyon Cedex 08, France, 69373
Contact: Philippe CASSIER, MD         
Principal Investigator: Philippe CASSIER, MD         
Institut Paoli Calmettes Not yet recruiting
Marseille, France, 13273
Contact: Anthony GONCALVES, MD, PhD         
Principal Investigator: Anthony GONCALVES, MD, PhD         
Institut du Cancer de Montpellier Not yet recruiting
Montpellier, France, 34298
Contact: Diego TOSI, MD         
Principal Investigator: Diego TOSI, MD         
Institut Curie Not yet recruiting
Paris, France, 75005
Contact: Christophe LE TOURNEAU, MD         
Principal Investigator: Christophe LE TOURNEAU, MD         
Institut de Cancérologie de l'Ouest - Site René Gauducheau Not yet recruiting
Saint-Herblain, France, 44805
Contact: Steven LE GOUILLL, MD         
Principal Investigator: Steven LE GOUILLL, MD         
IUCT Oncopôle Not yet recruiting
Toulouse, France, 31052
Contact: Jean-Pierre DELORD, MD, PhD         
Principal Investigator: Jean-Pierre DELORD, MD, PhD         
Institut Gustave Roussy Not yet recruiting
Villejuif Cedex, France, 94805
Contact: Christophe MASSARD, MD, PhD         
Principal Investigator: Christophe MASSARD, MD, PhD         
Sponsors and Collaborators
Institut Bergonié
Roche Pharma AG
National Cancer Institute, France
Immune Design

Layout table for additonal information
Responsible Party: Institut Bergonié
ClinicalTrials.gov Identifier: NCT03915678     History of Changes
Other Study ID Numbers: IB 2019-01
2019-000850-78 ( EudraCT Number )
First Posted: April 16, 2019    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut Bergonié:
Immunotherapy
Radiotherapy
Oncology
Metastatic

Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Urinary Bladder Neoplasms
Triple Negative Breast Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs