Colorectal cancer Head and Neck Squamous cell carcinoma Non Small cell lung Cancer renal cancer and melanoma (skin cancer)
Conditions
Interventions
See K2. Studydesign
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: * Signed Informed Consent Form * Age * 18 years * Able to comply with the study protocol, in the investigator*s judgment * Histologically or cytologically documented locally advanced or metastatic solid tumors meeting the following study drug-specific criteria * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 * Life expectancy * 12 weeks * Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) * Adequate hematologic and end organ function, defined by the following laboratory test results obtained within 14 days prior to the first study treatment: ANC * 1500 cells/µL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1) WBC counts > 2500 cells/µL Lymphocyte count * 250 cells/µL Serum albumin * 2.5 g/dL Platelet count * 100,000 cells/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1) Hemoglobin * 9.0 g/dL Patients may be transfused or receive erythropoietic treatment to meet this criterion. AST, ALT, and alkaline phosphatase * 2.5 × upper limit of normal (ULN), with the following exceptions: Patients with documented liver or bone metastases: alkaline phosphatase * 5 × ULN Serum bilirubin * 1.5 × ULN Patients with known Gilbert disease who have serum bilirubin level * 3 × ULN may be enrolled. INR and aPTT * 1.5 × ULN This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. Creatinine clearance * 30 mL/min Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration, or Modification of Diet in Renal Disease formulae may be used for creatinine clearance calculation. Note that 24-hour urine collection is not required. * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of 90 days after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 18 months after the last dose of obinutuzumab. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (* 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment p
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: Cancer-Specific Exclusions * NSCLC with sensitizing mutations in EGFR or ALK rearrangements * Melanoma with BRAF mutations * Active or untreated CNS metastases as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments; patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria: Measureable disease outside the CNS No metastases to midbrain, pons, or medulla No history of intracranial or spinal cord hemorrhage No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed No evidence of interim progression * 4 weeks between the completion of CNS-directed therapy and the screening radiographic study * 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 screening * Leptomeningeal disease * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX®) are allowed. * Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment. * Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to discontinue its use and receive a bisphosphonate instead while on study. * History of other malignancy within 2 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent, or other cancers with a similar outcome;General Medical Exclusions * Pregnant and lactating women * Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exceptions: Hormone-replacement therapy or oral contraceptives Tyrosine kinase inhibitors (TKIs) that have been discontinued > 7 days prior to Cycle 1, Day 1; baseline scans must be obtained after discontinuation of prior TKIs. * Investigational therapy within 28 days prior to initiation of study treatment * History of severe allergic, anaphylactic, or other hypersensitivity re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Outcome Measures The safety outcome measures for this study are as follows: * Nature and frequency of dose limiting toxicities (DLTs) * Nature, frequency, and severity of adverse events, per the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 * Changes in vital signs, physical findings, and clinical laboratory test results during and following atezolizumab administration * Incidence of anti-atezolizumab antibodies during the study relative to the incidence at baseline Efficacy Outcome Measures The efficacy outcome measures for this study are as follows: * Progression free survival (PFS), defined as the time from first study treatment to the first occurrence of disease progression or death, whichever occurs first * Objective response (PR plus CR), confirmed by repeat assessments * 4 weeks after initial documentation * Best overall response * Duration of objective response, defined as the time from the first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first * Overall survival, defined as the time from first study treatment to death from any cause Best overall response, objective response, and disease progression will be determined by investigator assessment using conventional RECIST v1.1 and immune modified RECIST criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Outcome Measures The PK outcome measures for the combination study are as follows: * Serum atezolizumab concentrations: Predose, maximum (Cmax), treatment discontinuation, and follow-up visit * 90 days after the last dose. * Serum ipilimumab concentrations: Predose, maximum (Cmax), treatment discontinuation, and follow-up visit * 90 days after the last dose. * Serum bevacizumab concentrations: Predose, maximum (Cmax), treatment discontinuation, and follow-up visit * 90 days after the last dose. * Serum obinutuzumab concentrations: Predose, maximum (Cmax), treatment discontinuation, and follow-up visit * 90 days after the last dose. Note: Assays may be generated at a later date to characterize the pharmacokinetics and immunogenicity of interferon alfa-2b and PEG-interferon alfa-2a. Exploratory Outcome Measures The exploratory outcome measures for this study are as follows: * Identification and profiling of exploratory biomarkers in plasma, serum, or blood (e.g., T-cell markers, interferon-gamma [IFN-*], and other markers) * Changes in immune-related markers (including but not limited to CD8, granzyme B, and other exploratory markers) in archival and fresh tumor tissue prior to and during combination atezolizumab treatment The following exploratory predictive biomarker endpoints will be assessed when appropriate: * PD-L1 status by immunohistochemistry or quantitative PCR in archival tissues and/or fresh biopsies * Status of other exploratory biomarkers related to PD-L1 or immune cell biology (including but not limited to CD8 or PD-1) and tumor biology (e.g., tumor mutation status) in archival tissues and/or fresh biopsies | — |
Countries
Netherlands
Outcome results
None listed