A Study to Assess the Safety and Tolerability of Atezolizumab in Combination With Other Immune-Modulating Therapies in Participants With Locally Advanced or Metastatic Solid Tumors

NCT ID: NCT02174172

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-18
• Study Completion Date: 2019-11-25

Brief Summary

This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG-interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).

Conditions

Solid Cancers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Atezolizumab with Ipilimumab

Participants will receive atezolizumab along with ipilimumab.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.

Ipilimumab

Intervention Type: DRUG

Participants will receive Ipilimumab 1, or 3 mg/kg IV, single dose, or multiple-dose regimen q3w for up to 4 cycles (Cycle = 21 days).

Arm B: Atezolizumab with Interferon alfa-2b

Participants will receive atezolizumab along with Interferon alfa-2b.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.

Interferon alfa-2b

Intervention Type: DRUG

Participants will receive Interferon alfa-2b 3, 5, or 10 million international units subcutaneously every other day for up to 3 doses per week.

Arm C: Atezolizumab with PEG- interferon alfa-2a

Participants will receive atezolizumab along with PEG- interferon alfa-2a.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.

PEG-interferon alfa-2a

Intervention Type: DRUG

Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles (Cycle = 21 days).

Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab

Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.

Bevacizumab

Intervention Type: DRUG

Participant will receive Bevacizumab 15 milligrams per kilograms (mg/kg) IV infusion q3w.

PEG-interferon alfa-2a

Intervention Type: DRUG

Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles (Cycle = 21 days).

Arm E: Atezolizumab with Obinutuzumab

Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab 1000 milligrams will be administered as pre-treatment on 2 consecutive days (Day -13 and Day -12) prior to treatment start with atezolizumab on Cycle 1, Day 1 (cycle length=21 days). An additional two doses of obinutuzumab will be administered on Days 85 and 86 of study treatment (Cycle 5, Day 1 and Cycle 5, Day 2).

Interventions

Atezolizumab

Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.

Intervention Type: DRUG

Bevacizumab

Participant will receive Bevacizumab 15 milligrams per kilograms (mg/kg) IV infusion q3w.

Intervention Type: DRUG

Interferon alfa-2b

Participants will receive Interferon alfa-2b 3, 5, or 10 million international units subcutaneously every other day for up to 3 doses per week.

Intervention Type: DRUG

Ipilimumab

Participants will receive Ipilimumab 1, or 3 mg/kg IV, single dose, or multiple-dose regimen q3w for up to 4 cycles (Cycle = 21 days).

Intervention Type: DRUG

Obinutuzumab

Obinutuzumab 1000 milligrams will be administered as pre-treatment on 2 consecutive days (Day -13 and Day -12) prior to treatment start with atezolizumab on Cycle 1, Day 1 (cycle length=21 days). An additional two doses of obinutuzumab will be administered on Days 85 and 86 of study treatment (Cycle 5, Day 1 and Cycle 5, Day 2).

Intervention Type: DRUG

PEG-interferon alfa-2a

Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles (Cycle = 21 days).

Intervention Type: DRUG

Other Intervention Names

Tecentriq, RO5541267, MPDL3280A; Avastin®; Pegasys®

Eligibility Criteria

Inclusion Criteria

• 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 greater than or equal to (>/=) 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function as confirmed by laboratory results within 14 days prior to the first study treatment

• Escalation stage: NSCLC participants
• Mandatory biopsy cohort: NSCLC or melanoma atezolizumab
• Prior atezolizumab-treated cohort: participants with NSCLC or melanoma previously treated with atezolizumab

• Escalation stage: RCC or melanoma participants
• Expansion stage: RCC or melanoma participants
• Mandatory biopsy cohort: RCC or melanoma participants
• Prior immunotherapy-treated cohort: participants with RCC, NSCLC, or melanoma previously treated with programmed death-ligand 1 (PD-L1)/ Programmed death 1 (PD-1)

• Cohort 1: participants with RCC

• Cohort 1: participants with metastatic RCC with no prior line of systemic therapy for metastatic disease
• Cohorts 2-3: disease progression during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic non-squamous solid tumors; participants with sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements must have failed or are intolerant to prior treatment with EGFR or ALK inhibitors; participants with melanoma with actionable BRAF mutations (e.g., V600) must have failed or are intolerant to prior treatment with BRAF inhibitors

• R/M HNSCC participants with at least one prior line of systemic therapy

• No permanent discontinuation of atezolizumab or other immunotherapies due to a treatment-related adverse event
• Recovery from all immunotherapy-related adverse events to Grade less than or equal to (≤) 1 or baseline at the time of consent

Exclusion Criteria

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 exception: (1) hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors (TKIs) that have been discontinued greater than (>) 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 reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation
• History of or active autoimmune disease
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation
• History of human immunodeficiency virus (HIV)
• Participants with active hepatitis B
• Participants with active hepatitis C
• Participants with active tuberculosis
• Participants with a history of confirmed progressive multifocal leukoencephalopathy
• Any serious medical condition, physical examination finding, or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study

Cancer-Specific Exclusions:

• Active or untreated central nervous system (CNS) metastases, as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• 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); participants with indwelling catheters are allowed.
• Uncontrolled tumor-related pain
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• 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

• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies (Note: Participants enrolled in the prior anti-PD-L1/PD-1 treated cohorts with melanoma may have received prior anti-cytotoxic T-lymphocyte-associated protein 4 treatment or other immunotherapies)
• Treatment with systemic immunostimulatory agents within four weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
• Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1 (the use of inhaled corticosteroids and mineralocorticoids is allowed)

• History of depression, suicidal ideation or behavior, bipolar disorder, or psychosis
• Hypersensitivity to interferon alpha or any component of the product

• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease within 6 months prior to Day 1
• History of hemoptysis
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• History of tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
• Clinical signs or symptoms of gastrointestinal 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
• Proteinuria, as demonstrated by urine dipstick or > 1.0 gram 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

• Hypersensitivity to obinutuzumab
• Prior treatment with obinutuzumab

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, United States

Mayo Clinic- Scottsdale

Scottsdale, Arizona, United States

UCLA

Los Angeles, California, United States

Yale University

New Haven, Connecticut, United States

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Sarah Cannon Research Inst.

Nashville, Tennessee, United States

Vanderbilt Medical Center

Nashville, Tennessee, United States

The Netherlands Cancer Institute of Amsterdam

Amsterdam, , Netherlands

Countries

United States; Netherlands

Other Identifiers

2014-000812-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29322

Identifier Type: -

Identifier Source: org_study_id