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

Roche

Status and phase: Completed; Phase 1

Conditions: Solid Cancers

Treatments: Drug: Ipilimumab; Drug: Atezolizumab; Drug: Obinutuzumab; Drug: PEG-interferon alfa-2a; Drug: Bevacizumab; Drug: Interferon alfa-2b

Study type: Interventional

Funder types: Industry

Identifiers

NCT02174172

2014-000812-33 (EudraCT Number)

GO29322

Details and patient eligibility

About

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).

Enrollment: 158 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Inclusion criteria specific to Arm A: Atezolizumab+ Ipilimumab

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

Inclusion criteria specific to Arm B: Atezolizumab+ Interferon alfa-2b

• 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)

Inclusion Criteria Specific to Arm C (Atezolizumab plus PEG-Interferon Alafa-2a):

• Cohort 1: participants with RCC

Inclusion Criteria Specific to Arm D (Atezolizumab plus PEG-Interferon Alfa-2a +Bevacizumab)

• 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

Inclusion Criteria Specific to Arm E (Atezolizumab +Obinutuzumab)

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

Inclusion Criteria Specific to prior Anti-PD-L1/PD-1 Treated Cohorts:

• 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

Exclusion Criteria Related to Medications:

• 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)

Exclusion Criteria Specific to Interferon Alpha Therapy (Arms B-D):

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

Exclusion Criteria Specific to Bevacizumab (Arm D)

• 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

Exclusion Criteria Specific Obinutuzumab (Arm E)

• Hypersensitivity to obinutuzumab
• Prior treatment with obinutuzumab

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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158 participants in 5 patient groups

Arm A: Atezolizumab with Ipilimumab

Experimental group

Description:

Participants will receive atezolizumab along with ipilimumab.

Treatment:

Drug: Ipilimumab

Drug: Atezolizumab

Arm B: Atezolizumab with Interferon alfa-2b

Experimental group

Description:

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

Treatment:

Drug: Interferon alfa-2b

Drug: Atezolizumab

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

Experimental group

Description:

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

Treatment:

Drug: PEG-interferon alfa-2a

Drug: Atezolizumab

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

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: PEG-interferon alfa-2a

Drug: Atezolizumab

Arm E: Atezolizumab with Obinutuzumab

Experimental group

Description:

Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone.

Treatment:

Drug: Obinutuzumab

Drug: Atezolizumab