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

NCT02174172 | Completed Phase 1

• 2 other identifiers: GO293222014-000812-33
• Study Type: interventional
• Target: 158
• Locations: 2 countries
• Sites: 9

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

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose (RP2D) of Atezolizumab When Given in Combination With Ipilimumab and Interferon Alfa-2b

  From the first atezolizumab treatment up to 21 days

• Percentage of Participants with Adverse Events

  From the first atezolizumab treatment up to 4.5 years (yr)

Secondary Outcomes (15)

• Percentage of Participants with Best Overall Response, as Assessed Using Conventional Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])

• Percentage of Participants with Best Overall Response, as Assessed Using Immune Modified RECIST Criteria

  Screening to progression or death, up to 4.5 years (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])

• Duration of Objective Response

  Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])

• Overall Survival

  Baseline to death (up to 4.5 yr)

• Progression-Free Survival

  Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])

Study Arms (5)

Arm A: Atezolizumab with Ipilimumab

EXPERIMENTAL

Participants will receive atezolizumab along with ipilimumab.

Drug: Atezolizumab; Drug: Ipilimumab

Arm B: Atezolizumab with Interferon alfa-2b

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Interferon alfa-2b

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

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: PEG-interferon alfa-2a

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

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Bevacizumab; Drug: PEG-interferon alfa-2a

Arm E: Atezolizumab with Obinutuzumab

EXPERIMENTAL

Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone.

Drug: Atezolizumab; Drug: Obinutuzumab

Interventions

Atezolizumab DRUG

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

Also known as: Tecentriq, RO5541267, MPDL3280A

Arm A: Atezolizumab with Ipilimumab; Arm B: Atezolizumab with Interferon alfa-2b; Arm C: Atezolizumab with PEG- interferon alfa-2a; Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab; Arm E: Atezolizumab with Obinutuzumab

Bevacizumab DRUG

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

Also known as: Avastin®

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

Interferon alfa-2b 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 B: Atezolizumab with Interferon alfa-2b

Ipilimumab 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 A: Atezolizumab with Ipilimumab

Obinutuzumab 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).

Arm E: Atezolizumab with Obinutuzumab

PEG-interferon alfa-2a DRUG

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

Also known as: Pegasys®

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Active or untreated central nervous system (CNS) metastases, as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, 85258, United States

Location

Mayo Clinic- Scottsdale

Scottsdale, Arizona, 85259, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232-7610, United States

Location

The Netherlands Cancer Institute of Amsterdam

Amsterdam, 1066 CX, Netherlands

Location

MeSH Terms

Interventions

atezolizumab; Bevacizumab; Interferon alpha-2; Ipilimumab; obinutuzumab; peginterferon alfa-2a

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: June 25, 2014
• Study Start: August 18, 2014
• Primary Completion: November 25, 2019
• Study Completion: November 25, 2019
• Last Updated: May 12, 2020

Record last verified: 2020-05

Locations

US (8); NL (1)