Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

A Phase 1b Study of Atezolizumab in Combination With Erlotinib or Alectinib in Participants With Non-Small Cell Lung Cancer (NSCLC)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02013219
Recruitment Status : Active, not recruiting
First Posted : December 17, 2013
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE December 11, 2013
First Posted Date  ICMJE December 17, 2013
Last Update Posted Date November 14, 2019
Actual Study Start Date  ICMJE April 3, 2014
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2017)
  • Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: 28 days ]
  • Recommended Phase II Dose (RP2D) of Atezolizumab and Erlotinib [ Time Frame: 28 days ]
  • Recommended RP2D of Atezolizumab and Alectinib [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2013)
Incidence of dose-limiting toxicities [ Time Frame: Day 8, Cycle 1 until Day 1, Cycle 2 (21 days from start of MPDL3280A treatment) ]
Change History Complete list of historical versions of study NCT02013219 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2018)
  • Minimum Plasma Concentration (Cmin) of Alectinib and Major Metabolites, as Appropriate [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycles 1−4, Day 8 of Cycle 1 (Cycle 1 =28 days; Cycle 2 onwards=21 days) ]
  • Progression-Free Survival (PFS) as Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: First dose of study treatment up to disease progression or death from any cause (up to approximately 6 years) ]
  • Overall Survival [ Time Frame: First dose of study treatment up to death from any cause during the study (up to approximately 6 years) ]
  • Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR]) Using RECIST [ Time Frame: Baseline up to disease progression or death from any cause (up to approximately 6 years) ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 6 years ]
  • Percentage of Participants with Anti-Drug Antibodies (ADAs) Against Atezolizumab [ Time Frame: Baseline up to approximately 6 years ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Day 1 of Cycles 1−4, Day 8 of Cycle 1 (Cycle 1 =21 days; Cycle 2 onwards=28 days) ]
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 and at study termination (up to approximately 5 years; Cycle 1=21 days; Cycle 2 onwards=28 days) ]
  • Maximum Plasma Concentration (Cmax) of Erlotinib [ Time Frame: Day 1 of Cycles 1−4, Day 8 of Cycle 1 (Cycle 1 =21 days; Cycle 2 onwards=28 days) ]
  • Minimum Plasma Concentration (Cmin) of Erlotinib [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycles 1−4, Day 8 of Cycle 1 (Cycle 1 =21 days; Cycle 2 onwards=28 days) ]
  • Maximum Plasma Concentration (Cmax) of Alectinib and Major Metabolites, as Appropriate [ Time Frame: Day 1 of Cycles 1−4, Day 8 of Cycle 1 (Cycle 1 =21 days; Cycle 2 onwards=28 days) ]
  • Duration of Objective Response as Assessed Using RECIST [ Time Frame: First occurrence of a documented objective response up to disease progression or death from any cause (up to approximately 6 years) ]
  • Percentage of Participants with Best Overall Response [ Time Frame: Baseline up to disease progression or death from any cause (up to approximately 6 years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2013)
  • Incidence of adverse events [ Time Frame: Up to 12 months ]
  • Incidence of anti-therapeutic antibodies against MPDL3280A [ Time Frame: Up to 6 months ]
  • Maximum serum concentration (Cmax) of MPDL3280A [ Time Frame: On Day 8 ]
  • Maximum plasma concentration (Cmax) of Tarceva [ Time Frame: Up to 3 months ]
  • Progression-Free Survival [ Time Frame: Up to 15 months ]
  • Overall Survival [ Time Frame: Up to 15 months ]
  • Overall Response, as Determined by the Investigator with RECIST v1.1 [ Time Frame: Up to 15 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1b Study of Atezolizumab in Combination With Erlotinib or Alectinib in Participants With Non-Small Cell Lung Cancer (NSCLC)
Official Title  ICMJE A Phase 1b Study of the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered With Erlotinib or Alectinib in Patients With Advanced Non-Small Cell Lung Cancer
Brief Summary

This open-label, multicenter study will assess the safety, tolerability, and pharmacokinetics of intravenous (IV) dosing of atezolizumab in combination with oral erlotinib or alectinib in participants with NSCLC.

This study has two stages. In the erlotinib group, the combination treatment will be given to participants with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treatment-naive, advanced (nonresectable) NSCLC in a safety-evaluation stage and to participants with previously untreated EGFR mutation-positive, advanced NSCLC in an expansion stage (Stage 2). In the alectinib group, for both the safety-evaluation and expansion stages (Stages 1 and 2), the combination will be given to participants who are treatment-naive with anaplastic lymphoma kinase (ALK)-positive advanced NSCLC.

In Stage 1, erlotinib will be given at a starting dose of 150 milligrams (mg) by mouth (PO) once daily (QD) and the starting dose of alectinib will be 600 mg twice daily (BID), for 28 consecutive days during Cycle 1 and on Days 1 through 21 of each cycle thereafter. The starting dose of atezolizumab will be 1200 mg, administered every 3 weeks (q3W) starting on Day 8 of Cycle 1. If the starting regimen for a combination treatment is not tolerated, alternative doses and/or schedules of erlotinib and atezolizumab or alectinib and atezolizumab may be tested to determine potential recommended Phase 2 dose (RP2D) for that combination treatment. In Stage 2, a potential RP2D and schedule for each combination treatment will be investigated in an expansion cohort.

For both stages, continuation of treatment beyond Cycle 1 will be at the discretion of the treating investigator. Study treatment will be discontinued in participants who experience disease progression or unacceptable toxicity, are not compliant with the study protocol, or, in their opinion or in the opinion of the investigator, are not benefiting from study treatment. However, in the absence of unacceptable toxicity, participants with second-line or greater NSCLC who are still receiving atezolizumab at the time of radiographic disease progression may be permitted to continue study treatment.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Alectinib
    Participants will receive 600 mg PO alectinib BID for 28 consecutive days during Cycle 1 and on Days 1-21 of each cycle thereafter (21-day cycles from Cycle 2 onwards) in Stage 1 and RP2D PO BID in Stage 2.
    Other Name: Alecensa
  • Drug: Atezolizumab
    Participants will receive 1200 mg atezolizumab IV infusion q3w on Day 8 of Cycle 1 and on Day 1 of each cycle thereafter in Stage 1 and in Stage 2.
    Other Names:
    • TECENTRIQ
    • MPDL3280A
  • Drug: Erlotinib
    Participants will receive 150 mg erlotinib PO QD for 28 consecutive days during Cycle 1 and on Days 1-21 of each cycle thereafter in Stage 1 (21-day cycles from Cycle 2 onwards) and RP2D PO QD in Stage 2.
    Other Name: Tarceva
Study Arms  ICMJE
  • Experimental: Stage 1: Alectinib and Atezolizumab
    In Stage 1, starting dose of atezolizumab will be 1200 mg IV q3w administered on Day 8 of Cycle 1 and on Day 1 (21-day cycle) of each cycle thereafter along with alectinib at a starting dose of 600 mg PO BID for 28 consecutive days during Cycle 1 and on Days 1-21 of each cycle thereafter; unless maximum tolerable dose (MTD) is exceeded. The combination will be given to treatment-naive participants with ALK-positive, locally advanced or metastatic NSCLC.
    Interventions:
    • Drug: Alectinib
    • Drug: Atezolizumab
  • Experimental: Stage 1: Erlotinib and Atezolizumab
    In Stage 1, starting dose of atezolizumab will be 1200 mg IV q3w administered on Day 8 of Cycle 1 and on Day 1 (21-day cycles) of each cycle thereafter along with erlotinib at a starting dose of 150 mg PO QD, for 28 consecutive days during Cycle 1 and on Days 1-21 of each cycle thereafter; unless MTD is exceeded. The combination will be given to participants with EGFR TKI treatment-naive, locally advanced or metastatic NSCLC.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Erlotinib
  • Experimental: Stage 2: Alectinib and Atezolizumab
    In Stage 2, participants received the RP2D on the basis of the MTD or maximum allowed dose (MAD) of the combination treatment established in Stage 1. Treatment-naive participants with ALK-positive, locally advanced or metastatic NSCLC will be included.
    Interventions:
    • Drug: Alectinib
    • Drug: Atezolizumab
  • Experimental: Stage 2: Erlotinib and Atezolizumab
    In Stage 2, participants received the RP2D on the basis of the MTD or MAD of the combination treatment established in Stage 1. Previously untreated (or with one prior treatment that was not an EGFR TKI), EGFR mutation positive, locally advanced or metastatic NSCLC participants will be included.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Erlotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 28, 2017)
52
Original Estimated Enrollment  ICMJE
 (submitted: December 16, 2013)
32
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically documented, locally advanced or metastatic NSCLC.
  • Participants in Stage 1 (Safety Evaluation) receiving erlotinib: No limit to the number of prior therapies (except for EGFR TKIs).
  • Participants in Stage 2 (Expansion) receiving erlotinib: i) sensitizing mutation in the EGFR gene and ii) consent to collection of tumor tissue samples before, during, and after treatment for biopsy and PD biomarker analyses.
  • Participants receiving alectinib in either Stage 1 or Stage 2: must be ALK positive as assessed by Food and Drug Administration (FDA) approved test and must not have received prior treatment for their advanced NSCLC.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Measurable disease, as defined by RECIST Version 1.1 (v1.1).
  • Adequate hematologic and end-organ function.
  • Use of highly effective contraception (as defined by protocol) and until 5 months after the last dose of atezolizumab and for 3 months after the last dose of alectinib or for 2 weeks after the last dose of erlotinib, whichever is longer; Males must also refrain from sperm donatation during this same time period. Participants must not be pregnant or breastfeeding.
  • Archival tumor tissue specimen meeting protocol specifications or the participant will be offered the option of a pre-treatment biopsy to obtain adequate tissue sample.

Exclusion Criteria:

  • For participants receiving erlotinib group: prior treatment with any EGFR mutant-targeting TKI
  • Any approved anticancer therapy, including chemotherapy, or hormonal therapy (except hormone-replacement therapy or oral contraceptives) within 3 weeks of first dose.
  • Treatment with any other test drug or participation in another clinical trial within 28 days of enrollment.
  • Known symptomatic central nervous system (CNS) metastases. Participants with a history of treated or untreated asymptomatic CNS metastases may be eligible.
  • Leptomeningeal disease.
  • Uncontrolled tumor-related pain.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage at least once monthly.
  • High levels of calcium requiring bisphosphonate therapy or denosumab.
  • Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in-situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).
  • History of severe allergic, anaphylactic, or other reactions to chimeric or humanized antibodies or fusion proteins.
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
  • History of autoimmune disease.
  • Participants with prior bone marrow or solid organ transplantation.
  • History of lung inflammation or disease.
  • Serum albumin less than (<) 2.5 grams per deciliter (g/dL).
  • Positive for Human Immunodeficiency Virus (HIV).
  • Liver disease.
  • Current or active tuberculosis, hepatitis B, or hepatitis C.
  • Participants with past or resolved hepatitis B virus (HBV) infection are eligible; participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV Riboxy Nucleic Acid (RNA).
  • Signs or symptoms of infection within 2 weeks prior to first dosing.
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to first dosing.
  • Significant cardiovascular disease.
  • Major surgical procedure other than for diagnosis within 28 days prior to first dosing or during the course of the study.
  • Administration of a live, attenuated vaccine within 4 weeks before first dosing or during the study.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may reasonably prevent the participant from participating.
  • Hypersensitivity to erlotinib or alectinib or to any of the excipients.
  • Any significant ophthalmologic abnormality. The use of contact lenses is not recommended during the study.
  • For participants receiving alectinib: baseline Fridericias corrected QT interval (QTcF) greater than (>) 470 milliseconds (ms) or symptomatic bradycardia.
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies.
  • Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dosing.
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to first dosing (inhaled corticosteroids and mineralocorticoids are allowed).
  • Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are elgible for study after discussion and approval by the Medical Monitor.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Hong Kong,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02013219
Other Study ID Numbers  ICMJE WP29158
2013-004382-13 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP