Clinical Trials /

A Study of Daratumumab in Combination With Atezolizumab Compared With Atezolizumab Alone in Participants With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

NCT03023423

Description:

The purpose of the study is to compare the overall response rate (ORR) in non-small cell lung cancer (NSCLC) participants treated with daratumumab in combination with atezolizumab versus atezolizumab alone.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Daratumumab in Combination With Atezolizumab Compared With Atezolizumab Alone in Participants With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer
  • Official Title: A Phase 1b/2, Open-Label, Randomized Study of Daratumumab Administered in Combination With Atezolizumab Compared With Atezolizumab Alone in Subjects With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: CR108256
  • SECONDARY ID: 2016-002579-83
  • SECONDARY ID: 54767414LUC2001
  • NCT ID: NCT03023423

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
AtezolizumabTreatment Arm A: Atezolizumab
DaratumumabJNJ-54767414Treatment Arm B: Atezolizumab and Daratumumab

Purpose

The purpose of the study is to compare the overall response rate (ORR) in non-small cell lung cancer (NSCLC) participants treated with daratumumab in combination with atezolizumab versus atezolizumab alone.

Detailed Description

      This randomized (study medication assigned to participants by chance), multicenter study will
      provide study treatment (atezolizumab alone or atezolizumab+daratumumab) to participants with
      previously treated advanced or metastatic NSCLC to assess the anti-tumor activity and safety.
      Participants who receive atezolizumab treatment with confirmed disease progression based on
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be eligible to crossover to
      treatment (atezolizumab + daratumumab) if they meet crossover eligibility criteria. It is
      expected that the vast majority of approximately 96 participants will enroll in the study,
      including 6 participants in a safety run in phase. Data Monitoring Committee (DMC) will
      review ongoing data, and may formulate recommendations on study conduct, including expansion
      of enrollment of some PD-L1 subgroups, resulting in greater than 96 participants. The
      participants in the safety run in phase will be administered the combination of daratumumab
      and atezolizumab to determine the safety and tolerability that will be evaluated by the
      Safety Evaluation Team (SET) for dose limiting toxicity before the random assignment of
      participants in a 1:1 ratio in 2 treatment arms. The study consists of 3 phases: Screening
      Phase (up to 28 days), Treatment Phase and Post-Treatment Follow-up Phase which will continue
      until death, lost to follow-up, withdrawal of consent, or the End of the Study [the study end
      is approximately 6 to 12 months after that last participant is enrolled]. Participants will
      undergo tumor assessments (RECIST 1.1), immunogenicity, pharmacokinetics, biomarkers and
      safety evaluations (adverse events, laboratory tests, electrocardiogram [ECGs], vital sign
      measurements, physical examinations, Eastern Cooperative Oncology Group [ECOG] performance
      status score) over the time.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment Arm A: AtezolizumabExperimentalParticipants in Treatment Arm A will receive Atezolizumab 1,200 milligram (mg) intravenously (IV) on Day 1 of every 21-day cycle. Participants with confirmed disease progression based on RECIST 1.1 may cross over to Arm B and receive daratumumab and atezolizumab, provided crossover eligibility criteria are met.
  • Atezolizumab
Treatment Arm B: Atezolizumab and DaratumumabExperimentalParticipants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) Intravenously (IV) weekly for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1200 mg IV on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter. Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
  • Atezolizumab
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Have histologically or cytologically confirmed advanced or metastatic non-small cell
             lung cancer (NSCLC) (Stage IIIb or greater)

          -  Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1

          -  Known PD-L1 tumor status as determined by an immunohistochemistry (IHC) assay
             performed by the central laboratory on tissue obtained at Screening

          -  A woman of childbearing potential must have a negative highly sensitive serum
             (beta-human chorionic gonadotropin [beta- hCG]) at Screening within 14 days prior to
             study drug administration

        Inclusion Criteria for Crossover:

          -  Participants must have been randomized to Arm A of the study and had radiographic
             disease progression according to RECIST 1.1

          -  Participants must have a mandatory biopsy at the time of disease progression according
             to RECIST 1.1 prior to crossing over. If not clinically feasible, discussion with
             Sponsor is required

          -  The first dose of atezolizumab in the crossover arm should be within 42 days of last
             dose but no less than 21 days from the last dose prior to crossing over

        Exclusion Criteria:

          -  Received any of the following prescribed medications or therapies in the past:

               1. Anti-cluster of differentiation(CD)38 therapy, including daratumumab

               2. CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4,
                  anti-PD-1, and anti-PD-L1 therapies

          -  Known to be seropositive for human immunodeficiency virus (HIV)

          -  Prior allogeneic bone marrow transplantation or solid organ transplant

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Active hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg]
             or prior history of hepatitis B, defined by presence of antibodies to hepatitis B core
             antigen [anti-HBc], regardless of hepatitis B surface antibody [anti-HBs] status;
             active hepatitis C or prior history of hepatitis C (anti-HCV positive), except in the
             setting of a sustained virologic response (SVR), defined as aviremia 12 weeks after
             completion of antiviral therapy. If hepatitis C virus (HCV) antibodies are detected,
             an HCV RNA test for viral load by polymerase chain reaction (PCR) should be performed
             at least 12 weeks after completion of antiviral therapy to rule out active infection

        Exclusion Criteria for Crossover:

          -  Received any subsequent anti-cancer therapies from the time between the last dose of
             atezolizumab prior to the first administration of study drug after crossing over

          -  Whole brain radiation within 28 days or other radiotherapy within 14 days prior to
             first administration of study drug after crossing over
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Overall Response Rate (ORR)
Time Frame:From randomization to end of study (an expected average of 3 years)
Safety Issue:
Description:ORR is defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to (>=)30 percent (%) decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Measure:Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame:Screening (28 days ) to end of treatment (30 days after the last dose)
Safety Issue:
Description:
Measure:Duration of Response (DoR)
Time Frame:From randomization to the date of first documented evidence of Progressive Disease [PD] (an expected average of 3 years
Safety Issue:
Description:Duration of Response is defined as the duration from the date of the initial documentation of a response to the date of the first objectively documented evidence of progressive disease or death (At least 20% increase in the sum of the longest diameters of index lesions), whichever status is recorded first.
Measure:Percentage of Participants who Achieve Disease Control (CR, PR, or SD with duration of at least 16 weeks) Clinical Benefit Rate (CBR)
Time Frame:From randomization to end of study (an expected average of 3 years)
Safety Issue:
Description:Clinical Benefit Rate is defined as the proportion of participants who achieve disease control (complete response [CR], Disappearance of all lesions; partial response [PR], greater than or equal to (>=) 30% decrease in the sum of the diameters of all index lesions; or stable disease [SD], less than (<) 30% decrease in sum of longest diameters of all index lesions with duration of at least 16 weeks).
Measure:Progression-Free Survival (PFS)
Time Frame:From randomization to the date of first documented evidence of PD (an expected average of 3 years)
Safety Issue:
Description:PFS is defined as the duration from the date of randomization to the date of objectively documented progression or death due to any cause, whichever status is recorded first.
Measure:Overall Survival (OS)
Time Frame:From randomization to the date of first documented evidence of PD (an expected average of 3 years)
Safety Issue:
Description:Overall Survival is defined as the duration from the date of randomization to the date of death due to any cause.
Measure:Maximum Observed Analyte Concentration (Cmax) of Daratumumab
Time Frame:Predose and end of infusion Cycle 1 Day 1(C1D1), Predose-C2D1, C3D1, C3D15, end of infusion-C3D15; predose and end of infusion-C4D1, predose and end of infusion-C8D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose)
Safety Issue:
Description:Maximum observed analyte concentration of daratumumab will be assessed.
Measure:Maximum Observed Analyte Concentration (Cmax) of Atezolizumab
Time Frame:Predose and end of infusion-C1D1, end of infusion - C1D2, predose - C2D1, C3D1 ; pre-dose and end of infusion-C4D1, pre-dose and end of infusion-C8D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose)
Safety Issue:
Description:Maximum observed analyte concentration of atezolizumab will be assessed.
Measure:Minimum Observed Analyte Concentration (Cmin) of Daratumumab
Time Frame:Predose and end of infusion Cycle 1 Day 1(C1D1), Predose-C2D1, C3D1, C3D15, end of infusion-C3D15; predose and end of infusion-C4D1, predose and end of infusion-C8 D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose)
Safety Issue:
Description:Minimum observed analyte concentration of daratumumab will be assessed.
Measure:Minimum Observed Analyte Concentration (Cmin) of Atezolizumab
Time Frame:Predose and end of infusion-C1D1, end of infusion - C1D2, predose - C2D1, C3D1 ; pre-dose and end of infusion-C4D1, pre-dose and end of infusion-C8D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose)
Safety Issue:
Description:Minimum observed analyte concentration of atezolizumab will be assessed.
Measure:Anti-Daratumumab Antibodies Concentration
Time Frame:predose - C1D1, C2D1, C8D1, C12D1, C16D1 up to end of treatment (30 days after the last dose)
Safety Issue:
Description:
Measure:Anti-Atezolizumab Antibodies Concentration
Time Frame:predose - C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1 up to end of treatment (30 days after the last dose)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

March 1, 2018