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A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)

NCT03456063

Description:

This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in patients with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant atezolizumab or best supportive care and monitoring.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)
  • Official Title: A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non−Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO40241
  • NCT ID: NCT03456063

Conditions

  • Non-Small-Cell Lung

Interventions

DrugSynonymsArms
Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyTecentriqArm A: Atezolizumab + platinum-based chemotherapy
Placebo ComparatorArm B: Placebo + platinum-based chemotherapy
Nab-paclitaxelAbraxaneArm A: Atezolizumab + platinum-based chemotherapy
PemetrexedAlimtaArm A: Atezolizumab + platinum-based chemotherapy
CarboplatinArm A: Atezolizumab + platinum-based chemotherapy
CisplatinArm A: Atezolizumab + platinum-based chemotherapy
GemcitabineGemzarArm A: Atezolizumab + platinum-based chemotherapy

Purpose

This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in patients with resectable Stage II, IIIA, or select IIIB non−small cell lung cancer (NSCLC) followed by open-label adjuvant atezolizumab or best supportive care and monitoring.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Atezolizumab + platinum-based chemotherapyExperimentalNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: carboplatin + pemetrexed carboplatin + nab-paclitaxel cisplatin + pemetrexed cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
  • Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  • Nab-paclitaxel
  • Pemetrexed
  • Carboplatin
  • Cisplatin
  • Gemcitabine
Arm B: Placebo + platinum-based chemotherapyPlacebo ComparatorNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: carboplatin + pemetrexed carboplatin + nab-paclitaxel cisplatin + pemetrexed cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
  • Placebo Comparator
  • Nab-paclitaxel
  • Pemetrexed
  • Carboplatin
  • Cisplatin
  • Gemcitabine

Eligibility Criteria

        Inclusion criteria:

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

          -  Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB
             (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on
             the 8th edition of the AJCC/UICC staging system

          -  Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection
             with curative intent

          -  Adequate pulmonary and cardiac function to undergo surgical resection

          -  Measurable disease as defined by RECIST v1.1

          -  Adequate hematologic and end organ function

          -  Negative HIV test at screening

          -  Negative for active HBV and HCV at screening

          -  Adequate tissue for PD-L1 IHC assessment

        Exclusion criteria:

          -  Any prior therapy for lung cancer

          -  Malignancies other than NSCLC within 5 years prior to randomization, with the
             exception of those with a negligible risk of metastasis or death treated expected
             curative outcome

          -  Non-squamous NSCLC histology with activating ALK and EGFR mutation

          -  Pregnant or lactating women

          -  History of autoimmune disease

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or evidence of active of active pneumonitis on screening chest Computed
             Tomography (CT) scan

          -  Prior treatment with cluster of differentiation 137 (CD137) agonist or immune
             checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1
             therapeutic antibody

          -  Severe infection within 4 weeks prior to randomization

          -  Significant history of cardiovascular disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathological response (MPR)
Time Frame:At time of surgery
Safety Issue:
Description:MPR is defined as ≤ 10% residual viable tumor at the time of surgical resection, as assessed by central pathology laboratory.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Approximately 84 months
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause during the course of the study.
Measure:Independent Review Facility (IRF)-Assessed EFS
Time Frame:Approximately 84 months
Safety Issue:
Description:IRF-assessed EFS is defined as the time from the date of randomization to any of the following events, whichever occurs first: progression of disease that precludes surgery per RECIST v1.1, as assessed by the IRF; local or distant disease recurrence, as assessed by the IRF; or death due to any cause.
Measure:Objective Response (OR)
Time Frame:Prior to surgery, up to approximately 84 days
Safety Issue:
Description:Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1
Measure:Pathological Complete Response (pCR)
Time Frame:At time of surgery
Safety Issue:
Description:pCR is defined as the absence of any viable tumor at the time of surgical resection, as assessed by central and local pathology laboratory.
Measure:MPR
Time Frame:At time of surgery
Safety Issue:
Description:MPR at the time of surgical resection as assessed by the investigator site pathology laboratory.
Measure:2-Year OS
Time Frame:Approximately 84 months
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause. 2-Year OS will be analyzed together with OS.
Measure:3-Year OS
Time Frame:Approximately 84 months
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause. 3-Year OS will be analyzed together with OS.
Measure:2-Year Investigator-Assessed EFS
Time Frame:Approximately 84 months
Safety Issue:
Description:EFS is defined as the time from the date of randomization to any of the following events, whichever occurs first: progression of disease that precludes surgery per RECIST v1.1, as assessed by the investigator; local or distant disease recurrence, as assessed by the investigator; or death due to any cause. 2-Year Investigator-Assessed EFS will be analyzed together with EFS.
Measure:3-Year Investigator-Assessed EFS
Time Frame:Approximately 84 months
Safety Issue:
Description:EFS is defined as the time from the date of randomization to any of the following events, whichever occurs first: progression of disease that precludes surgery per RECIST v1.1, as assessed by the investigator; local or distant disease recurrence, as assessed by the investigator; or death due to any cause. 3-Year Investigator-Assessed EFS will be analyzed together with EFS.
Measure:Disease-Free Survival (DFS)
Time Frame:Approximately 84 months
Safety Issue:
Description:DFS is defined as the time from the first date of no disease to local or distant recurrence or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up
Measure:Change from baseline in HRQoL scores
Time Frame:Approximately 84 months
Safety Issue:
Description:Change from baseline in HRQoL scores as assessed through use of the two-item GHS/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow-up assessments
Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:Up to approximately 84 months
Safety Issue:
Description:
Measure:Minimum Observed Serum Atezolizumab Concentration (Cmin)
Time Frame:Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 84 months)
Safety Issue:
Description:Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
Measure:Maximum Observed Serum Atezolizumab Concentration (Cmax)
Time Frame:Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 84 months)
Safety Issue:
Description:Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
Measure:Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
Time Frame:Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 84 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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