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)

• ClinicalTrials.gov Identifier: NCT03456063
• Recruitment Status: Active, not recruiting
• First Posted: March 7, 2018
• Last Update Posted: May 6, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 5, 2018
• First Posted Date: March 7, 2018
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: April 24, 2018
• Estimated Primary Completion Date: January 19, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2021)

Independent Review Facility (IRF)-Assessed Event Free Survival (EFS) [ Time Frame: Up to approximately 96 months ]

IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first.

Original Primary Outcome Measures (submitted: March 5, 2018)

Major pathological response (MPR) [ Time Frame: At time of surgery ]

MPR is defined as ≤ 10% residual viable tumor at the time of surgical resection, as assessed by central pathology laboratory.

Current Secondary Outcome Measures (submitted: March 14, 2022)

• Pathological Complete Response (pCR) [ Time Frame: At time of surgery ]
  pCR is defined as the absence of any viable primary tumor cells at the time of surgical resection in the primary tumor and all sampled lymph nodes as assessed by central and local pathology laboratory.
• Major Pathological Response (MPR) [ Time Frame: At time of surgery ]
  MPR is defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor, as assessed by central and local pathology laboratory.
• Objective Response (OR) [ Time Frame: Prior to surgery, up to approximately 84 days ]
  Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1
• Overall Survival (OS) [ Time Frame: Up to approximately 96 months ]
  OS is defined as the time from randomization to death from any cause during the course of the study.
• Investigator-Assessed EFS [ Time Frame: Up to approximately 96 months ]
  EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, as assessed by the investigator; or death from any cause, whichever occurs first.
• Disease-Free Survival (DFS) [ Time Frame: Up to approximately 96 months ]
  DFS is defined as the time from the first date of no disease to local or distant recurrence (including occurrence of new primary NSCLC) or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up
• 2-Year and 3-Year OS [ Time Frame: Up to approximately 96 months ]
  The 2-year and 3-year OS rate is defined as the probability that a participant will be alive 2 years and 3 years after randomization, respectively.
• 2-Year and 3-Year Independent Review Facility-Assessed EFS [ Time Frame: Up to approximately 96 months ]
  EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Independent Review Facility.
• 2-Year and 3-Year Investigator-Assessed EFS [ Time Frame: Up to approximately 96 months ]
  EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Investigator.
• Change from baseline in HRQoL scores [ Time Frame: Up to approximately 96 months ]
  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
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 96 months ]
• Number and Severity of Surgical Related Adverse Events [ Time Frame: Up to approximately 96 months ]
• Number of Surgical Delays [ Time Frame: Up to approximately 96 months ]
  Number of surgical delays.
• Length of Surgical Delays [ Time Frame: Up to approximately 96 months ]
  Length of surgical delays.
• Number of Operative and Post-Operative Complications [ Time Frame: Up to approximately 96 months ]
  Number of operative and post-operative complications.
• Reasons for Surgical Cancellations [ Time Frame: Up to approximately 96 months ]
  Reasons for surgical cancellations.
• 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 96 months) ]
  Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
• 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 96 months) ]
  Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
• 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 96 months) ]

Original Secondary Outcome Measures (submitted: March 5, 2018)

• Event-Free Survival (EFS) [ Time Frame: Approximately 79 months ]
  EFS is defined as time from randomization to the first documented disease progression or recurrence as determined by the investigator, or death from any cause, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Approximately 79 months ]
  OS is defined as the time from randomization to death from any cause during the course of the study.
• Objective Response (OR) [ Time Frame: From baseline up to approximately 84 days ]
  Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1
• Pathological Complete Response (pCR) [ Time Frame: At time of surgery ]
  pCR is defined as the absence of any viable tumor at the time of surgical resection, as assessed by central and local pathology laboratory.
• MPR [ Time Frame: At time of surgery ]
  MPR at the time of surgical resection as assessed by the investigator site pathology laboratory.
• OS [ Time Frame: From randomization to 2 years ]
  OS is defined as the time from randomization to death from any cause.
• OS [ Time Frame: From randomization to 3 years ]
  OS is defined as the time from randomization to death from any cause.
• EFS [ Time Frame: From randomization to 2 years ]
  EFS is defined as time from randomization to the first documented disease progression or recurrence as determined by the investigator, or death from any cause, whichever occurs first.
• EFS [ Time Frame: From randomization to 3 years ]
  EFS is defined as time from randomization to the first documented disease progression or recurrence as determined by the investigator, or death from any cause, whichever occurs first.
• Disease-Free Survival (DFS) [ Time Frame: Approximately 79 months ]
  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
• Change from baseline in HRQoL scores [ Time Frame: Approximately 79 months ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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 participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Non-Small-Cell Lung

Intervention

• Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

  Atezolizumab will be administered as intravenous (IV) infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle (every 3 weeks) for 4 cycles during the neoadjuvant treatment phase

  Atezolizumab will be administered as IV infusion at a dose of 1200 milligrams (mg) every 3 weeks for 16 cycles during the post-operative adjuvant phase

  Other Name: Tecentriq
• Drug: Placebo Comparator
  Placebo will be administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Drug: Nab-paclitaxel
  Nab-paclitaxel 100 mg/m^2 will be administered intravenously on Days 1, 8, and 15 of each 21 day cycle for 4 cycles during the neoadjuvant treatment phase
  Other Name: Abraxane
• Drug: Pemetrexed
  Pemetrexed 500 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
  Other Name: Alimta
• Drug: Carboplatin
  Carboplatin initial target AUC of 6 mg/mL/min will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Drug: Cisplatin
  Cisplatin 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Drug: Gemcitabine
  Gemcitabine 1250 mg/m^2 will be administered intravenously on Day 1 and 8 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
  Other Name: Gemzar

Study Arms

• Experimental: Arm A: Atezolizumab + platinum-based chemotherapy

  Neoadjuvant 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

  Interventions:

  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  • Drug: Nab-paclitaxel
  • Drug: Pemetrexed
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Gemcitabine
• Placebo Comparator: Arm B: Placebo + platinum-based chemotherapy

  Neoadjuvant 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

  Interventions:

  • Drug: Placebo Comparator
  • Drug: Nab-paclitaxel
  • Drug: Pemetrexed
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Gemcitabine

• Publications *: Romero Roman A, Campo-Canaveral de la Cruz JL, Macia I, Escobar Campuzano I, Figueroa Almanzar S, Delgado Roel M, Galvez Munoz C, Garcia Fontan EM, Muguruza Trueba I, Romero Vielva L, Cano Garcia JR, Martinez Tellez E, Partida Gonzalez C, Jimenez Lopez MF, Jimenez Maestre U, Mongil Poce R, Sanchez Lorente D, Alvarez Kindelan A, Provencio Pulla M. Outcomes of surgical resection after neoadjuvant chemoimmunotherapy in locally advanced stage IIIA non-small-cell lung cancer. Eur J Cardiothorac Surg. 2021 Jul 14;60(1):81-88. doi: 10.1093/ejcts/ezab007.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 16, 2022): 453
• Original Estimated Enrollment (submitted: March 5, 2018): 302
• Estimated Study Completion Date: January 19, 2025
• Estimated Primary Completion Date: January 19, 2025 (Final data collection date for primary outcome measure)

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:

• NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma
• Mixed NSCLC and small cell lung cancer histology
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Brazil, China, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Serbia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Ukraine, United Kingdom, United States
• Removed Location Countries: Turkey

Administrative Information

• NCT Number: NCT03456063
• Other Study ID Numbers: GO40241
• Has Data Monitoring Committee: Yes

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: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023