Clinical Trial: NCT02409342 - My Cancer Genome

NCT02409342

Description:

This randomized, open-label study will evaluate the efficacy and safety of atezolizumab compared with chemotherapy consisting of a platinum agent (cisplatin or carboplatin per investigator discretion) combined with either pemetrexed (non-squamous disease) or gemcitabine (squamous disease) in programmed death-ligand 1 (PD-L1)-selected, chemotherapy-naive participants with Stage IV Non-Squamous or Squamous NSCLC.

Related Conditions:

Non-Small Cell Lung Carcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02409342

Trial Eligibility

Document

Title

Brief Title: A Study of Atezolizumab (MPDL3280A) Compared With a Platinum Agent (Cisplatin or Carboplatin) + (Pemetrexed or Gemcitabine) in Participants With Stage IV Non-Squamous or Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower110]
Official Title: A Phase III, Open Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With a Platinum Agent (Cisplatin or Carboplatin) in Combination With Either Pemetrexed or Gemcitabine for PD-L1-Selected, Chemotherapy-Naive Patients With Stage IV Non-Squamous Or Squamous Non-Small Cell Lung Cancer

Clinical Trial IDs

ORG STUDY ID: GO29431
SECONDARY ID: 2014-003083-21
NCT ID: NCT02409342

Conditions

Non-Squamous Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer

Interventions

Drug	Synonyms	Arms
Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody	MPDL3280A, RO5541267	Atezolizumab
Carboplatin		(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Cisplatin		(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Gemcitabine		(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Pemetrexed		(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)

Purpose

Trial Arms

Name	Type	Description	Interventions
(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)	Active Comparator	Participants with non-squamous NSCLC will receive chemotherapy with pemetrexed in combination with either cisplatin or carboplatin (per investigator discretion) on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by maintenance therapy with pemetrexed alone as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months). Participants with squamous NSCLC will receive chemotherapy with gemcitabine on Days 1 and 8 of each 21-day cycle in combination with either cisplatin or carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by best supportive care as per local standard of care until disease progression, unacceptable toxicity, or death (maximum up to approximately 58 months).	Carboplatin Cisplatin Gemcitabine Pemetrexed
Atezolizumab	Experimental	Participants with squamous or non-squamous NSCLC will receive atezolizumab on Day 1 of each 21-day cycle until loss of clinical benefit (as assessed by the investigator), unacceptable toxicity, or death (maximum up to approximately 58 months).	Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed, Stage IV non-squamous or squamous NSCLC

          -  No prior treatment for Stage IV non-squamous or squamous NSCLC. Participant known to
             have a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or an
             anaplastic lymphoma kinase (ALK) fusion oncogene are excluded from the study

          -  Tumor PD-L1 expression as determined by immunohistochemistry (IHC) assay of archival
             tumor tissue or tissue obtained at screening

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST
             v1.1)

          -  Adequate hematologic and end-organ function

        Exclusion Criteria:

          -  Known sensitizing mutation in the EGFR gene or ALK fusion oncogene

          -  Active or untreated central nervous system (CNS) metastases as determined by Computed
             Tomography (CT) or magnetic resonance imaging (MRI) evaluation

          -  Malignancies other than NSCLC within 5 years prior to randomization, with the
             exception of those with a negligible risk of metastasis or death treated with expected
             curative outcome

          -  Pregnant or lactating women

          -  History of autoimmune disease

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is
             permitted

          -  Positive test for Human Immunodeficiency Virus (HIV)

          -  Active hepatitis B or hepatitis C

          -  Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint
             blockade therapies, anti PD1, 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:	Overall Survival (OS) in the TC3 or IC3-WT Populations
Time Frame:	From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	OS is defined as the time from randomization to death from any cause.

Secondary Outcome Measures

Measure:	Progression-free Survival (PFS) in the TC3 or IC3-WT Populations
Time Frame:	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. PFS could not be formally tested.

Measure:	Progression-free Survival (PFS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
Time Frame:	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months)
Safety Issue:
Description:	PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. PFS could not be formally tested.

Measure:	Percentage of Participants With Objective Response (ORR) in the TC3 or IC3-WT Populations
Time Frame:	Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 10 Sep 2018 (up to approximately 38 months)
Safety Issue:
Description:	Objective response (partial response plus complete response) as determined by the investigator according to RECIST v1.1.

Measure:	Percentage of Participants With Objective Response (ORR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
Time Frame:	Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 4 Feb 2020 (up to approximately 54.5 months)
Safety Issue:
Description:	Objective response (partial response plus complete response) as determined by the investigator according to RECIST v1.1.

Measure:	Duration of Response (DOR) in the TC3 or IC3-WT Populations
Time Frame:	From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first.

Measure:	Duration of Response (DOR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
Time Frame:	From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months)
Safety Issue:
Description:	DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first.

Measure:	Percentage of Participants Who Are Alive at 1 Year in the TC3 or IC3-WT Populations
Time Frame:	Baseline to 1 year or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:

Measure:	Percentage of Participants Who Are Alive at 2 Years in the TC3 or IC3-WT Populations
Time Frame:	Baseline to 2 years or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:

Measure:	Percentage of Participants Who Are Alive at 1 Year in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
Time Frame:	Baseline to 1 year or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)
Safety Issue:
Description:

Measure:	Percentage of Participants Who Are Alive at 2 Years in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
Time Frame:	Baseline to 2 years or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)
Safety Issue:
Description:

Measure:	Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Score as Assessed by the Symptoms in Lung Cancer (SILC) Scale Symptom Score in the TC3 or IC3-WT Populations
Time Frame:	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	TTD in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant.

Measure:	Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations
Time Frame:	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	Change from baseline in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant.

Measure:	TTD as Assessed Using EORTC QLQ Supplementary Lung Cancer Module (EORTC QLQ-LC13) in the TC3 or IC3-WT Populations
Time Frame:	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	TTD in patient-reported lung cancer symptoms, defined as time from randomization to deterioration (10-point change) in any of the following symptom subscales (cough, dyspnea [multi-item scale], and chest pain), whichever occurs first, as measured by the EORTC QLQ-LC13. EORTC QLQ-LC13 module incorporates one multi-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.

Measure:	OS in Participants With PD-L1 Expression
Time Frame:	From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	OS according to RECIST v1.1 in the PD-L1 (defined with SP263 IHC assay)

Measure:	Investigator-Assessed PFS in Participants With PD-L1 Expression According to RECIST v1.1
Time Frame:	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	Investigator-assessed PFS according to RECIST v1.1 in the PD-L1 (defined with SP263 IHC assay)

Measure:	OS in Participants With Blood Tumor Mutational Burden (bTMB)
Time Frame:	From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	OS according to RECIST v1.1 in the bTMB subpopulations.

Measure:	Investigator-Assessed PFS in Participants With bTMB According to RECIST v1.1
Time Frame:	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:	PFS according to RECIST v1.1 in the bTMB subpopulations.

Measure:	Minimum Observed Serum Concentration (Cmin) of Atezolizumab
Time Frame:	Prior to infusion (0 hour) on Day 1 of Cycles 2, 3, 4, 8, 16, and every eighth cycle thereafter, and at treatment discontinuation until data cut-off on 10 September 2018 (up to approximately 38 months) (cycle duration = 21 days)
Safety Issue:
Description:

Measure:	Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Time Frame:	0 hour (predose) and 30 minutes after atezolizumab infusion on Day 1 (infusion duration = up to 1 hour)
Safety Issue:
Description:

Measure:	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:	Baseline up to approximately 70 months
Safety Issue:
Description:

Measure:	Percentage of Participants With Anti-therapeutic Antibodies (ATAs)
Time Frame:	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Safety Issue:
Description:

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Hoffmann-La Roche

Last Updated

August 9, 2021

Clinical Trials /

A Study of Atezolizumab (MPDL3280A) Compared With a Platinum Agent (Cisplatin or Carboplatin) + (Pemetrexed or Gemcitabine) in Participants With Stage IV Non-Squamous or Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower110]