A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- Atezolizumab
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 578
- Locations
- 183
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a randomized, Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab in combination with cisplatin or carboplatin + pemetrexed compared with treatment with cisplatin or carboplatin + pemetrexed in participants who are chemotherapy-naive and have Stage IV non-squamous NSCLC. Eligible participants will be randomized by a 1:1 ratio into 2 groups: Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) and Arm B (Carboplatin or Cisplatin + Pemetrexed). The study will be conducted in two phases: Induction Phase and Maintenance Phase.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Histologically or cytologically confirmed, Stage IV non-squamous NSCLC. Participants with tumors of mixed non-small cell histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous
- •No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded. Participants with unknown EGFR and ALK status require test results at screening from a local or central laboratory
- •Participants who have received prior neo-adjuvant, radiotherapy, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy
- •Participants should submit a pre-treatment tumor tissue sample if available before or within 4 weeks after enrollment. If tumor tissue is not available, participants are still eligible
- •For participants enrolled in the extended China enrollment phase: current resident of mainland China, Hong Kong, or Taiwan and of Chinese ancestry
- •Measurable disease, as defined by RECIST v1.1
- •Adequate hematologic and end organ function
- •For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of cisplatin
- •For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
Exclusion Criteria
- •Cancer-Specific Exclusions
- •Participants with a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
- •Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- •Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than or equal to (\>= 2) weeks prior to randomization
- •Leptomeningeal disease
- •Uncontrolled tumor-related pain
- •Uncontrolled or symptomatic hypercalcemia (greater than \[\>\] 1.5 millimole/Liter ionized calcium or calcium \>12 milligrams/deciliter or corrected serum calcium \>upper limit of normal)
- •Malignancies other than NSCLC within 5 years prior to randomization
- •Known tumor programmed death-ligand 1 (PD-L1) expression status from other clinical studies (e.g., participants whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD L1 antibodies but were not eligible are excluded)
- •General Medical Exclusions:
Arms & Interventions
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m\^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Atezolizumab
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m\^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Carboplatin
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m\^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Cisplatin
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m\^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Pemetrexed
Arm B (Carboplatin or Cisplatin + Pemetrexed)
Participants received IV infusion of 500 mg/m\^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Carboplatin
Arm B (Carboplatin or Cisplatin + Pemetrexed)
Participants received IV infusion of 500 mg/m\^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Cisplatin
Arm B (Carboplatin or Cisplatin + Pemetrexed)
Participants received IV infusion of 500 mg/m\^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Intervention: Pemetrexed
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Randomization up to approximately 39 months
OS is defined as time from randomization to death from any cause.
Progression Free Survival (PFS) as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame: Randomization up to approximately 39 months
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurred first.
Secondary Outcomes
- Overall Survival Rate at Year 1(Year 1)
- Overall Survival Rate Year 2(Year 2)
- Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1(Randomization up to approximately 25 months)
- Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1(Randomization up to approximately 25 months)
- Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score(Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months))
- Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score(Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months))
- Change From Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score(Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months))
- Minimum Observed Serum Atezolizumab Concentration (Cmin)(Predose (Prd; 0 hour [h]) on D1 of Cy 2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle (up to approximately 25 months))
- Maximum Observed Serum Atezolizumab Concentration (Cmax)(Day 1 of Cycle 1 (Cycle length=21 days))
- Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)(Prd (0 h), 5-10 minutes (mins) before end of carboplatin infusion (infusion duration=1-2 h), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days))
- Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)(Prd (0 h), 5-10 mins before end of cisplatin infusion (infusion duration=30-60 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days))
- Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)(Prd (0 h), 5-10 mins before end of pemetrexed infusion (infusion duration=10 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days))
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab(Prd (0 h) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle, at treatment discontinuation & then every 30 days (up to 120 days) after last dose of atezolizumab (up to app 25 months))