A Study of Bevacizumab, Carboplatin, and Paclitaxel or Pemetrexed With or Without Atezolizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer (IMpower151)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04194203

Collaborator

(none)

304

Enrollment

Locations

Arms

44.6

Anticipated Duration (Months)

13.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of atezolizumab when given in combination with bevacizumab, investigator's choice of either paclitaxel or pemetrexed, and carboplatin compared with placebo given in combination with bevacizumab, paclitaxel or pemetrexed, and carboplatin in patients with chemotherapy-naive, Stage IV non-squamous Non-Small Cell Lung Cancer (NSCLC). The study will be conducted in two phases: Induction Phase and Maintenance Phase.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Atezolizumab Drug: Placebo Drug: Bevacizumab Drug: Paclitaxel Drug: Pemetrexed Drug: Carboplatin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

304 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-Blind Study of Bevacizumab, Carboplatin, and Paclitaxel or Pemetrexed With or Without Atezolizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer (IMpower151)

Actual Study Start Date :

Apr 9, 2020

Anticipated Primary Completion Date :

Feb 15, 2023

Anticipated Study Completion Date :

Dec 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A Participants will receive atezolizumab, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with atezolizumab, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab Atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit. Other Names: Tecentriq Drug: Bevacizumab Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. Other Names: Avastin Drug: Paclitaxel Paclitaxel will be administered by IV infusion at a dose of 175 mg/m2. Drug: Pemetrexed Pemetrexed will be administered by IV infusion at a dose of 500 mg/m2. Drug: Carboplatin Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min.
Placebo Comparator: Treatment B Participants will receive placebo, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with placebo, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit.	Drug: Placebo Placebo matching to atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit. Drug: Bevacizumab Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. Other Names: Avastin Drug: Paclitaxel Paclitaxel will be administered by IV infusion at a dose of 175 mg/m2. Drug: Pemetrexed Pemetrexed will be administered by IV infusion at a dose of 500 mg/m2. Drug: Carboplatin Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min.

Arm

Intervention/Treatment

Experimental: Treatment A

Participants will receive atezolizumab, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with atezolizumab, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit.

Drug: Atezolizumab

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.

Other Names:

Tecentriq

Drug: Bevacizumab

Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.

Other Names:

Avastin

Drug: Paclitaxel

Paclitaxel will be administered by IV infusion at a dose of 175 mg/m2.

Drug: Pemetrexed

Pemetrexed will be administered by IV infusion at a dose of 500 mg/m2.

Drug: Carboplatin

Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min.

Placebo Comparator: Treatment B

Participants will receive placebo, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with placebo, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit.

Drug: Placebo

Placebo matching to atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.

Drug: Bevacizumab

Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.

Other Names:

Avastin

Drug: Paclitaxel

Paclitaxel will be administered by IV infusion at a dose of 175 mg/m2.

Drug: Pemetrexed

Pemetrexed will be administered by IV infusion at a dose of 500 mg/m2.

Drug: Carboplatin

Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min.

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) in the intent to treat (ITT) population, as determined by the investigator [Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)]
PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1

Secondary Outcome Measures

Overall Survival (OS) in the ITT population [Randomization to death from any cause (up to approximately 33 months)]
OS after randomization, defined as the time from randomization to death from any cause.
PFS in the ITT population, as determined by IRF [Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)]
PFS after randomizationdefined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the an Independent Review Facility (IRF) according to RECIST v1.1
PFS in subgroup of participants with PD-L1 Expression, as determined by the investigator [Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)]
PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with PD-L1 expression defined by the SP263 immunohistochemistry (IHC) assay.
PFS in the subgroup of participants with genomic alterations in EGFR or ALK gene, as determined by the investigator [Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)]
PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with genomic alterations in EGFR (i.e., sensitizing EGFR mutations) or ALK gene.
Objective Response Rate (ORR) in the ITT population [Randomization until disease progression or death, which ever occurs first (up to approximately 33 months)]
ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.
Duration of response (DOR) in the ITT population [Randomization until the first occurence of a documented objective response to disease progression or death from any cause, whichever occures first (up to approximately 33 months)]
DOR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Time to Confirmed Deterioration (TTCD) in physical functioning in the ITT population [Randomization up until approximately 33 months]
(TTCD) in physical functioning, defined as the time from randomization to the first observed >=10-point decrease in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) for cancer linearly transformed physical functioning scale score that is sustained for two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death within three weeks.
Percentage of Participants With Adverse Events [Randomization up to approximately 33 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed Stage IV non-squamous NSCLC
No prior treatment for Stage IV non-squamous NSCLC, with the following exceptions: (1) Patients with a sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or were intolerant to treatment with one or more EGFR TKIs, such as erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib, or another EGFR TKI appropriate for the treatment of EGFR-mutant NSCLC. Patients who have progressed on or were intolerant to first-line osimertinib or other third-generation EGFR TKIs are eligible. Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs, such as erlotinib, gefitinib, afatinib, dacomitinib, and who have no evidence of the EGFR T790M mutation in the tumor tissue after TKI therapy are eligible. Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs and who have evidence of the T790M mutation in their tumor tissue must have also progressed on or were intolerant to osimertinib to be eligible. (2) Patients with an ALK gene rearrangement must have experienced disease progression or were intolerant to treatment with one or more ALK inhibitors, such as crizotinib, alectinib, ceritinib, brigatinib, ensartinib and lorlatinib that are appropriate for the treatment of NSCLC that has an ALK gene rearrangement.
Availability of a representative tumor specimen that is suitable for the determination of PD-L1 status, as well as the presence of EGFR mutations and ALK gene rearrangements, via central testing.
Treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy treatment for patients who have received prior neoadjuvant and/or adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease
Measurable disease, as defined by RECIST v1.1
Eastern Cooperative Oncology Group Performance Status of 0 or 1
Life expectancy >=3 months
Adequate hematologic and end-organ function
Negative HIV test at screening
Negative hepatitis B surface antigen (HBsAg) test at screening
Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

Symptomatic, untreated, or actively progressing CNS metastases
History of leptomeningeal disease
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled or symptomatic hypercalcemia
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Active tuberculosis
Significant cardiovascular disease
Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
Prior allogeneic stem cell or solid organ transplantation
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
Current treatment with anti-viral therapy for HBV
Treatment with any approved anti-cancer therapy or investigational therapy within 28 days prior to initiation of study treatment, except for treatment with TKI that should be discontinued for at least 8 days or for approximately 5 x half-life, whichever is the longer, before the first dose of study treatment
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or 6 months after the final dose of bevacizumab, carboplatin, pemetrexed, and paclitaxel

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Peking Union Medical College Hospital	Beijing City	China	100032
2	Beijing Cancer Hospital	Beijing	China	100142
3	Beijing Chest Hospital; Oncology Department	Beijing	China	101149
4	the First Hospital of Jilin University	Changchun	China	130021
5	Jilin Cancer Hospital	Changchun	China	132013
6	West China Hospital, Sichuan University	Chengdu	China	610041
7	The 900th Hospital of PLA joint service support force	Fuzhou	China	110016
8	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	China	510120
9	Sir Run Run Shaw Hospital	Hangzhou	China	310016
10	Harbin Medical University Cancer Hospital	Harbin	China	150081
11	Shandong Cancer Hospital	Jinan	China	250117
12	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City	China	210008
13	Guangxi Cancer Hospital of Guangxi Medical University	Nanning	China	530021
14	Nan Tong Tumor Hospital	Nantong City	China	226361
15	Fudan University Shanghai Cancer Center	Shanghai City	China	200120
16	Shanghai Pulmonary Hospital	Shanghai	China	200433
17	Liaoning cancer Hospital & Institute	Shenyang	China	110042
18	Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center	Wuhan	China	430023
19	Hubei Cancer Hospital	Wuhan	China	430079
20	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an	China	710061
21	The First Affiliated Hospital of Xiamen University	Xiamen	China	361003
22	Zhejiang Cancer Hospital	Zhejiang	China	310022
23	Henan Cancer Hospital	Zhengzhou	China	450008