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)

NCT04194203 | Completed Phase 3 DMC

• 1 other identifier: YO30157
• Study Type: interventional
• Target: 305
• Locations: 1 country
• Sites: 23

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) in the intent to treat (ITT) population, as determined by the investigator

  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

  Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)

Secondary Outcomes (8)

• Overall Survival (OS) in the ITT population

  Randomization to death from any cause (up to approximately 33 months)

• 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 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 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)

• Objective Response Rate (ORR) in the ITT population

  Randomization until disease progression or death, which ever occurs first (up to approximately 33 months)

Study Arms (2)

Treatment A

EXPERIMENTAL

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; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Carboplatin

Treatment B

PLACEBO COMPARATOR

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; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Carboplatin

Interventions

Atezolizumab DRUG

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.

Also known as: Tecentriq

Treatment A

Placebo DRUG

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.

Treatment B

Bevacizumab DRUG

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

Also known as: Avastin

Treatment A; Treatment B

Paclitaxel DRUG

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

Treatment A; Treatment B

Pemetrexed DRUG

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

Treatment A; Treatment B

Carboplatin DRUG

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

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (23)

Peking Union Medical College Hospital

Beijing, 100032, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Beijing Chest Hospital; Oncology Department

Beijing, 101149, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

The 900th Hospital of PLA joint service support force

Fuzhou, 110016, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120, China

Location

Sir Run Run Shaw Hospital

Hangzhou, 310018, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Shandong Cancer Hospital

Jinan, 250117, China

Location

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing, 210008, China

Location

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, 530021, China

Location

Nan Tong Tumor Hospital

Nantong, 226361, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Liaoning cancer Hospital & Institute

Shenyang, 110042, China

Location

Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center

Wuhan, 430023, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, 361003, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Bevacizumab; Paclitaxel; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Coordination Complexes

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: December 11, 2019
• Study Start: April 9, 2020
• Primary Completion: February 2, 2023
• Study Completion: June 27, 2024
• Last Updated: July 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (23)