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.
Recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Atezolizumab | Tecentriq | Treatment A |
| Placebo | Treatment B | |
| Bevacizumab | Avastin | Treatment A |
| Paclitaxel | Treatment A | |
| Pemetrexed | Treatment A | |
| Carboplatin | Treatment A |
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
|
| 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. |
|
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, 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Progression Free Survival (PFS) in the intent to treat (ITT) population, as determined by the investigator |
| Time Frame: | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Overall Survival (OS) in the ITT population |
| Time Frame: | Randomization to death from any cause (up to approximately 33 months) |
| Safety Issue: | |
| Description: | OS after randomization, defined as the time from randomization to death from any cause. |
| Measure: | PFS in the ITT population, as determined by IRF |
| Time Frame: | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | PFS in subgroup of participants with PD-L1 Expression, as determined by the investigator |
| Time Frame: | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | PFS in the subgroup of participants with genomic alterations in EGFR or ALK gene, as determined by the investigator |
| Time Frame: | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Objective Response Rate (ORR) in the ITT population |
| Time Frame: | Randomization until disease progression or death, which ever occurs first (up to approximately 33 months) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of response (DOR) in the ITT population |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Time to Deterioration (TTD) in physical functioning in the ITT population |
| Time Frame: | Randomization up until approximately 33 months |
| Safety Issue: | |
| Description: | (TTD) 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 followed by death while the patient is on study treatment. |
| Measure: | Percentage of Participants With Adverse Events |
| Time Frame: | Randomization up to approximately 33 months |
| Safety Issue: | |
| Description: |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
August 6, 2021
