Study of Atezolizumab Combination Carboplatin + Paclitaxel + Bevacizumab in EGRF Mutation or ALK Translocation NSCLC

NCT03991403 | Unknown Phase 3

• 1 other identifier: 2019-03-027
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, Phase III, multicenter, open-label study designed to evaluate the efficacy of Atezolizumab in combination with carboplatin, paclitaxel, bevacizumab compared with treatment with pemetrexed, cisplatin in approximately 228 TKI(tyrosine kinase inhibitor) pre treated patients with Stage IV non squamous non small cell lung cancer with activating EGFR mutation or ALK translocation.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• progression-free survival, PFS

  To evaluate the efficacy of atezolizumab + carboplatin + paclitaxel + bevacizumab as progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (RECIST v1.1) in the following treatment:Atezolizumab + carboplatin + paclitaxel + bevacizumab versus Pemetrexed + carboplatin or cisplatin

  34month after the first patient is randomized

Secondary Outcomes (3)

• overall survival(OS)

  24month after the last patient is randomized

• objective response rate(ORR)

  24month after the last patient is randomized

• duration of response(DOR)

  24month after the last patient is randomized

Other Outcomes (2)

• The difference in PFS and OS based on the CNS metastasis

  24month after the last patient is randomized

• PFS on CNS(brain, spinal cord, ophthalmic..)

  24month after the last patient is randomized

Study Arms (2)

Atezolizumab group

EXPERIMENTAL

Drug: Atezolizumab(Tecentriq); Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

Control group

ACTIVE COMPARATOR

Drug: Pemetrexed; Drug: Carboplatin or cisplatin

Interventions

Atezolizumab(Tecentriq) DRUG

Atezolizumab(1200 mg IV);Over 60 (± 15) min (for the first infusion); 30 (± 10) min for subsequent infusions if tolerated Frequency: Day 1 of every 21 days Induction: Four or Six Cycles Maintenance : until PD

Atezolizumab group

Pemetrexed DRUG

Induction Period (Four or Six Cycles) (1) Pemetrexed(500 mg/m2 IV); Over approximately10 minutes on Day 1 q3w Maintenance Period (Until PD) Pemetrexed(500 mg/m2 IV); Over approximately10 minutes on Day 1 q3w

Control group

Bevacizumab DRUG

Bevacizumab(15 mg/kg IV);Over 90 (±15) min (for the first infusion); shortening to 60 (± 10) then 30 (± 10) min for subsequent infusions if tolerated

Atezolizumab group

Carboplatin DRUG

Carboplatin(AUC 5 or 5.5 IV a); Over approximately 15-30 min

Atezolizumab group

Paclitaxel DRUG

Paclitaxel(175 mg/m2 IV); Over 3 hours

Atezolizumab group

Carboplatin or cisplatin DRUG

Carboplatin(AUC 5.5 IV);Over approximately 30-60 minutes on Day 1 q3W or Cisplatin(75 mg/m²) ; Over 1-2 hours on Day 1 q3w

Control group

Eligibility Criteria

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

You may qualify if:

• Male or female, 18 years of age or older
• Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1
• Histologically or cytologically confirmed, Stage IV non-squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition).
• Patients with tumors of mixed histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous.
• As the stage IV non-squamous NSCLC treatment, no prior cytotoxic treatment is allowed and the patients treated with below tyrosine kinase inhibitor prior to the enrollment
• Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs, such as erlotinib, gefitinib, osimertinib or another EGFR tyrosine kinase inhibitor (TKI) appropriate for the treatment of EGFR mutant NSCLC.
• If the patients have identified T790M mutation after 1st or 2nd generation EGFR TKI failure, the patient must be treated with the second line 3rd generation EGFR TKI treatment, such as osimertinib, before the study participation.
• Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene.
• Patients with unknown EGFR and/or ALK status require test results at screening. ALK and/or EGFR may be assessed locally or at a main investigator laboratory.
• Inoperable stage III non-squamous NSCLC treatment, no prior cytotoxic treatment is allowed and the patients treated with below tyrosine kinase inhibitor prior to the enrollment
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, 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 chemotherapy, radiotherapy, or chemoradiotherapy.
• Patients with a history of treated asymptomatic Central Nervous System(CNS) metastases are eligible, provided they meet all of the following criteria:
• No ongoing requirement for corticosteroids as therapy for Central Nervous System(CNS) disease No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization No evidence of interim progression between the completion of Central Nervous System(CNS)-directed therapy and the screening radiographic study
• Patients with new asymptomatic Central Nervous System(CNS) metastases detected at the screening scan may be eligible without the need for an additional radiation therapy and/or surgery for Central Nervous System(CNS) metastases by investigator's decision.
• Patients who are available to provide tissue from previously obtained archival tumor tissue or tissue obtained from a biopsy at screening for the PD-L1 test.

You may not qualify if:

• Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX®) are allowed. Uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL) Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5 year OS \> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, Gangnamgu, 06351, South Korea

Location

Related Publications (2)

• Bang YH, Park GH, Oh JW, Hwang S, Jeong JG, Lee B, Joe CY, Kim H, Kim J, Park S, Jung HA, Sun JM, Ahn JS, Ahn MJ, Choi YL, Ahn CH, Ali SM, Ock CY, Lee SH. Artificial intelligence-powered spatial analysis of tumor microenvironment in patients with non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitor. J Immunother Cancer. 2025 Oct 31;13(10):e012374. doi: 10.1136/jitc-2025-012374.

  PMID: 41173494 DERIVED

• Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. doi: 10.1200/JCO.23.01891. Epub 2023 Oct 20.

  PMID: 37861993 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Pemetrexed; Bevacizumab; Carboplatin; Paclitaxel; Cisplatin

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)

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

Study Officials

• Myung-Ju Ahn, MD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. Professor Division of Hematology-Oncology Department of Medicine

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 19, 2019
• Study Start: August 27, 2019
• Primary Completion: March 11, 2023
• Study Completion: March 11, 2024
• Last Updated: April 3, 2023

Record last verified: 2023-03

Locations

KR (1)