A Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment with Atezolizumab or Placebo in Combination with Platinum-Based Chemotherapy in Patients with Resectable Stage II, IIIA, or Select IIIB Non-small cell lung cancer

• Register: EUCTR
• Last refreshed on: 28 March 2022
• Main ID: EUCTR2017-002857-12-HU
• Date of registration: 17/04/2018
• Prospective Registration: No
• Primary sponsor: F. Hoffman-La Roche Ltd.
• Public title: A Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment with Atezolizumab or Placebo in Combination with Platinum-Based Chemotherapy in Patients with Resectable Stage II, IIIA, or Select IIIB Non-small cell lung cancer
• Scientific title: A PHASE III, DOUBLE-BLINDED, MULTICENTER, RANDOMIZED STUDY EVALUATING THE EFFICACY AND SAFETY OF NEOADJUVANT TREATMENT WITH ATEZOLIZUMAB OR PLACEBO IN COMBINATION WITH PLATINUM-BASED CHEMOTHERAPY IN PATIENTS WITH RESECTABLE STAGE II, IIIA, OR SELECT IIIB NON-SMALL CELL LUNG CANCER
• Date of first enrolment: 16/04/2018
• Target sample size: 374
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002857-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Placebo + platinum-based chemotherapy; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Brazil, China, Costa Rica, France, Germany, Guatemala, Hungary, Israel, Italy, Korea, Republic of, Mexico, Panama, Peru, Poland, Slovenia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
• Age >= 18 years
• Ability to comply with the study protocol, in the investigator’s judgment
• Pathologically documented Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology
Staging should be based on the 8th edition of the American Joint Committee on Cancer / Union Internationale Contre le Cancer NSCLC staging system
- T4 primary NSCLC will be allowed only on the basis of size (tumors > 7 cm). Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted
- Patients with mixed NSCLC histology or NSCLC not otherwise specified are eligible
- Patients may be screened based on clinical stage, but mandatory pre-operative documentation of N2 nodal involvement by invasive mediastinal staging is required for N2 PET positive nodes. Pre-operative staging of levels 5/6 nodes is optional.
• Solid or subsolid appearance of NSCLC on CT scan with no appearance of purely ground-glass opacity (GGO)
For subsolid lesions, the tumor size should be measured based on solid component only, exclusive of the GGO component.
• Evaluation by the operating attending surgeon and involved medical oncologist prior to study enrollment to verify study eligibility for R0 resection with curative intent
• Pulmonary function tests (PFTs) within 6 months of planned resection and repeated at screening, if clinically indicated, including lung volumes, spirometry, and a diffusion capacity
If PFTs were performed before 6 months of planned resection or have never been performed, they must be performed during the screening period.
• Adequate cardiac function to be eligible for surgical resection with curative intent
If clinically indicated, patients with underlying ischemic, valvular, or other significant heart diseases should be evaluated preoperatively by a cardiologist
• Measurable disease as assessed by the investigator per RECIST v1.1
• Eligibility to receive a platinum-based chemotherapy regimen
• Availability of a representative tumor specimen suitable for determination of PD-L1 status via central testing (results of PD-L1 testing are not required for patient to be randomized into the study)
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
- Absolute neutrophil count >= 1.5 × 109/L (1500/µL) without granulocyte colony-stimulating factor support
- Lymphocyte count >= 0.5 × 109/L (500/µL)
- Platelet count >= 100 × 109/L (100,000/µL) without transfusion
- Hemoglobin >= 90 g/L (9.0 g/dL)
Patients may be transfused to meet this criterion.
- Aspartate transaminase Test, Alanine aminotransferase Test, and Alkaline phosphatase level <= 2.5 × upper limit of normal (ULN)
- Serum bilirubin <= 1.5 × ULN with the following exception:
Patients with known Gilbert disease: serum bilirubin level <= 3 × ULN
- Creatinine clearance >= 45 mL/min
- For patients intended to receive cisplatin: creatinine clearance >= 60 mL/min
- Serum albumin >= 25 g/L (2.5 g/dL)
- For patients not receiving therapeutic anticoagulation: INR or aPTT <=1.5 × ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative tota
Exclusion criteria:
• Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures
• Any prior therapy for lung cancer, including chemotherapy, or radiotherapy
• Major surgical procedure, other than for diagnosis, within 28 days prior to initiation of study treatment, or anticipation of need for non-protocol-mandated major surgical procedure during the study
• Non-squamous NSCLC histology with an activating mutation in the epidermal growth factor receptor or with an anaplastic lymphoma kinase (ALK) fusion oncogene
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
• History of idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
• Active tuberculosis
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• 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 such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, 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 last dose of atezolizumab
• Current treatment with anti-viral therapy for HBV
• Treatment with investigational therapy within 42 days prior to initiation 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
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to initiation of study treatment
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the chemotherapy regimen the patient will be assigned to
• For patients intended to receive cisplatin, any hearing impairment
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after last dose of atezolizumab, 30 days after the last dose of nab-paclitaxel, or 6 months after last dose of p

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Early Stage Resectable Non-small cell lung cancer (NSCLC)
MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Atezolizumab
Product Code: RO5541267/F03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A, Tecentriq
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Abraxane
Product Name: nab-paclitaxel
Product Code: Ro 024-7506
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: nab-paclitaxel
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 0.3-1.2

Trade Name: Tecentriq
Product Name: Atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A, Tecentriq
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Secondary Objective: To evaluate:
• The efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy based on, overall survival (OS), independent review facility -assessed(IRF) EFS, objective response rate, centrally-assessed pathological complete response (pCR), investigator-assessed MPR and pCR, 2 and 3-year OS and investigator-assessed EFS, disease-free survival (DFS)
• Patient reported outcome of GHS/HRQoL associated with atezolizumab in combination with platinum-based chemotherapy
• The safety of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy based on severity of determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
• The safety of adjuvant treatment with atezolizumab
• The immune response to atezolizumab
• The pharmacokinetic profile of atezolizumab when given in combination with platinum-based chemotherapy

Timepoint(s) of evaluation of this end point: 1. Up to 26 months
2. Up to 79 months

Main Objective: • To evaluate the efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy based on central pathology-assessed major pathological response (MPR) and investigator-assessed event-free survival (EFS)

Primary end point(s): 1. MPR, as assessed by central pathology laboratory
2. EFS, as assessed by the investigator

Secondary Outcome(s)

Secondary end point(s): 1. OS
2. IRF-assessed EFS
3. Objective response by the investigator according to RECIST v1.1
4. pCR, as assessed by central pathology laboratory
5. MPR and pCR, as assessed by the investigator site pathology laboratory
6. 2-year and 3-year OS and investigator-assessed EFS
7. DFS as determined by the investigator
8. Change from baseline in health-related quality of life (HRQoL) scores as assessed through use of the two-item global health status (GHS)/HRQoL subscale (Questions 29 and 30) of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 at each assessment timepoint during the study through the completion of adjuvant treatment and observation follow up assessments
9. Occurrence and severity of adverse events, including serious adverse events and immune-related adverse events, with severity determined according to NCI CTCAE v5.0
10. Pharmacokinetics and pharmacodynamics of atezolizmab
11. Incidence of anti-drug antibodies (ADAs) against atezolizumab during the study

Timepoint(s) of evaluation of this end point: 1-2. Up to 79 months
3. Up to 4 months
4-5. Up to 26 months
6. At 2 and 3 year
7-9. Up to 79 months
10-11. Day 1 of Cycles 1 and 3; Day 1 of Cycles5, 7, 11, and 19; at disease progression/recurrence or treatment/observation follow-up discontinuation visit (<=30 days after last dose)

Secondary ID(s)

GO40241

2017-002857-12-DE

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.

Ethics review

Status: Approved
Approval date: 03/04/2018
Contact: