| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Malignant neoplasm of bronchus and lung (nsc) adv. |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| -To evaluate the long-term safety of atezolizumab in previously treated patients with advanced NSCLC |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of atezolizumab in previously treated patients with advanced NSCLC
- To further evaluate the efficacy of atezolizumab in previously treated patients with advanced NSCLC
- To further evaluate the long-term safety and efficacy of atezolizumab in previously treated patients with advanced NSCLC |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
STOOL SAMPLE COLLECTION FOR THE ROCHE RESEARCH BIOSAMPLE REPOSITORY IN ASSOCIATION WITH PROTOCOL MO39171
Version 2 dated 14. Jan 2019
The objective of this study is to obtain stool samples from patients who participate in Study MO39171 for the Roche RBR in order to assess the
micobiome, metabolites and other biomarkers in the stool of patients. |
|
| E.3 | Principal inclusion criteria |
-Signed Informed Consent Form
- Age ≥ 18 years
- Able to comply with the study protocol, in the investigator's judgment
- Histologically or cytologically documented Stage IIIb or Stage IV
NSCLC that has progressed following standard systemic chemotherapy
(including if given in combination with anti-PD-1 therapy after anti-PD-1
as monotherapy, or after TKI therapy). Patients with a previously
detected sensitizing EGFR mutation or ALK fusion oncogene must have
received targeted therapy(TKI), followed by at least one line of standard systemic chemotherapy, prior to receiving atezolizumab. Overall,
patients should not have received more than two lines of standard
systemic chemotherapy. Patients who have discontinued first-line or
second-line therapy due to intolerance are also eligible.
–Staging must be according to the UICC/AJCC system, 7th edition
(Detterbeck et al. 2009) (see Appendix 8)
–Pathological characterization may be conducted on tumor specimens
from earlier stage disease, but the tumor samples must be sufficient to
distinguish squamous or non-squamous histology
–Chemotherapy regimens will be counted based on interval disease
progression, and not on the number of agents or the number of switches
in agents (e.g., a first-line or second-line therapy that consists of several
cycles of a platinum doublet and subsequent maintenance therapy that
introduces or switches to a new chemotherapy agent without interval
disease progression will all be considered one chemotherapy regimen)
–Patients with a previously-detected sensitizing EGFR mutation must
have experienced disease progression (during or after treatment) on an
EGFR TKI (erlotinib, gefitinib, osimertinib, etc.)
–Patients with a previously detected ALK fusion oncogene must have
experienced disease progression (during or after treatment) with
crizotinib, alectinib, or another ALK inhibitor
–Prior radiation therapy is allowed, provided that the patient has
recovered from any toxic effects thereof. Combined
radiation/chemotherapy treatment constitutes a single regimen
–Combined radiation/chemotherapy treatment (chemoradiation) counts
as one prior chemotherapy regimen if < 6 months have elapsed between
the last dose and the date of recurrence
–Adjuvant/neoadjuvant chemotherapy is not counted as a line of
treatment
–Debulking surgery and anticancer agents used for pleurodesis are not
counted as lines of therapy
- The last dose of prior systemic anticancer therapy or targeted therapy
must have been administered ≥ 21 days prior to randomization.
- Measurable disease, as defined by Response Evaluation Criteria for
Solid Tumors, Version 1.1 (RECIST v1.1)
- Patients with asymptomatic CNS metastases (treated or untreated), as
determined by CT or MRI evaluation during screening and prior
radiographic evaluation, are eligible
- ECOG performance status 0, 1, or 2 [Appendix 7]
- For women of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive methods
that result in a failure rate of < 1% per year during the treatment period
and for at least 5 months after the last dose of atezolizumab
–A woman is considered to be of childbearing potential if she is
postmenarchal, has not reached a postmenopausal state (≥ 12
continuous months of amenorrhea with no identified cause other than
menopause), and has not undergone surgical sterilization (removal of
ovaries and/or uterus)
–Examples of contraceptive methods with a failure rate of 1% per
year include bilateral tubal ligation, male sterilization, established,
proper use of hormonal contraceptives that inhibit ovulation, hormonereleasing
intrauterine devices, and copper intrauterine devices
–The reliability of sexual abstinence should be evaluated in relation to
the duration of the clinical trial and the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not
acceptable methods of contraception
- HIV-positive patients are allowed, so long as they are stable on antiretroviral
therapy, have a CD4 count ≥ 200 cells/μL, and have an
undetectable viral load at the time of screening |
|
| E.4 | Principal exclusion criteria |
- Symptomatic CNS metastases
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 2 weeks prior to randomization
- Leptomeningeal disease
- Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures
- Pregnant or lactating, or intending to become pregnant during the study
–Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study drug
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
- Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
–Patients with known coronary artery disease or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
- Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- History of autoimmune disease (Appendix 5) are allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks, with the exception of:
- Patients taking concurrent abatacept or belatacept treatment, unless therapy has been withdrawn for > 8 weeks
–Patients with a history of serious or life threatening immune-related events
–No more than 1 concomitant autoimmune disease at the time of study entry is allowed unless one of them is:
Autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone
Controlled Type I diabetes mellitus on a stable dose of insulin regimen
A medical history of such entities as atopic disease or childhood arthralgias, where the clinical suspicion of autoimmune disease is low. In addition, transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent are not excluded (e.g., acute Lyme arthritis)
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to initiation of study treatment
–Prior cancer vaccines and cellular immunotherapy are permitted
- Specifically for patients without autoimmune disease: treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [TNF] agents) within 2 weeks prior to study treatment initiation, or anticipated requirement for systemic immunosuppressive medications during the trial
–For patients with CNS metastases, use of prednisone at a stable dose
(or dose equivalent) of ≤ 20 mg/day is acceptable
–The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency and topical steroids for cutaneous diseases are allowed
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Incidence of serious adverse events (SAEs) related to atezolizumab
treatment
•Incidence of immune-related adverse events (irAEs) related to
atezolizumab treatment. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At the end of the study. The end of study and final analysis will occur when all enrolled patients have either died, withdrawn consent, are lost to follow up, or have been followed for 30 months since the last study patient is enrolled, whichever occurs first. |
|
| E.5.2 | Secondary end point(s) |
•Overall survival (OS) rate at 2 years, defined as the proportion of patients remaining alive 2 years after initiation of study treatment
• OS, defined as the time from initiation of study treatment to death from any cause
• Progression-free survival (PFS), defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) and also by disease status evaluated by the investigator according to modified RECIST
• OS rate at 3 years, defined as the proportion of patients remaining alive 3 years after initiation of study treatment
• Objective response rate (ORR), defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1 and also by disease status evaluated by the investigator according to modified RECIST
• Duration of response (DOR), defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1 and also by disease status evaluated by the investigator according to modified RECIST
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At the end of the study. The end of study and final analysis will occur when all enrolled patients have either died, withdrawn consent, are lost to follow up, or have been followed for 30 months since the last study patient is enrolled, whichever occurs first. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| long-term safety & efficacy study of atezolizumab treatment in patients with Stage IIIb or IV NSCLC |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Brazil |
| China |
| Colombia |
| Costa Rica |
| Guatemala |
| Lebanon |
| Malaysia |
| Mexico |
| Morocco |
| Panama |
| Peru |
| Philippines |
| United Arab Emirates |
| Denmark |
| Greece |
| Italy |
| Latvia |
| Netherlands |
| Slovenia |
| Sweden |
| United Kingdom |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study and final analysis will occur when all enrolled patients have either died, withdrawn consent, are lost to follow up, or have been followed for 30 months since the last study patient is enrolled, whichever occurs first.
The primary analysis will occur approximately 6 months after the last
patient has been enrolled. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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