E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small Cell Lung Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Non-small Cell Lung Cancer |
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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 | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 demonstrate improvement in PFS with M7824 compared with pembrolizumab.
To demonstrate improvement in OS with M7824 compared with pembrolizumab.
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E.2.2 | Secondary objectives of the trial |
Safety
-To evaluate the safety and tolerability of M7824 compared with pembrolizumab
Efficacy
-To evaluate the objective response of M7824 compared with pembrolizumab
-To evaluate the DOR of M7824 compared with pembrolizumab
PK
-To characterize pharmacokinetic (PK) profile of M7824
Immunogenicity
-To characterize the immunogenicity of M7824 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥ 18 years of age inclusive, at the time of signing the informed consent
2. histologically confirmed diagnosis of advanced NSCLC and:
a. Have not received prior systemic therapy treatment for their advanced/Stage IV
NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy,
and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy
was completed at least 6 months prior to the diagnosis of metastatic disease.
Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant
chemotherapy therapy to Grade ≤ 1. For radiation toxicity or prior major surgeries,
participants should have recovered from side effects and/or complications.
b. Have measurable disease based on RECIST 1.1
c. Have a life expectancy of at least 3 months
d. Availability of tumor tissue (< 6 months old, excluding bone biopsies) before the first dose is mandatory
to determine PD-L1 expression level prior to enrollment
e. PD-L1 high status by central testing is required
(other protocol defined criteria could apply) |
|
E.4 | Principal exclusion criteria |
1. Participants with nonsquamous NSCLC histologies whose tumor harbors any of the following molecular alterations and targeted therapy is locally approved:
a. EGFR sensitizing (activating) mutation
b. ALK translocation(s) associated with responsiveness to ALK tyrosine
kinase inhibitors
c. ROS1 rearrangement(s) associated with responsiveness to ROS1
tyrosine kinase inhibitors
d. BRAF V600E mutation
2. Has received major surgery within 4 weeks prior to the first dose of study intervention;
received thoracic RT of > 30 Gy within 6 months prior to the first dose of study
7. Known severe hypersensitivity reactions (Grade ≥ 3 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0) to
investigational product (M7824 or pembrolizumab) or any components in their formulations, or uncontrolled asthma (ie, 3 or more features of partially
controlled asthma)
8. Receipt of any organ transplantation
9. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required
oral or IV steroids
10. Significant acute or chronic infections
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with participation for the full
duration of the study, or is not in the best interest of the participant, in the opinion of the
treating Investigator. Participants with history of bleeding diathesis or recent
major bleeding events considered by the Investigator as high risk for
investigational drug treatment, such as patients with clinically relevant bleeding events of hemoptysis ≥ Grade 2 within the last month, are also excluded
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways)
intervention.
13. Previous malignant disease
14. Has active CNS metastases causing clinical symptoms or metastases that require
therapeutic intervention and/or carcinomatosis meningitis
15. Active autoimmune disease that has required systemic treatment in past 1 year OR is
receiving systemic steroid therapy < 3 days prior to the first dose of study intervention or
receiving any other form of immunosuppressive medication.
16. Is expected to require any other form of systemic or localized antineoplastic therapy
while on study (including maintenance therapy with another agent for NSCLC, RT,
and/or surgical resection)
(other protocol defined criteria could apply) |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) PFS according to RECIST 1.1 assessed by IRC
2) OS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from randomization to planned final assessment
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E.5.2 | Secondary end point(s) |
1) Occurrence of TEAEs and treatment-related AEs
2) OR according to RECIST 1.1 assessed by IRC
3) DOR assessed from CR or PR according to RECIST 1.1 assessed by IRC until PD, death, or last tumor assessment
4) PK profile of M7824 in terms of Ceoi
5) PK profile of M7824 in terms of Ctrough
6) Immunogenicity as measured by ADA assays at Baseline and ontreatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time from randomization to planned final assessment
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
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 |
Australia |
Canada |
Japan |
United States |
European Union |
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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 the study is defined as the data cut off date for the primary OS analysis when the planned number of deaths had been reported. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |