E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non−small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable Stage III NSCLC is a lung cancer that is in the chest and cannot be surgically removed. |
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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 | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
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 evaluate the efficacy of atezolizumab in combination with tiragolumab compared with durvalumab in the intent to treat (ITT) and the programmed death-ligand 1 (PD-L1)-positive populations based on an independent review facility-assessed progression-free survival. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of atezolizumab plus tiragolumab compared with durvalumab in the ITT and the PD-L1-positive populations based on OS after randomization, Investigator -assessed progression-free survival, , time to death or distant metastasis, confirmed objective response rate, duration of response in patients with confirmed objective response rate, progression-free survival rate, OS rate, time to confirmed deterioration
• To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with placebo plus durvalumab
• To characterize pharmacokinetics of tiragolumab and atezolizumab
• To evaluate the immune response to tiragolumab plus atezolizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age>= 18 years
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Histologically or cytologically documented NSCLC with locally advanced unresectable Stage III NSCLC of either squamous or non-squamous histology
- Whole-body positron emission tomography (PET)-CT scan for the purposes of staging, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (CRT)
- At least two prior cycles of platinum-based chemotherapy concurrent with RT (CRT), which must be completed within 1 to 42 days prior to randomization in the study
- The RT component in the CRT must have been at a total dose of radiation of 60 Gy±10% (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or 3D-conforming technique
- No progression during or following concurrent platinum-based CRT
- Tumor PD-L1 expression, as determined by the investigational Ventana PD-L1 (SP263) CDx assay and documented by central testing of tissue collected prior to the first dose of cCRT
- Adequate hematologic and end-organ function. |
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E.4 | Principal exclusion criteria |
- Any history of prior NSCLC
- NSCLC known to have a mutation in the epidermal growth factor mutation and/or an anaplastic lymphoma kinase translocation
- Any evidence of Stage IV disease
- Treatment with sequential CRT for locally advanced NSCLC
- Patients with locally advanced NSCLC who have progressed during or after the definitive concurrent CRT prior to randomization
- Any Grade > 2 unresolved toxicity from previous CRT
- Grade >=2 pneumonitis from prior CRT
- Active or history of autoimmune disease or immune deficiency, history of idiopathic pulmonary fibrosis, organizing pneumonia
- History of malignancy other than NSCLC within 5 years prior to screening
- Prior allogeneic stem cell or solid organ transplantation
- Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies
- Any prior Grade >= 3 immune-mediated adverse event or any unresolved Grade > 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents
- Current treatment with anti-viral therapy for hepatitis B virus or hepatitis C virus
- Active EBV infection or known or suspected chronic active EBV infection at Screening
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-T-cell immunoreceptor with Ig and ITIM domains, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-[antiTNF-alpha]agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressivemedication during study treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Independent review facility-assessed Progression Free Survival in ITT and PD-L1 positive populations. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Overall survival
2. Investigator -assessed Progression Free Survival
3. Time to death or distant metastasis
4. Confirmed Objective response rate
5. Duration of Response in patients with confirmed ORR
6. Progression Free Survival rate at 12 months, 18 months, and 24 months
7. Overall Survival rate at 12 months, 24 months, 36 months, and 48 months
8. Time to confirmed deterioration
9. Incidence and severity of adverse events
10. Serum concentrations of tiragolumab and atezolizumab at specified timepoints
11. Prevalence and incidence of anti-drug antibodies (ADAs) to tiragolumab and atezolizumab at baseline and during the study. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to 90 months
6. At 12 months, 18 months, and 24 months
7. At 12 months, 24 months, 36 months, and 48 months
8-9. Up to 90 months
10 and 11. Day 1 of Cycle 1-4,8,10,12 and at treatment discontinuation or completion visit; for tiragolumab: Day 1 of cycle 3. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and Exploratory Biomarker |
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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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Russian Federation |
Spain |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
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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
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The end of study will occur when all of the following criteria have been met:
- The required number of deaths for the final analysis of OS has been observed
- The last patient, last visit has occurred.
In addition, the Sponsor may decide to terminate the study at any time. If the Sponsor decides to terminate the study, patients who are still receiving study treatment or undergoing survival follow-up may be enrolled in an extension study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 90 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 90 |