E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Stage III unresectable Non-small cell lung cancer (NSCLC), who have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and who are treated with radiotherapy but are ineligible for chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
A specific type of 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 | 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 assess the safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs within 6 months from the initiation of durvalumab treatment |
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E.2.2 | Secondary objectives of the trial |
-To assess the efficacy of durvalumab treatment in terms of PFS and OS -To further assess the efficacy of durvalumab treatment in terms of ORR and DoR -To assess the efficacy of durvalumab treatment in terms of lung cancer mortality -To further assess the safety and tolerability profile of durvalumab treatment, including all AEs |
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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 |
Genetic research.
Blood sample will also be taken to allow for future exploratory research of genes/genetic factors that may influence response of durvalumab. |
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E.3 | Principal inclusion criteria |
- Informed consent as detailed in the protocol. - 18 years or older at the time of signing the ICF. - Histologically-or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 [IASLC 2016]). (a) Imaging to rule out distant metastasis is required. (b) Endobronchial ultrasound with biopsy is encouraged in patients with suspected lymph node involvement. - Deemed ineligible for chemotherapy per Investigator assessment (eg, comorbidities, poor PS, etc). - Receipt of radiation therapy that was completed within 42 days prior to first IP dose administration in the study. - Patients must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED). Further details are provided in the protocol. - Patients must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria as defined in the protocol. - WHO/ECOG PS of ≤ 2. - No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines. - Adequate organ and marrow function as defined in the protocol. - Must have a life expectancy of at least 12 weeks. - Body weight > 30 kg at enrollment and first IP dose administration - Male or female |
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E.4 | Principal exclusion criteria |
- Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy. - Mixed small cell lung cancer and NSCLC histology. - History of allogeneic organ transplantation. - Active or prior documented autoimmune or inflammatory disorders as defined in the protocol. - Uncontrolled intercurrent illness as defined in the protocol. - History of another primary malignancy except for (1) Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of durvalumab and of low potential risk for recurrence (2) Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease (3) Adequately treated carcinoma in situ without evidence of disease. - History of leptomeningeal carcinomatosis - History of active primary immunodeficiency - Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies). - Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criteria -Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. -Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. - Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients Prior/concomitant therapy - Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. - Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab. - Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. Please refer to protocol for exceptions. - Participation in another clinical study with an IP administered in the last 4 weeks - Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study - Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment
Please refer to the protocol pages 38-39 for further criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Grade 3 and Grade 4 PRAEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 6 months after the initiation of durvalumab treatment. |
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E.5.2 | Secondary end point(s) |
Median PFS according to RECIST 1.1 as assessed by the Investigator PFS6 and PFS12 according to RECIST 1.1 as assessed by the Investigator Median OS and OS12 ORR according to RECIST 1.1 as assessed by the Investigator DoR according to RECIST 1.1 as assessed by the Investigator Lung cancer mortality AEs, SAEs, AESIs, imAEs, physical examinations, vital signs including BP, pulse, ECGs, and laboratory findings including clinical chemistry, hematology, and urinalysis |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Median PFS; proportion of patients progression-free at 6 and 12 months. Median OS; proportion of patients alive at 12 months. |
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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 | Yes |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
Patients will be enrolled into 2 cohorts according to the dose of radiotherapy received |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
France |
Italy |
Poland |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |