E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Non-small Cell Lung Cancer, Metastatic Non-small Cell Lung Cancer, stage III unresectable Non-small Cell Lung Cancer, stage IV Non-small Cell Lung Cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Non-small Cell Lung Cancer, which is either localized but too big to be removed by surgery or has already spread throughout the body. |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080083 |
E.1.2 | Term | Advanced lung cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Evaluate the safety, PK, pharmacodynamics, and efficacy of AZD2936 in adult participants with stage III unresectable or stage IV NSCLC. |
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E.2.2 | Secondary objectives of the trial |
To assess the immunogenicity of AZD2936 and to assess the PK profile compatibility of AZD2936 in 2L+ CPI experienced and 1L CPI naïve participants with stage III/IV unresectable NSCLC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent - Aged 18 or above - Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. - Documented PD-L1 expression by PD-L1 IHC per local report. - Confirmed progression during treatment with a CPI-including regimen (Part A, Part B). - No prior treatment (including IO agents) for NSCLC (Part C only). - ECOG performance status of 0 or 1 at enrolment. - Life expectancy of ≥ 12 weeks at enrolment. - Adequate bone marrow, liver and kidney function. |
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E.4 | Principal exclusion criteria |
- Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusion. - Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions, BRAF, V600E mutation) - Previous treatment with an anti-TIGIT therapy. - Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. - Primary or secondary resistance after treatment with 2 or more regimens including a CPI. - Symptomatic central nervous system (CNS) metastasis. - Thromboembolic event within 3 months prior to enrolment. - Other invasive malignancy within 2 years prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A: - Safety and tolerability of AZD2936, assessed by the percentage of patients with adverse events, immune-mediated adverse events and dose-limiting toxicities as well as the rate of discontinuation of AZD2936 due to toxicity.
Part B and Part C: - Safety and tolerability of AZD2936, assessed by the percentage of patients with adverse events, immune-mediated adverse events and dose-limiting toxicities as well as the rate of discontinuation of AZD2936 due to toxicity. - Preliminary anti-tumour activity of AZD2936, assessed by objective response rate (ORR) according to RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety: from time of informed consent until 90 days after the last dose of study intervention. Efficacy: from first dose of study intervention to progressive disease or death (in absence of disease progression). |
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E.5.2 | Secondary end point(s) |
Part A: - Preliminary anti-tumour activity of AZD2936, assessed by objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and durable response rate (DRR) according to RECIST 1.1 - Target engagement of AZD2936 in peripheral blood, assessed by TIGIT and PD-1 receptor occupancy (RO) on peripheral blood T cells and NK cells.
Part B: - Preliminary anti-tumour activity of AZD2936, assessed by disease control rate (DCR), duration of response (DoR), durable response rate (DRR) and progression-free survival (PFS) according to RECIST 1.1 - Target engagement of AZD2936 in peripheral blood, assessed by TIGIT and PD-1 receptor occupancy (RO) on peripheral blood T cells and NK cells
Part C: - Preliminary anti-tumour activity of AZD2936, assessed by disease control rate (DCR), duration of response (DoR), durable response rate (DRR) and progression-free survival (PFS) according to RECIST 1.1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety: from time of informed consent until 90 days after the last dose of study intervention. Efficacy: from first dose of study intervention to progressive disease or death (in absence of disease progression). |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | No |
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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
China |
Japan |
Korea, Republic of |
United States |
Belgium |
Denmark |
France |
Poland |
United Kingdom |
Netherlands |
Spain |
Germany |
Italy |
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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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The end of the study is defined as the date of the last visit of the last participant in the study or last scheduled procedure shown in the SoA for the last participant in the study globally. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |