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. | Cáncer de pulmón de células no pequeñas avanzado, Cáncer de pulmón de células no pequeñas metastásico, Cáncer de pulmón de células no pequeñas irresecable en estadio III, Cáncer de pulmón de células no pequeñas en estadio IV. | |
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. | Cáncer de pulmón de células no pequeñas, que está localizado pero es demasiado grande para ser extraído quirúrgicamente o que ya se ha extendido por todo el cuerpo. | |
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 | |
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. | Evaluar la seguridad, farmacocinética, farmacodinamia y eficacia de AZD2936 en participantes adultos con CPCNP en estadio III irresecable o estadio IV. | |
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. | Evaluar la inmunogenicidad de AZD2936 y la compatibilidad del perfil farmacocinético de AZD2936 en pacientes con experiencia en 2L + CPI y 1L CPI sin tratamiento previo con CPCNP irresecable en estadio III/IV. | |
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. | - Consentimiento informado firmado. - 18 años de edad, o mayor. - CPCNP irresecable en estadio III o escamoso o no escamoso en estadio IV no susceptible a cirugía curativa o radiación. - Expresión de PD-L1 documentada por PD-L1 IHC según informe local. - Progresión confirmada durante el tratamiento con un régimen que incluye CPI (Parte A, Parte B). - No hubo tratamiento previo (incluidos los agentes IO) para el CPCNP (solo la Parte C). - Estado funcional ECOG de 0 o 1 en el momento del reclutamiento. - Esperanza de vida ≥ 12 semanas en el momento del reclutamiento. - Función adecuada de la médula ósea, el hígado y los riñones. | |
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. | - Sensibilización de mutaciones en el receptor del factor de crecimiento epidérmico (EGFR) o fusión de la quinasa del linfoma anaplásico (ALK). - Resultado de prueba documentada para cualquier otra alteración genómica conocida para la cual hay terapia dirigida aprobada en primera línea según el estándar local de cuidados (por ejemplo, ROS1, fusiones NTRK, BRAF, mutación V600E) - Tratamiento previo con terapia anti-TIGIT. - Cualquier quimioterapia, radioterapia; terapia con fármaco en investigación, biológica u hormonal para el tratamiento contra el cáncer. - Resistencia primaria o secundaria después del tratamiento con 2 o más regímenes que incluyen un IPC. - Metástasis sintomática del sistema nervioso central (SNC). - Evento tromboembólico en los 3 meses anteriores al reclutamiento. - Otra neoplasia maligna invasiva en los 2 años anteriores al screening. | |
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: - 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 | Parte A: - Seguridad y tolerabilidad de AZD2936, evaluada por el porcentaje de pacientes con eventos adversos, eventos adversos inmunomediados y toxicidades limitantes de la dosis, así como la tasa de interrupción de AZD2936 debido a la toxicidad. Parte B: - Seguridad y tolerabilidad de AZD2936, evaluada por el porcentaje de pacientes con eventos adversos, eventos adversos inmunomediados y toxicidades limitantes de la dosis, así como la tasa de interrupción de AZD2936 debido a la toxicidad. - Actividad antitumoral preliminar de AZD2936, evaluada por objetivo tasa de respuesta (ORR) según RECIST 1.1 | |
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). | Seguridad: desde la firma del consentimiento informado hasta 90 días después de la última dosis de intervención del estudio. Eficacia: desde la primera dosis de la intervención del estudio hasta la progresión de la enfermedad o muerte (si no hay progresión de la enfermedad). | |
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. | Parte A: - Actividad antitumoral preliminar de AZD2936, evaluada por tasa de respuesta objetiva (ORR), tasa de control de enfermedad (DCR), duración de respuesta (DoR) y tasa de respuesta duradera (DRR) según RECIST 1.1. - Compromiso de objetivo de AZD2936 en sangre periférica, evaluado por TIGIT y ocupación del receptor PD-1 (RO) en células T de sangre periférica y células NK. Parte B: - Actividad antitumoral preliminar de AZD2936, evaluada por tasa de control de enfermedad (DCR), duración de la respuesta (DoR), tasa de respuesta duradera (RRD) y supervivencia libre de progresión (SLP) según RECIST 1.1. - Compromiso de objetivo de AZD2936 en sangre periférica, evaluado por TIGIT y ocupación del receptor PD-1 (RO) en células T de sangre periférica y células NK. | |
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). | Seguridad: desde el momento de la firma en consentimiento informado hasta 90 días después de la última dosis de intervención del estudio. Eficacia: desde la primera dosis de la intervención del estudio hasta la progresión de la enfermedad o muerte (si no hay progresión de la enfermedad). | |
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 | 3 |
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 | Germany | Italy | Netherlands | Poland | Spain | United Kingdom | |
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 | 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. | El final del estudio se define como la fecha de la última visita del último paciente en el estudio o el último procedimiento programado que se muestra en el SoA para el último paciente en el estudio a nivel mundial. | |
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 | 9 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |