E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with advanced non-small cell lung cancer and malignant pleural mesothelioma, positive for PD-L1 expression and germ or somatic mutations in DNA damage repair genes |
pazienti con carcinoma polmonare non a piccole cellule avanzato e mesotelioma pleurico maligno, positivo per espressione di PD-L1 e mutazioni germinali o somatiche nei geni di riparo del danno al DNA |
|
E.1.1.1 | Medical condition in easily understood language |
patients with advanced non-small cell lung cancer and malignant pleural mesothelioma, positive for PD-L1 expression and germ or somatic mutations in DNA damage repair genes |
pazienti con carcinoma polmonare non a piccole cellule avanzato e mesotelioma pleurico maligno, positivo per espressione di PD-L1 e mutazioni germinali o somatiche nei geni di riparo del danno al DNA |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062042 |
E.1.2 | Term | Lung neoplasm |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045155 |
E.1.2 | Term | Tumor of pleura |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 progression free survival (PFS) |
Sopravvivenza libera da progressione |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the objective response rate (ORR) To evaluate the duration of response (DOR) To evaluate the disease control rate (DCR) To evaluate the overall survival (OS) To evaluate the safety and tolerability of the combination of Niraparib and dostarlimab |
Tasso di risposte obiettive; durata delle risposte obiettive; tasso di controllo di malattia; sopravvivenza globale; tollerabilità |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Diagnosis (cyto or histological) of Mesothelioma or non-small cell lung cancer EGFR / ALK / ROS1 in advanced wild type - Disease progression to at least one previous systemic therapy line - Presence of germline and / or somatic mutations in DNA shelter genes and PD-L1 expression = 1% - Informed consent - Age over 18 and under 75 - Disease measurable according to RECIST criteria - Consent to biological material analysis (tissue biopsy) - Performance status 0-1 - Adequate organ functions |
- Diagnosi (cito o istologica) di Mesotelioma o Tumore polmonare non a piccole cellule EGFR/ALK/ROS1 wild-type in stadio avanzato - Progressione di malattia ad almeno una precedente linea di terapia sistemica - Presenza di mutazioni germinali e/o somatiche nei geni del riparo DNA ed espressione del PD-L1 = 1% - Consenso informato - Età maggiore di 18 anni e minore di 75 anni - Malattia misurabile secondo criteri RECIST - Consenso ad analisi materiale biologico (biopsia tissutale) - Performance status 0-1 - Adeguate funzioni d’organo |
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E.4 | Principal exclusion criteria |
- Participation in other clinical studies - Presence of EGFR gene sensitizing mutations or ALK / ROS1 rearrangements - Immunodeficiency diagnosis - History of tuberculous infection - Known hypersensitivity to Niraparib or Dostarlimab, or excipients - Previous diagnosis of myelodysplastic syndrome or acute myeloid leukemia - Other known malignancy requiring active treatment - Diagnosis of autoimmune diseases Current or past non-infectious pneumonia treated with steroids or evidence of interstitial lung disease - Symptomatic cerebral or leptomeningeal metastases - Known medical conditions that may in some way preclude participation in the study because they confuse the results of the study itself or interfere with the participation of the subject, at the discretion of the researchers involved - Psychiatric comorbidities that preclude participation in the study / informed consent - Pregnancy / breastfeeding - Previous therapy with PARP inhibitors (poly-adenosine diphosphate-ribose) - Previous therapy with anti PD-1 or PD-L1 agents - HIV infection - Hepatitis B infection - Vaccinations within 30 days from the start of the experimental treatment |
- Partecipazione ad altri studi clinici - Presenza di mutazioni sensibilizzanti gene EGFR o riarrangiamenti ALK/ROS1 - Diagnosi di immunodeficienza - Anamnesi di infezione tubercolare - Ipersensibilità nota a Niraparib o Dostarlimab, o eccipienti - Pregressa diagnosi di sindrome mielodisplastica o leucemia mieloide acuta - Altra neoplasia nota che richieda trattamento attivo - Diagnosi di malattie autoimmuni - Polmonite non infettiva in atto o pregressa trattata con steroidi o evidenza di malattia interstiziale del polmone - Metastasi cerebrali o leptomeningee sintomatiche - Note condizioni mediche che possano in qualche modo precludere la partecipazione allo studio perché confondenti i risultati dello studio stesso o interferire con la partecipazione del soggetto, a discrezione dei ricercatori coinvolti - Comorbidità psichiatriche che precludano l’adesione allo studio/consenso informato - Gravidanza/allattamento - Precedente terapia con inibitori di PARP (poly-adenosine diphosphate-ribose) - Precedente terapia con agenti anti PD-1 o PD-L1 - Infezione HIV - Infezione epatite B - Vaccinazioni entro 30 giorni dall’inizio del trattamento sperimentale |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) |
Sopravvivenza libera da malattia |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
the time from the date of the first treatment dose until either disease progression |
il tempo che intercorre dalla data del primo trattamento fino a progressionedi malattia |
|
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 | No |
E.6.5 | Efficacy | No |
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 | 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) | 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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |