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A Phase II, Open-Label, Single Arm, prospective, multicenter study of niraparib plus dostarlimab in patients with advanced non-small cell lung cancer and malignant pleural mesothelioma, positive for PD-L1 expression and germline or somatic mutations in the DNA repair genes

Phase 1
Conditions
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
MedDRA version: 20.0Level: PTClassification code 10062042Term: Lung neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10045155Term: Tumor of pleuraSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2020-000109-10-IT
Lead Sponsor
DIPARTIMENTO DI ONCOLOGIA-UNIVERSITA' DEGLI STUDI DI TORINO
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
70
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate the progression free survival (PFS);Secondary Objective: To evaluate the objective response rate (ORR)<br>To evaluate the duration of response (DOR)<br>To evaluate the disease control rate (DCR)<br>To evaluate the overall survival (OS) <br>To evaluate the safety and tolerability of the combination of Niraparib and dostarlimab;Primary end point(s): Progression free survival (PFS);Timepoint(s) of evaluation of this end point: the time from the date of the first treatment dose until either disease progression
Secondary Outcome Measures
NameTimeMethod
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