This is a single arm, prospective, interventional, multicenter phase 2 study of the combination of niraparib and dostarlimab in patients with advanced non-small cell lung cancer (NSCLC) and/or malignant pleural mesothelioma (MPM), and positive for PD-L1 expression (TPS ≥ 1%) and germline or somatic mutations in the DNA homologous recombination repair (HRR) genes.
This is a single arm, prospective, interventional, multicenter phase 2 study of the combination of niraparib and dostarlimab in patients with advanced non-small cell lung cancer (NSCLC) and/or malignant pleural mesothelioma (MPM), and positive for PD-L1 expression (TPS ≥ 1%) and germline or somatic mutations in the DNA homologous recombination repair (HRR) genes. Approximately 70 eligible patients with previously treated advanced disease, not amenable for curative treatment will be included in this study and will be grouped as follows: * Homologous recombination deficiency (HRd)-positive and PD-L1-positive advanced NSCLC referred to as Cohort A (n= 35) * HRd-positive and PD-L1-positive advanced MPM referred to as Cohort B (n= 35) HRd-positive and PD-L1-positive are defined as follows: * HRd-positive: Tumors that harbor known or suspected deleterious germline or somatic mutations in the HRR genes, based on the HRd Assay. * PD-L1-positive: Tumors with PD-L1 expression on at least 1% of tumor cells based on immunohistochemistry (IHC) analysis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
niraparib 300 mg/die and dostarlimab 500 mg day 1 Q3 weeks for the first 4 cycles followed by 1000 mg day 1 Q6 weeks
AOU San Luigi- Department of Oncology
Orbassano, Turin, Italy
RECRUITINGPFS
the time from the date of the first treatment dose until either disease progression, as assessed by investigator's review according to RECIST v1.1criteria, or modified RECIST for assessment of response in malignant pleural mesothelioma version 1.1 (mRECIST v1.1), or death due to any cause, whichever occurs first.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Objective response rate
the proportion of participants who have a best overall response of either complete response (CR) or partial responses (PR) as assessed by investigator's review according to RECIST v1.1, or modified RECIST for assessment of response in malignant pleural mesothelioma version 1.1 (mRECIST
Time frame: up to 36 months
Disease control rate
the proportion of participants who have complete response (CR), partial responses (PR), or stable disease (SD) as assessed by investigator's review according to RECIST v1.1 or mRECIST v1.1
Time frame: up to 36 months
Duration of response
the time from the date a response was first documented until either disease progression or death due to any cause, whichever occurs first.
Time frame: up to 36 months
Overall survival
the time from the date of the first dose to death due to any cause
Time frame: up to 36 months
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