Combination treatment for advanced lung cancer and mesothelioma

A Phase II, Open-Label, Single Arm, Prospective, Multicenter Study of Niraparib Plus Dostarlimab in Patients With Advanced NSCLC and/or MPM, and Positive for PD-L1 Expression and Germline or Somatic Mutations in the HRR Genes

This study is testing a new combination of two drugs to see if it can help people with advanced lung cancer and mesothelioma who have certain genetic markers and have already received treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Turin, Italy (Academic / other)
• Drugs / interventions: dostarlimab, chemotherapy, immunotherapy, radiation, prednisone
• Locations: 1 site (Orbassano, Turin)
• Trial ID: NCT04940637 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness of a combination of niraparib and dostarlimab in patients with advanced non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) who have positive PD-L1 expression and mutations in DNA homologous recombination repair (HRR) genes. The study will enroll approximately 70 patients who have previously been treated and are not candidates for curative treatment. Participants will be grouped based on their HRR and PD-L1 status, and the trial aims to assess the safety and efficacy of the treatment combination.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced NSCLC or MPM who have previously received treatment and have specific genetic markers indicating HRR deficiency and PD-L1 positivity.

Not a fit: Patients without HRR mutations or those with negative PD-L1 expression may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced lung cancer and mesothelioma who currently have limited treatment options.

How similar studies have performed: While this approach is novel in this specific context, similar studies combining targeted therapies and immunotherapies have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

* Participant must have histological or cytological proven diagnosis of advanced (stage IV) NSCLC without known EGFR-sensitizing mutation or ALK/ROS1 rearrangements and/or histological or cytological proven diagnosis of advanced or metastatic MPM (according to the 8th Edition of the UICC TNM Classification).
* Participant must have experienced disease progression or recurrence during or after at least one systemic therapy for advanced metastatic disease:
* Participant must be able to provide adequate archival tumor tissue specimen for central somatic (s)HRd and PD-L1 status assessment, which may have been collected at any time prior to screening. If no archival FFPE tumor tissue is available, a newly obtained tissue biopsy is required before Cycle 1/Day 1.
* Participant must be able to provide adequate pre-treatment blood samples for central germline (g)HRd assessment.
* Participant must have centrally-confirmed positivity for germline or somatic HRd status and tumor PD-L1 expression (TPS ≥ 1%).
* Participant with NSCLC must have measurable disease by computed tomography (CT) scan as defined by RECIST v1.1: at least 1 tumor lesion ≥10 mm in the longest diameter, or a lymph node ≥15 mm in short axis measurement.
* Participant with MPM must have Evaluable disease or measurable disease as assessed according to the mRECIST v1.1
* Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
* Participant must be ≥ 18 years of age
* Participant must have adequate organ function
* Female participant has a negative urine or serum pregnancy test within 24-72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy and to perform a monthly pregnancy testing from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.
* Participant must agree to not breastfeed during the study or for 150 days after the last dose of study treatment.
* Male participant agrees to use an adequate method of contraception (see Section 4.4 for a list of acceptable birth control methods) starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
* Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Exclusion Criteria:

* Participant with current participation in any interventional clinical trial and/or Participant who received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
* Participant who received major surgery ≤3 weeks prior to initiating protocol therapy and/or has been recovered from any surgical effects.
* Participant who received last treatment ≥12 weeks from initiation of protocol therapy.
* Participant who received radiation therapy within 2 weeks prior to Day 1 of protocol therapy.
* Participant with known hypersensitivity to niraparib and dostarlimab components or excipients.
* Participant who received transfusion (platelets or red blood cells) ≤4 weeks prior to initiating protocol therapy.
* Participant who received colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
* Participant with any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
* Participant with any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
* Participant with a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
* Participant with diagnosis, detection, or treatment of another type of malignancy ≤2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
* Participant with known, symptomatic brain or leptomeningeal metastases.
* Patient who experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
* Participant with a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg of prednisone or equivalent daily) or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
* Participant with a known history of human immunodeficiency virus (type 1 or 2 antibodies).
* Participant with a known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[qualitative\] is detected).
* Participant with an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Participant with a known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment
* Participant has received a live vaccine within 14 days of initiating protocol therapy.
* Participant who received prior treatment with a PARP inhibitor
* Participant who is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for 180 days after the last dose of study treatment
* Male participant who is expecting to donate sperm or father children while receiving study drug or for 180 days after the last dose of study treatment

Where this trial is running

Orbassano, Turin

• AOU San Luigi- Department of Oncology — Orbassano, Turin, Italy (Recruiting)

Study contacts

• Principal investigator: Giorgio V Scagliotti, Medicine — Oncology department-University of Turin- AOU San Luigi Gonzaga
• Study coordinator: giorgio v scagliotti, medicine

Conditions Lung Cancer; Mesothelioma