Niraparib + Dostarlimab for Brain Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: PARP inhibitors, PD-1/L1 inhibitors
Disqualifiers: Prostate cancer, Active hepatitis, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To learn if the combination of niraparib and dostarlimab can help to control advanced cancer that has spread to the brain.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you must not be receiving other interventional anticancer treatments at the same time. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination Niraparib and Dostarlimab for brain cancer?
Dostarlimab has been approved for treating certain types of endometrial cancer, showing it can be effective against some cancers. Niraparib has been studied for advanced breast cancer with specific genetic mutations, indicating it may help in treating cancers with similar characteristics.
12345How is the drug combination of Niraparib and Dostarlimab unique for brain cancer treatment?
The combination of Niraparib and Dostarlimab is unique because it targets cancer cells by exploiting their DNA repair weaknesses and enhancing the immune system's ability to fight cancer. Niraparib, a PARP inhibitor, increases DNA damage in cancer cells, while Dostarlimab, an immune checkpoint inhibitor, helps the immune system recognize and attack these damaged cells, offering a novel approach compared to traditional treatments.
24567Eligibility Criteria
Adults (18+) with advanced cancers that have spread to the brain, including specific types such as BRCA1/2m cancer and various lung and breast cancers. Participants must have had previous treatment, possess measurable brain metastasis not requiring immediate intervention or steroids, and adequate organ function. They cannot be pregnant or breastfeeding and must agree to contraception.Inclusion Criteria
I can take care of myself and am up and about more than half of my waking hours.
My organs are functioning well.
I am 18 years old or older.
+10 more
Exclusion Criteria
I cannot swallow pills or have a gut condition affecting medication absorption.
Participants with an inactive, known or suspected autoimmune disease
Participants unable to undergo contrast enhanced brain MRI
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive niraparib and dostarlimab to assess intracranial objective response rate and systemic antitumor activity
12 weeks
Follow-up
Participants are monitored for safety, tolerability, and effectiveness after treatment
8 weeks
Participant Groups
The trial is testing a combination of two drugs: Niraparib, a PARP inhibitor, and Dostarlimab, a PD-1 inhibitor. The goal is to see if these drugs can control advanced cancer in patients whose disease has progressed into the brain.
1Treatment groups
Experimental Treatment
Group I: MonotherapyExperimental Treatment2 Interventions
Dostarlimab is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Jemperli for:
- Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
- dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen
🇺🇸 Approved in United States as Jemperli for:
- Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
- Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. [2020]Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.
New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]The Food and Drug Administration (FDA) has granted accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors.
An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery-the BUMPER study. [2022]Patients with melanoma brain metastasis (MBM) still carry a dismal prognosis. Preclinical data originated in xenograft models showed that buparlisib therapy was highly effective in therapy-naïve MBM.
Dostarlimab: First Approval. [2021]Dostarlimab (Jemperli™; GlaxoSmithKline) is a humanized monoclonal antibody programmed death-1 (PD-1) receptor antagonist being developed for the treatment of various cancers. Based on preliminary results from the GARNET trial dostarlimab has recently been approved in the EU and USA for the treatment of adult patients with mismatch repair deficient recurrent or advanced endometrial cancer. This article summarizes the milestones in the development of dostarlimab leading to these first approvals.
Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study. [2023]Label="PURPOSE">To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer.
IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. [2022]Doublet combination therapies targeting immune checkpoints have shown promising efficacy in patients with advanced solid tumors, but it is unknown if rational triplet combinations will be well tolerated and associated with improved antitumor activity. The objective of this trial was to determine the recommended phase 2 doses (RP2Ds) and to assess the safety and efficacy of the programmed cell death protein 1 (PD-1) inhibitor dostarlimab in combination with (1) the poly(ADP-ribose) polymerase inhibitor niraparib with or without vascular endothelial growth factor inhibitor bevacizumab or (2) carboplatin-paclitaxel chemotherapy with or without bevacizumab, in patients with advanced cancer.
A Prospective Phase II Single-arm Study of Niraparib Plus Dostarlimab in Patients With Advanced Non-small-cell Lung Cancer and/or Malignant Pleural Mesothelioma, Positive for PD-L1 Expression and Germline or Somatic Mutations in the DNA Repair Genes: Rationale and Study Design. [2021]Treatment with poly ADP ribose polymerase (PARP)1/2 inhibitors represents a novel opportunity to selectively kill a subset of cancer cell types by exploiting their deficiencies in DNA repair, thus leading to synthetic lethality. Treatment of homologous recombination deficient (HRD)-tumors with PARP inhibitors generates significant levels of DNA damage, which has the potential to further increasing tumor mutational burden, promoting neoantigen release, and upregulating both interferons and programmed death ligand-1 (PD-L1) expression, suggesting a potential complementary and synergistic role with immune checkpoint inhibitors in cancer treatment. Here we present the design and rationale of a prospective, phase II, single-arm study aiming to investigate the safety and antitumor activity of the combination of niraparib and dostarlimab in patients with HRD-positive and PD-L1 ≥ 1% advanced non-small-cell lung cancer (NSCLC) and/or malignant pleural mesothelioma (MPM). Considering the prevalence of pathogenetic germline mutations in DNA repair genes, reported to be around 5% to 10% in patients with MPM and NSCLC, a total of 700 to 1000 cases will be screened to identify 70 patients who are HRD-positive/PD-L1 ≥ 1% (N = 35 NSCLC; N = 35 MPM) to be included. Patients will receive the combination of niraparib orally once daily and dostarlimab intravenously. The primary endpoint is progression-free survival. Secondary endpoints are objective response, duration of response, overall survival, and safety. The results of this study will provide evidence on the safety and antitumor activity of niraparib and dostarlimab combination in patients with advanced, HRD-positive and PD-L1 ≥ 1% NSCLC and/or MPM.