Dostarlimab + Niraparib for Penile Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Must not be taking: Immune suppressants, Steroids
Disqualifiers: Autoimmune disease, Active infection, Hepatitis, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
The purpose of the study is to evaluate the efficacy and safety of the combination of niraparib and dostarlimab in patients participants with advanced relapsed/refractory penile cancer.
Do I need to stop taking my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on chronic systemic steroids over 20 mg daily or have used an investigational agent recently. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination Dostarlimab and Niraparib for treating penile cancer?
Is the combination of Dostarlimab and Niraparib generally safe for humans?
The combination of Dostarlimab and Niraparib has been studied for safety in patients with various cancers, including ovarian and lung cancer. These studies aim to assess safety alongside effectiveness, indicating that the treatment is generally considered safe for human use, though specific side effects and risks should be discussed with a healthcare provider.12567
How is the drug combination of Dostarlimab and Niraparib unique for treating penile cancer?
The combination of Dostarlimab and Niraparib is unique because it combines a PD-1 inhibitor, which helps the immune system attack cancer cells, with a PARP inhibitor, which prevents cancer cells from repairing their DNA, potentially making them more vulnerable to treatment. This approach is novel for penile cancer, as there are no standard treatments specifically targeting this cancer type with these mechanisms.12356
Eligibility Criteria
This trial is for adults with advanced penile cancer that has returned or resisted treatment. They must have measurable disease, good organ function, and a life expectancy over 12 weeks. Only those who've had at most one prior therapy and no immune-oncology treatments can join. Participants need to agree to contraception use during the study.Inclusion Criteria
I have small, symptom-free brain metastases not needing steroids.
I've had only one prior treatment for my cancer that either didn't work or caused side effects.
I haven't taken more than 20 mg of steroids daily for the last 4 weeks.
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Exclusion Criteria
I have had lung inflammation or a related condition that needed steroids.
Use of an investigational agent or an investigational device within specified timeframe before administration of first dose of study drug
I had a severe reaction to previous immunotherapy, except for minor lab changes.
See 14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 500 mg Dostarlimab IV every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks, along with 200 mg Niraparib by mouth once daily days 1-21 of all cycles
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Treatment Details
Interventions
- Dostarlimab (PD-1 Inhibitor)
- Niraparib (PARP Inhibitor)
Trial OverviewThe trial tests combining two drugs, Dostarlimab and Niraparib, on patients with relapsed/refractory penile cancer. It aims to assess how effective and safe this combination is when other treatments haven't worked.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Dostarlimab and Niraparib treatmentExperimental Treatment2 Interventions
Participants will be given 500 mg Dostarlimab IV every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks, along with 200 mg Niraparib by mouth once daily days 1-21 of all cycles.
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:
MD Anderson Cancer CenterHouston, TX
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
GlaxoSmithKlineIndustry Sponsor
References
Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). [2023]This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRCA wild type (BRCAwt) recurrent platinum-resistant ovarian cancer (PROC) who had previously received bevacizumab treatment.
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.
Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. [2023]Niraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population.
Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). [2021]To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Dostarlimab: A Review. [2022]Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody for the treatment of adult patients, with mismatch repair deficient (dMMR), recurrent or advanced endometrial cancer that has progressed on or following prior therapy with a platinum-containing regimen. As determined by an FDA-approved test this indication was granted rapid approval based on the rate of tumor response and the duration of the response. Continued approval for this indication is conditioned on further confirmatory trials demonstrating and documenting clinical benefit. In June 2022, the clinical trial NCT04165772 reported a 100% remission rate for rectal cancer. This clinical trial brought proof that we can match a tumor and the genetics of what is driving it, with therapy. This clinical trial continues to enroll patient and is currently enrolling patients with gastric, prostate, and pancreatic cancers. Dostarlamib is being recommended for rectal cancer. The focus of this review is to summarize the existing knowledge regarding Dostarlimab and explore the possibilities of mono- and combination therapies.
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.
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.