Dostarlimab + Niraparib for Penile Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with advanced penile cancer unresponsive to previous therapies. It combines two drugs, dostarlimab (an immunotherapy) and niraparib (a PARP inhibitor), to evaluate their combined effectiveness against cancer. The trial seeks participants with confirmed stage III or IV penile cancer who have not previously received certain immune therapies. Those who have experienced issues with other treatments or have recurrent cancer may find this trial suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of dostarlimab and niraparib is being tested for safety in treating advanced penile cancer. Earlier studies suggest that this combination can help the immune system fight tumors more effectively.

These treatments have been tested together in people with similar conditions, and many patients have tolerated the treatment well. However, like any treatment, side effects can occur. Some people have experienced nausea, tiredness, and low blood counts. These effects are common with cancer treatments, so discussing any concerns with a doctor is important.

Since this study is in an early stage, researchers are still gathering information to better understand the treatment's safety. While there's more to learn, the initial results are promising. Always consult a healthcare provider about the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dostarlimab and Niraparib for penile cancer because they bring a new approach to treatment. Unlike traditional chemotherapy and radiation, Dostarlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Niraparib, on the other hand, is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to their death. This combination of targeting the immune system and disrupting cancer cell repair mechanisms offers a promising alternative to existing options.

What evidence suggests that the combination of Dostarlimab and Niraparib could be effective for penile cancer?

This trial will evaluate the combination of dostarlimab and niraparib for treating advanced penile cancer. Studies have shown that using these drugs together can help the immune system attack tumors in patients who haven't responded to cisplatin. This combination might be more effective at destroying cancer cells than using each drug alone. Research also indicates that these drugs can enhance the body's ability to fight cancer. While more information is needed, early results are promising for those with difficult-to-treat penile cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Juskaran Chadha, DO

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

I have had lung inflammation or a related condition that needed steroids.

I had a severe reaction to previous immunotherapy, except for minor lab changes.

Use of an investigational agent or an investigational device within specified timeframe before administration of first dose of study drug

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• Niraparib

Trial Overview The 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.

How Is the Trial Designed?

Group I: Dostarlimab and Niraparib treatment Experimental Treatment 2 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

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Niraparib (NIRA) is an effective treatment for patients with metastatic castration-resistant prostate cancer who have specific genetic alterations, showing promising results in a Phase II study.

When combined with abiraterone acetate and prednisone, NIRA demonstrated a manageable safety profile while effectively disrupting cancer cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. Chi, KN., Fleshner, N., Chiuri, VE., et al.[2023]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

The combination treatment of dostarlimab and niraparib in patients with recurrent platinum-resistant ovarian cancer showed a low objective response rate of only 7.3%, leading to the early termination of the study due to insufficient efficacy.

Despite the treatment being generally safe with no new safety issues identified, 95.1% of patients experienced treatment-related adverse events, and health-related quality of life worsened over time, indicating a need for more effective therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Randall, LM., O'Malley, DM., Monk, BJ., et al.[2023]

Niraparib at a dose of 200 mg/day was determined to be the recommended phase 2 dose when combined with abiraterone acetate plus prednisone (AAP) for patients with metastatic castration-resistant prostate cancer (mCRPC), as it showed a tolerable safety profile with no new safety signals.

The combination of niraparib with apalutamide resulted in a higher incidence of dose-limiting toxicities, leading to the decision not to further evaluate this combination, highlighting the importance of monitoring drug interactions in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Saad, F., Chi, KN., Shore, ND., et al.[2021]

The study investigates the safety and effectiveness of combining niraparib, a PARP inhibitor, with dostarlimab, an immune checkpoint inhibitor, in treating advanced non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) in patients with homologous recombination deficiency (HRD) and PD-L1 expression of 1% or higher.

A total of 700 to 1000 patients will be screened to find 70 eligible participants, with the primary goal of assessing progression-free survival, while also evaluating overall survival and safety, highlighting the potential for this combination therapy to enhance cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Passiglia, F., Bironzo, P., Righi, L., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40377969/

Phase II Study Evaluating the Efficacy of Niraparib and ... We designed a single arm, open label, Phase II clinical trial to evaluate the combination of niraparib and dostarlimab in patients with R/M HNSCC.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05526989

Study of the Combination Dostarlimab With Niraparib In ... 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/ ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS14

A phase II trial of dostarlimab and niraparib combination ... The combination of niraparib and dostarlimab holds promise in eliciting a robust antitumor immune response in patients with cisplatin-refractory PSCC.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS13

A phase 2 study of the combination dostarlimab with ... This is an open-label, multi-center, Simon 2 stage design, phase 2 study to evaluate the efficacy and safety of the combination of niraparib and dostarlimab

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10138

Dostarlimab in Combination with Niraparib for the ... Giving dostarlimab in combination with niraparib may kill more cancer cells in patients with stage III-IV penile cancer than giving either drug alone.

6. researchgate.net researchgate.net/publication/397062045_Phase_2_study_of_dostarlimab_plus_niraparib_in_stage_III-IV_recurrent_or_refractory_Penile_squamous_cell_carcinoma?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJqb3VybmFsIiwicHJldmlvdXNQYWdlIjpudWxsLCJzdWJQYWdlIjoib3ZlcnZpZXcifX0

Phase 2 study of dostarlimab plus niraparib in stage III-IV ... We report a case of a 49-year-old male with penile squamous cell carcinoma, who initially presented with a penile lesion but became lost to ...