Niraparib + Dostarlimab for Breast Cancer

Recruiting at 8 trial locations

Overseen By Erica L. Mayer, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Stage IV breast cancer, Prior treatment, Immunodeficiency, Autoimmune disease, 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: 9

Duration: 18 weeks

62 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications that interact with the study drugs or are part of an investigational therapy, you may need to stop them. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination of Niraparib and Dostarlimab for breast cancer?

Niraparib has shown activity in patients with advanced breast cancer with specific genetic mutations (BRCA1/2), and Dostarlimab has been effective in treating certain types of endometrial cancer and other solid tumors. Additionally, a study on ovarian cancer showed that the combination of Niraparib and Dostarlimab was effective in patients who had previously received other treatments. ^{1 2 3 4 5}

Is the combination of Niraparib and Dostarlimab safe for humans?

Dostarlimab has been approved for certain cancers and has shown a good safety profile in trials, while Niraparib has been studied in breast cancer patients without new safety concerns. Both drugs have been used in humans, suggesting they are generally safe, but specific safety data for their combination in breast cancer is not detailed in the available research. ^{1 2 4 6 7}

What makes the drug combination of Niraparib and Dostarlimab unique for breast cancer treatment?

The combination of Niraparib and Dostarlimab is unique because it targets specific genetic mutations in breast cancer, such as BRCA1/2 mutations and mismatch repair deficiencies, which are not typically addressed by standard treatments. Niraparib is a PARP inhibitor that helps prevent cancer cells from repairing themselves, while Dostarlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. ^{1 2 3 4 7}

What is the purpose of this trial?

This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations. The names of the study drugs involved in this study are: * Niraparib (Zejula) * Dostarlimab

Research Team

Erica L. Mayer, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with Stage I to III breast cancer who have a BRCA1, BRCA2, or PALB2 mutation. They must be able to take oral medication and have no history of treatment for their current breast cancer. Individuals with severe health issues like heart disease, uncontrolled infections, or recent major surgery are not eligible.

Inclusion Criteria

Ability to understand and willingness to sign an informed consent document

My cancer is ER and PR positive and HER2 negative, tested in a certified lab.

My organs and bone marrow are functioning well.

Exclusion Criteria

I am allergic to medications similar to niraparib or dostarlimab.

You have an autoimmune disease that needed strong medication in the last 2 years.

I have received treatments like chemotherapy or radiation for my current breast cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Niraparib and Dostarlimab as pre-operative therapy for 18 weeks

18 weeks

6 visits (in-person) every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Long-term follow-up

Participants are monitored for long-term safety and outcomes

up to 5 years

Treatment Details

Interventions

• Dostarlimab
• Niraparib

Trial Overview The study tests pre-operative therapy using Niraparib (Zejula) and Dostarlimab in individuals with specific genetic mutations linked to breast cancer. It aims to see how well these drugs work before any surgical intervention.

Participant Groups

Group I: Arm C ER+/HER2- Experimental Treatment 2 Interventions

exploratory cohort of estrogen receptor (ER) positive HER2-negative participants will be enrolled to Arm C. * Niraparib Daily beginning with week 1, day 1 * Dostarlimab Once every three weeks beginning with week 1, day 1

Group II: Arm B TNBC Experimental Treatment 2 Interventions

Participants will be randomized 1:1 to treatment with the combination (Arm B) * 3-week lead-in of niraparib monotherapy followed by treatment with the combination * Niraparib Daily beginning with week 1, day 1 * Dostarlimab Once every three weeks beginning with week 4, day 1

Group III: Arm A Triple Negative Breast Cancer (TNBC) Experimental Treatment 2 Interventions

Participants will be randomized 1:1 to treatment with the combination (Arm A) * Niraparib-Daily beginning with week 1, day 1 * Dostarlimab-Once every three weeks beginning with week 1, day 1

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

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]

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]

In a phase III trial involving patients with advanced breast cancer and germline BRCA1/2 mutations, niraparib showed a median progression-free survival (PFS) of 4.1 months compared to 3.1 months for physician's choice chemotherapy, although the difference was not statistically significant (P = 0.86).

Despite the trial being halted due to issues with data assessment, niraparib demonstrated a 35% objective response rate, indicating its potential effectiveness in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Turner, NC., Balmaña, J., Poncet, C., et al.[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 (Zejula) is effective for treating recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, providing a targeted therapy option for these specific cancer types.

Ocrelizumab (Ocrevus) has shown efficacy in managing both relapsing and primary progressive multiple sclerosis, while dupilumab (Dupixent) is effective for patients with moderate-to-severe atopic dermatitis, highlighting its role in managing chronic inflammatory skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

In a pilot study of 21 patients with localized HER2-negative, BRCA-mutated breast cancer, neoadjuvant treatment with niraparib showed a high tumor response rate of 90.5% after 2 cycles, indicating strong antitumor activity.

Among those who continued treatment for 2-6 cycles, 40% achieved a pathological complete response, and no new safety concerns were reported, suggesting that niraparib is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. Spring, LM., Han, H., Liu, MC., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

5. United States 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). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. [2022]